Trial Outcomes & Findings for Study of the Safety, Pharmacodynamics, Efficacy, and PK of TIMP-GLIA in Subjects With Celiac Disease (NCT NCT03738475)

Last Updated: 2020-08-12

Results Overview

The spots formed by interferon-gamma-secreting T-cells were counted with an automated ELISPOT analyzer. The average spot-forming units (SFU) per antigen was calculated. A response was considered positive when the average SFU in wells with a given peptide was at least twice that of the average SFU in the no-peptide control wells. Baseline (Day 15/Day 1) was defined as Day 15 (or Day 1 if enough blood was not available on Day 15). Peripheral blood mononuclear cell is PBMC.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

34 participants

Primary outcome timeframe

Baseline (Day 15/Day 1), Day 20

Results posted on

2020-08-12

Participant Flow

Participants took part in the study at 6 investigative sites in the United States from 11 November 2018 to 22 July 2019.

Participants diagnosed with celiac disease (CD) were enrolled in a 1:1 ratio in one of two treatment groups: Tolerogenic Immune Modifying Particles - Gliadin (TIMP-GLIA) or Placebo.

Participant milestones

Participant milestones
Measure	TIMP-GLIA 8 mg/kg TIMP-GLIA 8 milligram per kilogram (mg/kg), infusion, intravenously, once on Days 1 and 8.	Placebo TIMP-GLIA placebo-matching infusion, intravenously, once on Days 1 and 8.
Overall Study STARTED	16	18
Overall Study COMPLETED	15	18
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	TIMP-GLIA 8 mg/kg TIMP-GLIA 8 milligram per kilogram (mg/kg), infusion, intravenously, once on Days 1 and 8.	Placebo TIMP-GLIA placebo-matching infusion, intravenously, once on Days 1 and 8.
Overall Study Participant Non-Compliance	1	0

Baseline Characteristics

Study of the Safety, Pharmacodynamics, Efficacy, and PK of TIMP-GLIA in Subjects With Celiac Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	TIMP-GLIA 8 mg/kg n=16 Participants TIMP-GLIA 8 mg/kg, infusion, intravenously, once on Days 1 and 8.	Placebo n=18 Participants TIMP-GLIA placebo-matching infusion, intravenously, once on Days 1 and 8.	Total n=34 Participants Total of all reporting groups
Age, Continuous	44.6 years STANDARD_DEVIATION 13.47 • n=99 Participants	42.2 years STANDARD_DEVIATION 16.71 • n=107 Participants	43.3 years STANDARD_DEVIATION 15.09 • n=206 Participants
Sex: Female, Male Female	13 Participants n=99 Participants	15 Participants n=107 Participants	28 Participants n=206 Participants
Sex: Female, Male Male	3 Participants n=99 Participants	3 Participants n=107 Participants	6 Participants n=206 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	15 Participants n=99 Participants	18 Participants n=107 Participants	33 Participants n=206 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Asian	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Black or African American	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) White	16 Participants n=99 Participants	18 Participants n=107 Participants	34 Participants n=206 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Region of Enrollment United States	16 Participants n=99 Participants	18 Participants n=107 Participants	34 Participants n=206 Participants
Body Mass Index (BMI)	28.213 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 4.8479 • n=99 Participants	27.100 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 4.8214 • n=107 Participants	27.624 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 4.7933 • n=206 Participants
Disease Duration	9.30 years n=99 Participants	8.45 years n=107 Participants	8.95 years n=206 Participants
Gluten Free Diet Duration	111.10 months n=99 Participants	113.45 months n=107 Participants	111.10 months n=206 Participants

PRIMARY outcome

Timeframe: Baseline (Day 15/Day 1), Day 20

Population: The pharmacodynamic population included all randomized participants who received two doses of study medication, completed at least the first 3 days of the gluten challenge (12 grams per day \[g/day\] for 3 days), and had pharmacodynamic results on Study Days 1, 15, and 20.

Outcome measures

Outcome measures
Measure	TIMP-GLIA 8 mg/kg n=13 Participants TIMP-GLIA 8 mg/kg, infusion, intravenously, once on Days 1 and 8.	Placebo n=16 Participants TIMP-GLIA placebo-matching infusion, intravenously, once on Days 1 and 8.
Change From Baseline in Interferon-Gamma Spot Forming Units (IFN-gamma SFUs) in a Gliadin-specific Enzyme-linked Immunospot (ELISpot) at Day 20 Baseline (Day 15/Day 1)	3.08 SFUs/10^6 cells PBMC Standard Deviation 5.263	1.98 SFUs/10^6 cells PBMC Standard Deviation 3.184
Change From Baseline in Interferon-Gamma Spot Forming Units (IFN-gamma SFUs) in a Gliadin-specific Enzyme-linked Immunospot (ELISpot) at Day 20 Change at Day 20	2.01 SFUs/10^6 cells PBMC Standard Deviation 6.958	17.57 SFUs/10^6 cells PBMC Standard Deviation 25.283

SECONDARY outcome

Timeframe: Baseline (Day 15/Day 1), Day 20

Population: The pharmacodynamic population included all randomized participants who received two doses of study medication, completed at least the first 3 days of the gluten challenge (12 g/day for 3 days), and had pharmacodynamic results on Study Days 1, 15, and 20. Participants evaluable for this measure at given time point were included for the assessment.

Gliadin-specific T cell proliferation was determined by ELISA test. Baseline (Day 15/Day 1) was defined as Day 15 (or Day 1 if enough blood was not available on Day 15).

Outcome measures

Outcome measures
Measure	TIMP-GLIA 8 mg/kg n=13 Participants TIMP-GLIA 8 mg/kg, infusion, intravenously, once on Days 1 and 8.	Placebo n=16 Participants TIMP-GLIA placebo-matching infusion, intravenously, once on Days 1 and 8.
Change From Baseline in Gliadin-specific T Cell Proliferation by Enzyme-linked Immunosorbent Assay (ELISA) at Day 20 Change at Day 20	0.05 picogram per milliliter (pg/mL) Standard Deviation 0.284	0.00 picogram per milliliter (pg/mL) Standard Deviation 0.180
Change From Baseline in Gliadin-specific T Cell Proliferation by Enzyme-linked Immunosorbent Assay (ELISA) at Day 20 Baseline (Day 15/Day 1)	0.87 picogram per milliliter (pg/mL) Standard Deviation 0.275	1.00 picogram per milliliter (pg/mL) Standard Deviation 0.178

SECONDARY outcome

Timeframe: Baseline (Day 15/Day 1), Day 20

Population: The pharmacodynamic population included all randomized participants who received two doses of study medication, completed at least the first 3 days of the gluten challenge (12 g/day for 3 days), and had pharmacodynamic results on Study Days 1, 15, and 20. Participants evaluable for this measure at given time point were included for the assessment.

Gliadin-specific T Cell cytokine secretion was determined by ELISA test. Gliadin-specific cytokine included interferon gamma (IFN-γ), interleukin (IL) 1-beta (1-β), IL-10, IL-12, IL-13, IL-2, IL-4, IL-6, IL-8, tumor necrosis factor alpha (TNF-α). Baseline (Day 15/Day 1) was defined as Day 15 (or Day 1 if enough blood was not available on Day 15). A negative change from baseline value was reported when the observed sample response was less than the observed background response.

Outcome measures

Outcome measures
Measure	TIMP-GLIA 8 mg/kg n=13 Participants TIMP-GLIA 8 mg/kg, infusion, intravenously, once on Days 1 and 8.	Placebo n=16 Participants TIMP-GLIA placebo-matching infusion, intravenously, once on Days 1 and 8.
Change From Baseline in Gliadin-specific T Cell Cytokine Secretion by ELISA at Day 20 Baseline (Day 15/Day 1): IFN-γ	1.44 pg/mL Standard Deviation 2.727	1.70 pg/mL Standard Deviation 4.251
Change From Baseline in Gliadin-specific T Cell Cytokine Secretion by ELISA at Day 20 Change at Day 20: IFN-γ	-0.43 pg/mL Standard Deviation 2.044	-0.01 pg/mL Standard Deviation 2.149
Change From Baseline in Gliadin-specific T Cell Cytokine Secretion by ELISA at Day 20 Baseline (Day 15/Day 1): IL1-β	1.24 pg/mL Standard Deviation 1.507	2.68 pg/mL Standard Deviation 4.548
Change From Baseline in Gliadin-specific T Cell Cytokine Secretion by ELISA at Day 20 Change at Day 20: IL1-β	0.00 pg/mL Standard Deviation 1.456	-0.12 pg/mL Standard Deviation 5.946
Change From Baseline in Gliadin-specific T Cell Cytokine Secretion by ELISA at Day 20 Baseline (Day 15/Day 1): IL-10	0.42 pg/mL Standard Deviation 0.688	0.80 pg/mL Standard Deviation 1.135
Change From Baseline in Gliadin-specific T Cell Cytokine Secretion by ELISA at Day 20 Change at Day 20 :IL-10	0.53 pg/mL Standard Deviation 0.754	-0.21 pg/mL Standard Deviation 1.302
Change From Baseline in Gliadin-specific T Cell Cytokine Secretion by ELISA at Day 20 Baseline (Day 15/Day 1): IL-12	0.23 pg/mL Standard Deviation 0.727	-0.03 pg/mL Standard Deviation 0.755
Change From Baseline in Gliadin-specific T Cell Cytokine Secretion by ELISA at Day 20 Change at Day 20: IL-12	-0.01 pg/mL Standard Deviation 0.616	0.13 pg/mL Standard Deviation 0.548
Change From Baseline in Gliadin-specific T Cell Cytokine Secretion by ELISA at Day 20 Baseline (Day 15/Day 1): IL-13	2.23 pg/mL Standard Deviation 2.831	0.94 pg/mL Standard Deviation 3.504
Change From Baseline in Gliadin-specific T Cell Cytokine Secretion by ELISA at Day 20 Change at Day 20: IL-13	-2.06 pg/mL Standard Deviation 5.700	0.36 pg/mL Standard Deviation 1.655
Change From Baseline in Gliadin-specific T Cell Cytokine Secretion by ELISA at Day 20 Baseline (Day 15/Day 1): IL-2	1.00 pg/mL Standard Deviation 1.117	1.29 pg/mL Standard Deviation 1.510
Change From Baseline in Gliadin-specific T Cell Cytokine Secretion by ELISA at Day 20 Change at Day 20: IL-2	0.27 pg/mL Standard Deviation 1.180	0.20 pg/mL Standard Deviation 0.932
Change From Baseline in Gliadin-specific T Cell Cytokine Secretion by ELISA at Day 20 Baseline (Day 15/Day 1): IL-4	0.12 pg/mL Standard Deviation 0.180	0.19 pg/mL Standard Deviation 0.388
Change From Baseline in Gliadin-specific T Cell Cytokine Secretion by ELISA at Day 20 Change at Day 20: IL-4	-0.07 pg/mL Standard Deviation 0.227	-0.09 pg/mL Standard Deviation 0.434
Change From Baseline in Gliadin-specific T Cell Cytokine Secretion by ELISA at Day 20 Baseline (Day 15/Day 1): IL-6	-0.59 pg/mL Standard Deviation 18.704	32.06 pg/mL Standard Deviation 123.405
Change From Baseline in Gliadin-specific T Cell Cytokine Secretion by ELISA at Day 20 Change at Day 20: IL-6	12.76 pg/mL Standard Deviation 29.303	-16.88 pg/mL Standard Deviation 131.535
Change From Baseline in Gliadin-specific T Cell Cytokine Secretion by ELISA at Day 20 Baseline (Day 15/Day 1): IL-8	0.03 pg/mL Standard Deviation 0.091	0.00 pg/mL Standard Deviation 0.007
Change From Baseline in Gliadin-specific T Cell Cytokine Secretion by ELISA at Day 20 Change at Day 20: IL-8	-0.03 pg/mL Standard Deviation 0.091	0.00 pg/mL Standard Deviation 0.007
Change From Baseline in Gliadin-specific T Cell Cytokine Secretion by ELISA at Day 20 Baseline (Day 15/Day 1): TNF-α	2.25 pg/mL Standard Deviation 2.763	11.75 pg/mL Standard Deviation 27.434
Change From Baseline in Gliadin-specific T Cell Cytokine Secretion by ELISA at Day 20 Change at Day 20: TNF-α	3.20 pg/mL Standard Deviation 3.099	-1.95 pg/mL Standard Deviation 33.181

SECONDARY outcome

Timeframe: Baseline (Day 15/Day 1), Day 20

Population: The pharmacodynamic population included all randomized participants who received two doses of study medication, completed at least the first 3 days of the gluten challenge (12 g/day for 3 days), and had pharmacodynamic results on Study Days 1, 15, and 20.

Change from baseline value for Gut-Homing cells like CD4, CD8 and Gamma Delta T-cells were reported. Baseline (Day 15/Day 1) was defined as Day 15 (or Day 1 if enough blood was not available on Day 15). Phenotype (unique cell population) for CD8 cell is EM CD8 \> aE+b7hi \> aE+b7hiCD38+, for CD4 is EM Th \> a4+b7hi \> a4+b7hiCD38+ and for Gamma Delta T-cells is TCRgd T cells \> aE+b7hi \> aE+b7hiCD38+ in this outcome measure.

Outcome measures

Outcome measures
Measure	TIMP-GLIA 8 mg/kg n=13 Participants TIMP-GLIA 8 mg/kg, infusion, intravenously, once on Days 1 and 8.	Placebo n=16 Participants TIMP-GLIA placebo-matching infusion, intravenously, once on Days 1 and 8.
Change From Baseline in Gut-Homing CD4, CD8 and Gamma Delta T-cells by Mass Cytometry (CyTOF) at Day 20 Baseline (Day 15/Day 1): CD8	0.21 percent parent Standard Deviation 0.216	0.18 percent parent Standard Deviation 0.285
Change From Baseline in Gut-Homing CD4, CD8 and Gamma Delta T-cells by Mass Cytometry (CyTOF) at Day 20 Change at Day 20: CD8	0.69 percent parent Standard Deviation 0.979	3.64 percent parent Standard Deviation 3.685
Change From Baseline in Gut-Homing CD4, CD8 and Gamma Delta T-cells by Mass Cytometry (CyTOF) at Day 20 Baseline (Day 15/Day 1): CD4	0.19 percent parent Standard Deviation 0.210	0.16 percent parent Standard Deviation 0.189
Change From Baseline in Gut-Homing CD4, CD8 and Gamma Delta T-cells by Mass Cytometry (CyTOF) at Day 20 Change at Day 20: CD4	0.26 percent parent Standard Deviation 0.549	1.05 percent parent Standard Deviation 1.223
Change From Baseline in Gut-Homing CD4, CD8 and Gamma Delta T-cells by Mass Cytometry (CyTOF) at Day 20 Baseline (Day 15/Day 1): Gamma Delta T-cells	0.20 percent parent Standard Deviation 0.186	0.13 percent parent Standard Deviation 0.318
Change From Baseline in Gut-Homing CD4, CD8 and Gamma Delta T-cells by Mass Cytometry (CyTOF) at Day 20 Change at Day 20: Gamma Delta T-cells	0.15 percent parent Standard Deviation 0.378	1.59 percent parent Standard Deviation 2.598

SECONDARY outcome

Timeframe: Baseline (Screening), Day 29

Population: The histology population included all randomized participants who received two doses of study medication, completed the gluten challenge per protocol, and had both a baseline and Day 29 biopsy.

Attenuation of the effects of gluten exposure was assessed by measuring the change from baseline in villous height (Vh) to crypt depth (Cd) ratio after 29 days of gluten challenge. Villi were the small finger like projections that line the small intestine and promote nutrient absorption and are often shortened in participants with CD. Crypts are grooves between the villi that are often elongated in participants with CD. A decreased Vh:Cd ratio indicates worsening disease. Baseline was defined as the last sample collected prior to the first dose of study medication (Screening Period) on Day 1.

Outcome measures

Outcome measures
Measure	TIMP-GLIA 8 mg/kg n=13 Participants TIMP-GLIA 8 mg/kg, infusion, intravenously, once on Days 1 and 8.	Placebo n=15 Participants TIMP-GLIA placebo-matching infusion, intravenously, once on Days 1 and 8.
Change From Baseline in Ratio of Villus Height to Crypt Depth (Vh:Cd) at Day 29 Baseline (Screening): Vh:Cd	2.82 ratio Standard Deviation 0.306	3.01 ratio Standard Deviation 0.451
Change From Baseline in Ratio of Villus Height to Crypt Depth (Vh:Cd) at Day 29 Change at Day 29: Vh:Cd:	-0.18 ratio Standard Deviation 0.381	-0.63 ratio Standard Deviation 0.657

SECONDARY outcome

Timeframe: Day 29

Villi were the small finger like projections that line the small intestine and promote nutrient absorption and are often shortened in participants with CD. Crypts are grooves between the villi that are often elongated in participants with CD. A decreased Vh:Cd ratio indicates worsening disease.

Outcome measures

Outcome measures
Measure	TIMP-GLIA 8 mg/kg n=13 Participants TIMP-GLIA 8 mg/kg, infusion, intravenously, once on Days 1 and 8.	Placebo n=15 Participants TIMP-GLIA placebo-matching infusion, intravenously, once on Days 1 and 8.
Percentage of Participants With Greater Than or Equal to (>=) 0.4 Decrease in Vh:Cd at Day 29	23.1 percentage of participants	53.3 percentage of participants

SECONDARY outcome

Timeframe: Baseline (Screening), Day 29

IELs were white blood cells interspersed between epithelial cells of the small and large intestine where they function to preserve the integrity of the mucosal barrier by protecting the epithelium against pathogen or immune-induced pathology. Increased intraepithelial lymphocytes was associated with celiac disease. Baseline was defined as the last sample collected prior to the first dose of study medication (Screening Period) on Day 1.

Outcome measures

Outcome measures
Measure	TIMP-GLIA 8 mg/kg n=13 Participants TIMP-GLIA 8 mg/kg, infusion, intravenously, once on Days 1 and 8.	Placebo n=15 Participants TIMP-GLIA placebo-matching infusion, intravenously, once on Days 1 and 8.
Change From Baseline in Number of Intestinal Intraepithelial Lymphocytes (IELs) at Day 29 Baseline (Screening): IELs	39.62 cells per 100 enterocytes Standard Deviation 18.842	34.53 cells per 100 enterocytes Standard Deviation 12.389
Change From Baseline in Number of Intestinal Intraepithelial Lymphocytes (IELs) at Day 29 Change at Day 29: IELs	28.62 cells per 100 enterocytes Standard Deviation 19.241	35.00 cells per 100 enterocytes Standard Deviation 18.756

SECONDARY outcome

Timeframe: Days 15, 20, 29 and 35

Population: The safety population included all randomized participants who received at least one dose of study medication. Here, "number analyzed" signifies the participants who were evaluable for this outcome measure for given time points.

The CSI were clinically oriented, easily administered, questionnaires with 16 items. The modified CSI (6-items) was derived from a subset of questions from the CSI questionnaire, including the diarrhea, nausea, rumbling in stomach, stomach felt bloated, diarrhea and low energy level abdominal pain domains (a total of 6 questions), which were each assessed on a scale of 1 to 5- none of the time, a little of the time, some of the time, most of the time and all of the time respectively. Higher CSI scores correlate with more severe CD symptoms. It is to be used to assess symptoms before, during, and after the oral gluten challenge. Here D refers to Day.

Outcome measures

Outcome measures
Measure	TIMP-GLIA 8 mg/kg n=16 Participants TIMP-GLIA 8 mg/kg, infusion, intravenously, once on Days 1 and 8.	Placebo n=18 Participants TIMP-GLIA placebo-matching infusion, intravenously, once on Days 1 and 8.
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 20, Low energy level: Some	0 participants	2 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 29, Pain/discomfort in abdomen/stomach: A little	2 participants	5 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 20, Rumbling in stomach: None	6 participants	6 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 15, Rumbling in stomach: All time	0 participants	0 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 15, Diarrhea: None	14 participants	15 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 15, Diarrhea: Some	0 participants	0 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 15, Low energy level: None	6 participants	11 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 20, Nausea: Some	3 participants	3 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 20, Rumbling in stomach: A little	2 participants	6 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 20, Rumbling in stomach: All time	1 participants	1 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 20, Stomach felt bloated: None	7 participants	4 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 20, Diarrhea: None	8 participants	11 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 20, Low energy level: None	3 participants	6 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 20, Low energy level: A little	5 participants	6 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 29, Pain/discomfort in abdomen/stomach: All time	0 participants	1 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 29, Rumbling in stomach: A little	1 participants	5 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 35, Stomach felt bloated: All time	0 participants	0 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 35, Diarrhea: Most	0 participants	1 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 20, Nausea: Most	1 participants	2 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 20, Nausea: All time	1 participants	1 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 20, Low energy level: Most	4 participants	2 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 20, Low energy level: All time	2 participants	2 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 29, Pain/discomfort in abdomen/stomach: None	6 participants	10 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 29, Pain/discomfort in abdomen/stomach: Some	4 participants	2 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 29, Pain/discomfort in abdomen/stomach: Most	1 participants	0 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 29, Nausea: None	8 participants	9 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 29, Nausea: A little	3 participants	5 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 29, Nausea: Some	1 participants	1 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 29, Nausea: Most	1 participants	2 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 29, Nausea: All time	0 participants	1 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 29, Rumbling in stomach: None	7 participants	9 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 29, Rumbling in stomach: Some	3 participants	2 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 29, Rumbling in stomach: Most	2 participants	1 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 29, Rumbling in stomach: All time	0 participants	1 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 29, Stomach felt bloated: None	7 participants	8 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 29, Stomach felt bloated: A little	1 participants	6 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 29, Stomach felt bloated: Some	2 participants	1 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 29, Stomach felt bloated: Most	2 participants	2 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 29, Stomach felt bloated: All time	1 participants	1 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 29, Diarrhea: None	10 participants	13 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 29, Diarrhea: A little	1 participants	3 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 29, Diarrhea: Some	2 participants	1 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 29, Diarrhea: Most	0 participants	0 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 29, Diarrhea: All time	0 participants	1 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 29, Low energy level: None	4 participants	8 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 29, Low energy level: A little	3 participants	6 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 29, Low energy level: Some	2 participants	3 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 29, Low energy level: Most	3 participants	0 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 29, Low energy level: All time	1 participants	1 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 35, Pain/discomfort in abdomen/stomach: None	8 participants	15 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 35, Pain/discomfort in abdomen/stomach: A little	4 participants	2 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 35, Pain/discomfort in abdomen/stomach: Some	1 participants	1 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 35, Pain/discomfort in abdomen/stomach: Most	0 participants	0 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 35, Pain/discomfort in abdomen/stomach: All time	0 participants	0 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 35, Nausea: None	9 participants	16 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 35, Nausea: A little	2 participants	2 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 35, Nausea: Some	2 participants	0 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 35, Nausea: Most	0 participants	0 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 35, Nausea: All time	0 participants	0 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 35, Rumbling in stomach: None	10 participants	11 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 35, Rumbling in stomach: A little	1 participants	7 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 35, Rumbling in stomach: Some	2 participants	0 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 35, Rumbling in stomach: Most	0 participants	0 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 35, Rumbling in stomach: All time	0 participants	0 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 35, Stomach felt bloated: None	8 participants	10 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 35, Stomach felt bloated: A little	3 participants	6 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 35, Stomach felt bloated: Some	2 participants	2 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 35, Stomach felt bloated: Most	0 participants	0 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 35, Diarrhea: None	11 participants	14 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 35, Diarrhea: A little	2 participants	3 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 35, Diarrhea: Some	0 participants	0 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 35, Diarrhea: All time	0 participants	0 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 35, Low energy level: None	7 participants	14 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 35, Low energy level: A little	1 participants	2 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 35, Low energy level: Some	4 participants	0 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 35, Low energy level: Most	1 participants	2 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 35, Low energy level: All time	0 participants	0 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 20, Pain/discomfort in abdomen/stomach: Most	3 participants	2 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 20, Pain/discomfort in abdomen/stomach: All time	0 participants	1 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 20, Nausea: None	4 participants	5 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 20, Nausea: A little	5 participants	7 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 15, Pain/discomfort in abdomen/stomach: None	11 participants	13 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 15, Pain/discomfort in abdomen/stomach: A little	3 participants	4 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 15, Pain/discomfort in abdomen/stomach: Some	2 participants	1 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 15, Pain/discomfort in abdomen/stomach: Most	0 participants	0 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 15, Pain/discomfort in abdomen/stomach: All time	0 participants	0 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 15, Nausea: None	12 participants	15 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 15, Nausea: A little	2 participants	2 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 15, Nausea: Some	1 participants	1 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 15, Nausea: Most	1 participants	0 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 15, Nausea: All time	0 participants	0 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 15, Rumbling in stomach: None	12 participants	11 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 15, Rumbling in stomach: A little	2 participants	5 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 15, Rumbling in stomach: Some	2 participants	2 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 15, Rumbling in stomach: Most	0 participants	0 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 15, Stomach felt bloated: None	11 participants	10 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 15, Stomach felt bloated: A little	4 participants	7 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 15, Stomach felt bloated: Some	1 participants	0 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 15, Stomach felt bloated: Most	0 participants	1 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 15, Stomach felt bloated: All time	0 participants	0 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 15, Diarrhea: A little	2 participants	3 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 15, Diarrhea: Most	0 participants	0 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 15, Diarrhea: All time	0 participants	0 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 15, Low energy level: A little	5 participants	5 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 15, Low energy level: Some	3 participants	1 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 15, Low energy level: Most	2 participants	1 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 15, Low energy level: All time	0 participants	0 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 20, Pain/discomfort in abdomen/stomach: None	5 participants	8 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 20, Pain/discomfort in abdomen/stomach: A little	4 participants	3 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 20, Pain/discomfort in abdomen/stomach: Some	2 participants	4 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 20, Rumbling in stomach: Some	4 participants	3 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 20, Rumbling in stomach: Most	1 participants	2 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 20, Stomach felt bloated: A little	2 participants	8 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 20, Stomach felt bloated: Some	1 participants	3 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 20, Stomach felt bloated: Most	2 participants	1 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 20, Stomach felt bloated: All time	2 participants	2 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 20, Diarrhea: A little	2 participants	4 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 20, Diarrhea: Some	3 participants	3 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 20, Diarrhea: Most	1 participants	0 participants
Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment D 20, Diarrhea: All time	0 participants	0 participants

SECONDARY outcome

Timeframe: Day 8: 0 hours (pre-infusion), end of infusion, and at 2 hours post-infusion

Population: The pharmacokinetic population included all randomized participants who received two doses of study medication and had at least one reported concentration. The pharmacokinetic population where data at specified time points were available.

Outcome measures

Outcome measures
Measure	TIMP-GLIA 8 mg/kg n=16 Participants TIMP-GLIA 8 mg/kg, infusion, intravenously, once on Days 1 and 8.	Placebo TIMP-GLIA placebo-matching infusion, intravenously, once on Days 1 and 8.
Plasma Concentrations of TIMP-GLIA 0 hours (pre-infusion)	13.06 nanogram per milliliter (ng/mL) Standard Deviation 52.250	—
Plasma Concentrations of TIMP-GLIA End of Infusion	684.54 nanogram per milliliter (ng/mL) Standard Deviation 319.069	—
Plasma Concentrations of TIMP-GLIA 2 hours post infusion	383.46 nanogram per milliliter (ng/mL) Standard Deviation 153.225	—

SECONDARY outcome

Timeframe: From the first dose of study drug up to Day 35

Population: The safety population included all randomized participants who received at least one dose of study medication.

Outcome measures

Outcome measures
Measure	TIMP-GLIA 8 mg/kg n=16 Participants TIMP-GLIA 8 mg/kg, infusion, intravenously, once on Days 1 and 8.	Placebo n=18 Participants TIMP-GLIA placebo-matching infusion, intravenously, once on Days 1 and 8.
Number of Participants Who Experience at Least 1 Treatment-emergent Adverse Event (TEAE) and Serious Adverse Event (SAE) TEAE	16 Participants	18 Participants
Number of Participants Who Experience at Least 1 Treatment-emergent Adverse Event (TEAE) and Serious Adverse Event (SAE) SAE	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From the first dose of study drug up to Day 35

Population: The safety population included all randomized participants who received at least one dose of study medication.

Outcome measures

Outcome measures
Measure	TIMP-GLIA 8 mg/kg n=16 Participants TIMP-GLIA 8 mg/kg, infusion, intravenously, once on Days 1 and 8.	Placebo n=18 Participants TIMP-GLIA placebo-matching infusion, intravenously, once on Days 1 and 8.
Number of Participants With Clinically Significant Change From Baseline in Vital Signs	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From the first dose of study drug up to Day 35

Population: The safety population included all randomized participants who received at least one dose of study medication.

Outcome measures

Outcome measures
Measure	TIMP-GLIA 8 mg/kg n=16 Participants TIMP-GLIA 8 mg/kg, infusion, intravenously, once on Days 1 and 8.	Placebo n=18 Participants TIMP-GLIA placebo-matching infusion, intravenously, once on Days 1 and 8.
Number of Participants With Clinically Significant Change From Baseline in Hematology or Serum Chemistry Laboratory Values	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline (Screening), Days 8, 15, 20, 29, and 35

Population: The safety population included all randomized participants who received at least one dose of study medication. Participants evaluable for this measure at given time point were included for the assessment.

Baseline was defined as the last sample collected prior to the first dose of study medication (Screening Period) on Day 1.

Outcome measures

Outcome measures
Measure	TIMP-GLIA 8 mg/kg n=16 Participants TIMP-GLIA 8 mg/kg, infusion, intravenously, once on Days 1 and 8.	Placebo n=18 Participants TIMP-GLIA placebo-matching infusion, intravenously, once on Days 1 and 8.
Change From Baseline in Deamidated Gliadin Peptide Immunoglobulin G (DGP-IgG) Antibodies at Days 8, 15, 20, 29, and 35 Baseline (Screening)	7.9 units Standard Deviation 11.53	5.9 units Standard Deviation 3.48
Change From Baseline in Deamidated Gliadin Peptide Immunoglobulin G (DGP-IgG) Antibodies at Days 8, 15, 20, 29, and 35 Change at Day 8	4.3 units Standard Deviation 7.43	-0.6 units Standard Deviation 1.58
Change From Baseline in Deamidated Gliadin Peptide Immunoglobulin G (DGP-IgG) Antibodies at Days 8, 15, 20, 29, and 35 Change at Day 15	27.8 units Standard Deviation 28.92	0.3 units Standard Deviation 1.67
Change From Baseline in Deamidated Gliadin Peptide Immunoglobulin G (DGP-IgG) Antibodies at Days 8, 15, 20, 29, and 35 Change at Day 20	28.6 units Standard Deviation 29.63	-0.1 units Standard Deviation 1.76
Change From Baseline in Deamidated Gliadin Peptide Immunoglobulin G (DGP-IgG) Antibodies at Days 8, 15, 20, 29, and 35 Change at Day 29	28.4 units Standard Deviation 31.27	8.9 units Standard Deviation 13.23
Change From Baseline in Deamidated Gliadin Peptide Immunoglobulin G (DGP-IgG) Antibodies at Days 8, 15, 20, 29, and 35 Change at Day 35	28.4 units Standard Deviation 29.68	20.7 units Standard Deviation 27.04

SECONDARY outcome

Timeframe: Baseline (Day 1), Days 2, 8, 9, and 15

Population: The safety population included all randomized participants who received at least one dose of study medication.

Baseline was defined as the pre-dose value on Day 1.

Outcome measures

Outcome measures
Measure	TIMP-GLIA 8 mg/kg n=16 Participants TIMP-GLIA 8 mg/kg, infusion, intravenously, once on Days 1 and 8.	Placebo n=18 Participants TIMP-GLIA placebo-matching infusion, intravenously, once on Days 1 and 8.
Change From Baseline in Serum Complement Levels of C3a and SC5B-9 at Days 2, 8, 9, and 15 Baseline (Day 1): C3a	1024.0 ng/mL Standard Deviation 430.15	1069.9 ng/mL Standard Deviation 435.78
Change From Baseline in Serum Complement Levels of C3a and SC5B-9 at Days 2, 8, 9, and 15 Change at Day 2: C3a	-144.6 ng/mL Standard Deviation 452.51	112.3 ng/mL Standard Deviation 1086.95
Change From Baseline in Serum Complement Levels of C3a and SC5B-9 at Days 2, 8, 9, and 15 Change at Day 8: C3a	244.7 ng/mL Standard Deviation 449.20	-115.3 ng/mL Standard Deviation 385.44
Change From Baseline in Serum Complement Levels of C3a and SC5B-9 at Days 2, 8, 9, and 15 Change at Day 9: C3a	-63.0 ng/mL Standard Deviation 227.28	-71.2 ng/mL Standard Deviation 441.80
Change From Baseline in Serum Complement Levels of C3a and SC5B-9 at Days 2, 8, 9, and 15 Change at Day 15: C3a	-165.2 ng/mL Standard Deviation 308.01	54.8 ng/mL Standard Deviation 603.56
Change From Baseline in Serum Complement Levels of C3a and SC5B-9 at Days 2, 8, 9, and 15 Baseline (Day 1): SC5B-9	130.5 ng/mL Standard Deviation 44.69	114.7 ng/mL Standard Deviation 40.68
Change From Baseline in Serum Complement Levels of C3a and SC5B-9 at Days 2, 8, 9, and 15 Change at Day 2: SC5B-9	-8.7 ng/mL Standard Deviation 25.83	-4.5 ng/mL Standard Deviation 20.18
Change From Baseline in Serum Complement Levels of C3a and SC5B-9 at Days 2, 8, 9, and 15 Change at Day 8: SC5B-9	866.5 ng/mL Standard Deviation 924.08	-4.6 ng/mL Standard Deviation 28.72
Change From Baseline in Serum Complement Levels of C3a and SC5B-9 at Days 2, 8, 9, and 15 Change at Day 9: SC5B-9	40.5 ng/mL Standard Deviation 137.83	-4.8 ng/mL Standard Deviation 37.18
Change From Baseline in Serum Complement Levels of C3a and SC5B-9 at Days 2, 8, 9, and 15 Change at Day 15: SC5B-9	5.5 ng/mL Standard Deviation 57.06	18.4 ng/mL Standard Deviation 53.46

SECONDARY outcome

Timeframe: Baseline (Day 1) , Days 2, 8, 9, and 15

Population: The safety population included all randomized participants who received at least one dose of study medication.

Baseline was defined as the pre-dose value on Day 1.

Outcome measures

Outcome measures
Measure	TIMP-GLIA 8 mg/kg n=16 Participants TIMP-GLIA 8 mg/kg, infusion, intravenously, once on Days 1 and 8.	Placebo n=18 Participants TIMP-GLIA placebo-matching infusion, intravenously, once on Days 1 and 8.
Change From Baseline in Serum Complement Levels of C5a at Days 2, 8, 9, and 15 Baseline (Day 1)	9.290 microgram per liter (mcg/L) Standard Deviation 6.5091	7.267 microgram per liter (mcg/L) Standard Deviation 3.2526
Change From Baseline in Serum Complement Levels of C5a at Days 2, 8, 9, and 15 Change at Day 2	0.763 microgram per liter (mcg/L) Standard Deviation 1.0587	-0.067 microgram per liter (mcg/L) Standard Deviation 0.6776
Change From Baseline in Serum Complement Levels of C5a at Days 2, 8, 9, and 15 Change at Day 8	8.373 microgram per liter (mcg/L) Standard Deviation 8.0077	0.082 microgram per liter (mcg/L) Standard Deviation 0.7604
Change From Baseline in Serum Complement Levels of C5a at Days 2, 8, 9, and 15 Change at Day 9	0.926 microgram per liter (mcg/L) Standard Deviation 1.3873	0.347 microgram per liter (mcg/L) Standard Deviation 1.0356
Change From Baseline in Serum Complement Levels of C5a at Days 2, 8, 9, and 15 Change at Day 15	0.319 microgram per liter (mcg/L) Standard Deviation 1.7868	0.241 microgram per liter (mcg/L) Standard Deviation 0.9151

SECONDARY outcome

Timeframe: Baseline (Day 1), Days 15, 20, 29, and 35

Population: The safety population included all randomized participants who received at least one dose of study medication. Participants who were evaluable for this measure at given time point were included for the assessment.

Baseline was defined as the pre-dose value on Day 1.

Outcome measures

Outcome measures
Measure	TIMP-GLIA 8 mg/kg n=16 Participants TIMP-GLIA 8 mg/kg, infusion, intravenously, once on Days 1 and 8.	Placebo n=18 Participants TIMP-GLIA placebo-matching infusion, intravenously, once on Days 1 and 8.
Change From Baseline in Serum Complement Levels of C1q Binding at Days 15, 20, 29, and 35 Baseline (Day 1)	3.65 units per milliliter (U/mL) Standard Deviation 2.026	4.53 units per milliliter (U/mL) Standard Deviation 1.962
Change From Baseline in Serum Complement Levels of C1q Binding at Days 15, 20, 29, and 35 Change at Day 15	0.64 units per milliliter (U/mL) Standard Deviation 1.249	0.21 units per milliliter (U/mL) Standard Deviation 1.498
Change From Baseline in Serum Complement Levels of C1q Binding at Days 15, 20, 29, and 35 Change at Day 20	0.88 units per milliliter (U/mL) Standard Deviation 1.315	-0.15 units per milliliter (U/mL) Standard Deviation 1.274
Change From Baseline in Serum Complement Levels of C1q Binding at Days 15, 20, 29, and 35 Change at Day 29	0.10 units per milliliter (U/mL) Standard Deviation 1.901	0.18 units per milliliter (U/mL) Standard Deviation 2.073
Change From Baseline in Serum Complement Levels of C1q Binding at Days 15, 20, 29, and 35 Change at Day 35	0.49 units per milliliter (U/mL) Standard Deviation 1.310	0.09 units per milliliter (U/mL) Standard Deviation 2.116

SECONDARY outcome

Timeframe: Baseline (Day 1), Days 2, 8, 9, and 15

Population: The safety population included all randomized participants who received at least one dose of study medication.

Baseline was defined as Day 1 pre-dose. A negative change from baseline value was reported when the observed sample response was less than the observed background response.

Outcome measures

Outcome measures
Measure	TIMP-GLIA 8 mg/kg n=16 Participants TIMP-GLIA 8 mg/kg, infusion, intravenously, once on Days 1 and 8.	Placebo n=18 Participants TIMP-GLIA placebo-matching infusion, intravenously, once on Days 1 and 8.
Change From Baseline in Serum Cytokines (IFN-γ, IL 1-β, IL-2, IL-4, IL-6, IL-8 , IL-10, IL-12p70, and TNF-Alpha) at Days 2, 8, 9, and 15 Baseline (Day 1): IFN-γ	7.375 pg/mL Standard Deviation 9.5787	4.592 pg/mL Standard Deviation 1.9801
Change From Baseline in Serum Cytokines (IFN-γ, IL 1-β, IL-2, IL-4, IL-6, IL-8 , IL-10, IL-12p70, and TNF-Alpha) at Days 2, 8, 9, and 15 Change at Day 2: IFN-γ	9.871 pg/mL Standard Deviation 19.3167	-0.179 pg/mL Standard Deviation 0.8403
Change From Baseline in Serum Cytokines (IFN-γ, IL 1-β, IL-2, IL-4, IL-6, IL-8 , IL-10, IL-12p70, and TNF-Alpha) at Days 2, 8, 9, and 15 Change at Day 8: IFN-γ	-2.374 pg/mL Standard Deviation 10.3311	5.245 pg/mL Standard Deviation 15.7119
Change From Baseline in Serum Cytokines (IFN-γ, IL 1-β, IL-2, IL-4, IL-6, IL-8 , IL-10, IL-12p70, and TNF-Alpha) at Days 2, 8, 9, and 15 Change at Day 9: IFN-γ	1.663 pg/mL Standard Deviation 14.7044	3.709 pg/mL Standard Deviation 12.0744
Change From Baseline in Serum Cytokines (IFN-γ, IL 1-β, IL-2, IL-4, IL-6, IL-8 , IL-10, IL-12p70, and TNF-Alpha) at Days 2, 8, 9, and 15 Change at Day 15: IFN-γ	0.539 pg/mL Standard Deviation 12.8988	0.871 pg/mL Standard Deviation 2.4732
Change From Baseline in Serum Cytokines (IFN-γ, IL 1-β, IL-2, IL-4, IL-6, IL-8 , IL-10, IL-12p70, and TNF-Alpha) at Days 2, 8, 9, and 15 Baseline (Day 1): IL1-β	0.600 pg/mL Standard Deviation 0.0000	0.600 pg/mL Standard Deviation 0.0000
Change From Baseline in Serum Cytokines (IFN-γ, IL 1-β, IL-2, IL-4, IL-6, IL-8 , IL-10, IL-12p70, and TNF-Alpha) at Days 2, 8, 9, and 15 Change at Day 2: IL1-β	0.000 pg/mL Standard Deviation 0.0000	0.0000 pg/mL Standard Deviation 0.0000
Change From Baseline in Serum Cytokines (IFN-γ, IL 1-β, IL-2, IL-4, IL-6, IL-8 , IL-10, IL-12p70, and TNF-Alpha) at Days 2, 8, 9, and 15 Change at Day 8: IL1-β	0.000 pg/mL Standard Deviation 0.000	0.0000 pg/mL Standard Deviation 0.0000
Change From Baseline in Serum Cytokines (IFN-γ, IL 1-β, IL-2, IL-4, IL-6, IL-8 , IL-10, IL-12p70, and TNF-Alpha) at Days 2, 8, 9, and 15 Change at Day 9: IL1-β	0.000 pg/mL Standard Deviation 0.000	0.0000 pg/mL Standard Deviation 0.0000
Change From Baseline in Serum Cytokines (IFN-γ, IL 1-β, IL-2, IL-4, IL-6, IL-8 , IL-10, IL-12p70, and TNF-Alpha) at Days 2, 8, 9, and 15 Change at Day 15: IL1-β	0.000 pg/mL Standard Deviation 0.000	0.0000 pg/mL Standard Deviation 0.0000
Change From Baseline in Serum Cytokines (IFN-γ, IL 1-β, IL-2, IL-4, IL-6, IL-8 , IL-10, IL-12p70, and TNF-Alpha) at Days 2, 8, 9, and 15 Baseline (Day 1): IL-2	0.731 pg/mL Standard Deviation 0.0450	0.824 pg/mL Standard Deviation 0.4431
Change From Baseline in Serum Cytokines (IFN-γ, IL 1-β, IL-2, IL-4, IL-6, IL-8 , IL-10, IL-12p70, and TNF-Alpha) at Days 2, 8, 9, and 15 Change at Day 2: IL-2	0.004 pg/mL Standard Deviation 0.0175	0.001 pg/mL Standard Deviation 0.0047
Change From Baseline in Serum Cytokines (IFN-γ, IL 1-β, IL-2, IL-4, IL-6, IL-8 , IL-10, IL-12p70, and TNF-Alpha) at Days 2, 8, 9, and 15 Change at Day 8: IL-2	0.008 pg/mL Standard Deviation 0.0325	-0.021 pg/mL Standard Deviation 0.0872
Change From Baseline in Serum Cytokines (IFN-γ, IL 1-β, IL-2, IL-4, IL-6, IL-8 , IL-10, IL-12p70, and TNF-Alpha) at Days 2, 8, 9, and 15 Change at Day 9: IL-2	0.006 pg/mL Standard Deviation 0.0250	-0.022 pg/mL Standard Deviation 0.0943
Change From Baseline in Serum Cytokines (IFN-γ, IL 1-β, IL-2, IL-4, IL-6, IL-8 , IL-10, IL-12p70, and TNF-Alpha) at Days 2, 8, 9, and 15 Change at Day 15: IL-2	0.006 pg/mL Standard Deviation 0.0250	-0.023 pg/mL Standard Deviation 0.0990
Change From Baseline in Serum Cytokines (IFN-γ, IL 1-β, IL-2, IL-4, IL-6, IL-8 , IL-10, IL-12p70, and TNF-Alpha) at Days 2, 8, 9, and 15 Baseline (Day 1): IL-4	0.380 pg/mL Standard Deviation 0.0000	0.380 pg/mL Standard Deviation 0.0000
Change From Baseline in Serum Cytokines (IFN-γ, IL 1-β, IL-2, IL-4, IL-6, IL-8 , IL-10, IL-12p70, and TNF-Alpha) at Days 2, 8, 9, and 15 Change at Day 2: IL-4	0.000 pg/mL Standard Deviation 0.000	0.0000 pg/mL Standard Deviation 0.0000
Change From Baseline in Serum Cytokines (IFN-γ, IL 1-β, IL-2, IL-4, IL-6, IL-8 , IL-10, IL-12p70, and TNF-Alpha) at Days 2, 8, 9, and 15 Change at Day 8: IL-4	0.000 pg/mL Standard Deviation 0.000	0.0000 pg/mL Standard Deviation 0.0000
Change From Baseline in Serum Cytokines (IFN-γ, IL 1-β, IL-2, IL-4, IL-6, IL-8 , IL-10, IL-12p70, and TNF-Alpha) at Days 2, 8, 9, and 15 Change at Day 9: IL-4	0.000 pg/mL Standard Deviation 0.000	0.0000 pg/mL Standard Deviation 0.0000
Change From Baseline in Serum Cytokines (IFN-γ, IL 1-β, IL-2, IL-4, IL-6, IL-8 , IL-10, IL-12p70, and TNF-Alpha) at Days 2, 8, 9, and 15 Change at Day 15: IL-4	0.000 pg/mL Standard Deviation 0.000	0.0000 pg/mL Standard Deviation 0.0000
Change From Baseline in Serum Cytokines (IFN-γ, IL 1-β, IL-2, IL-4, IL-6, IL-8 , IL-10, IL-12p70, and TNF-Alpha) at Days 2, 8, 9, and 15 Baseline (Day 1): IL-6	1.067 pg/mL Standard Deviation 0.3473	1.005 pg/mL Standard Deviation 0.1621
Change From Baseline in Serum Cytokines (IFN-γ, IL 1-β, IL-2, IL-4, IL-6, IL-8 , IL-10, IL-12p70, and TNF-Alpha) at Days 2, 8, 9, and 15 Change at Day 2: IL-6	-0.009 pg/mL Standard Deviation 0.0924	0.069 pg/mL Standard Deviation 0.2733
Change From Baseline in Serum Cytokines (IFN-γ, IL 1-β, IL-2, IL-4, IL-6, IL-8 , IL-10, IL-12p70, and TNF-Alpha) at Days 2, 8, 9, and 15 Change at Day 8: IL-6	0.024 pg/mL Standard Deviation 0.3507	0.169 pg/mL Standard Deviation 0.6991
Change From Baseline in Serum Cytokines (IFN-γ, IL 1-β, IL-2, IL-4, IL-6, IL-8 , IL-10, IL-12p70, and TNF-Alpha) at Days 2, 8, 9, and 15 Change at Day 9: IL-6	0.159 pg/mL Standard Deviation 0.4817	0.051 pg/mL Standard Deviation 0.2330
Change From Baseline in Serum Cytokines (IFN-γ, IL 1-β, IL-2, IL-4, IL-6, IL-8 , IL-10, IL-12p70, and TNF-Alpha) at Days 2, 8, 9, and 15 Change at Day 15: IL-6	-0.059 pg/mL Standard Deviation 0.3768	-0.008 pg/mL Standard Deviation 0.1400
Change From Baseline in Serum Cytokines (IFN-γ, IL 1-β, IL-2, IL-4, IL-6, IL-8 , IL-10, IL-12p70, and TNF-Alpha) at Days 2, 8, 9, and 15 Baseline (Day 1): IL-8	12.602 pg/mL Standard Deviation 5.7067	11.497 pg/mL Standard Deviation 3.9699
Change From Baseline in Serum Cytokines (IFN-γ, IL 1-β, IL-2, IL-4, IL-6, IL-8 , IL-10, IL-12p70, and TNF-Alpha) at Days 2, 8, 9, and 15 Change at Day 2: IL-8	11.159 pg/mL Standard Deviation 17.5276	0.236 pg/mL Standard Deviation 5.6791
Change From Baseline in Serum Cytokines (IFN-γ, IL 1-β, IL-2, IL-4, IL-6, IL-8 , IL-10, IL-12p70, and TNF-Alpha) at Days 2, 8, 9, and 15 Change at Day 8: IL-8	-0.470 pg/mL Standard Deviation 3.1986	-2.177 pg/mL Standard Deviation 3.1075
Change From Baseline in Serum Cytokines (IFN-γ, IL 1-β, IL-2, IL-4, IL-6, IL-8 , IL-10, IL-12p70, and TNF-Alpha) at Days 2, 8, 9, and 15 Change at Day 9: IL-8	5.816 pg/mL Standard Deviation 9.5328	-1.685 pg/mL Standard Deviation 4.1328
Change From Baseline in Serum Cytokines (IFN-γ, IL 1-β, IL-2, IL-4, IL-6, IL-8 , IL-10, IL-12p70, and TNF-Alpha) at Days 2, 8, 9, and 15 Change at Day 15: IL-8	-1.959 pg/mL Standard Deviation 5.0839	-1.394 pg/mL Standard Deviation 4.0435
Change From Baseline in Serum Cytokines (IFN-γ, IL 1-β, IL-2, IL-4, IL-6, IL-8 , IL-10, IL-12p70, and TNF-Alpha) at Days 2, 8, 9, and 15 Baseline (Day 1): IL-10	1.784 pg/mL Standard Deviation 5.4054	0.449 pg/mL Standard Deviation 0.1651
Change From Baseline in Serum Cytokines (IFN-γ, IL 1-β, IL-2, IL-4, IL-6, IL-8 , IL-10, IL-12p70, and TNF-Alpha) at Days 2, 8, 9, and 15 Change at Day 2: IL-10	0.081 pg/mL Standard Deviation 0.0969	0.042 pg/mL Standard Deviation 0.1403
Change From Baseline in Serum Cytokines (IFN-γ, IL 1-β, IL-2, IL-4, IL-6, IL-8 , IL-10, IL-12p70, and TNF-Alpha) at Days 2, 8, 9, and 15 Change at Day 8: IL-10	-0.040 pg/mL Standard Deviation 0.2209	0.017 pg/mL Standard Deviation 0.1701
Change From Baseline in Serum Cytokines (IFN-γ, IL 1-β, IL-2, IL-4, IL-6, IL-8 , IL-10, IL-12p70, and TNF-Alpha) at Days 2, 8, 9, and 15 Change at Day 9: IL-10	0.494 pg/mL Standard Deviation 1.2476	0.067 pg/mL Standard Deviation 0.1695
Change From Baseline in Serum Cytokines (IFN-γ, IL 1-β, IL-2, IL-4, IL-6, IL-8 , IL-10, IL-12p70, and TNF-Alpha) at Days 2, 8, 9, and 15 Change at Day 15: IL-10	0.307 pg/mL Standard Deviation 1.0885	-0.013 pg/mL Standard Deviation 0.0531
Change From Baseline in Serum Cytokines (IFN-γ, IL 1-β, IL-2, IL-4, IL-6, IL-8 , IL-10, IL-12p70, and TNF-Alpha) at Days 2, 8, 9, and 15 Baseline (Day 1): IL-12p70	3.280 pg/mL Standard Deviation 0.0000	3.280 pg/mL Standard Deviation 0.0000
Change From Baseline in Serum Cytokines (IFN-γ, IL 1-β, IL-2, IL-4, IL-6, IL-8 , IL-10, IL-12p70, and TNF-Alpha) at Days 2, 8, 9, and 15 Change at Day 2: IL-12p70	0.0000 pg/mL Standard Deviation 0.0000	0.0000 pg/mL Standard Deviation 0.0000
Change From Baseline in Serum Cytokines (IFN-γ, IL 1-β, IL-2, IL-4, IL-6, IL-8 , IL-10, IL-12p70, and TNF-Alpha) at Days 2, 8, 9, and 15 Change at Day 8: IL-12p70	0.0000 pg/mL Standard Deviation 0.0000	0.0000 pg/mL Standard Deviation 0.0000
Change From Baseline in Serum Cytokines (IFN-γ, IL 1-β, IL-2, IL-4, IL-6, IL-8 , IL-10, IL-12p70, and TNF-Alpha) at Days 2, 8, 9, and 15 Change at Day 9: IL-12p70	0.0000 pg/mL Standard Deviation 0.0000	0.0000 pg/mL Standard Deviation 0.0000
Change From Baseline in Serum Cytokines (IFN-γ, IL 1-β, IL-2, IL-4, IL-6, IL-8 , IL-10, IL-12p70, and TNF-Alpha) at Days 2, 8, 9, and 15 Change at Day 15: IL-12p70	0.0000 pg/mL Standard Deviation 0.0000	0.0000 pg/mL Standard Deviation 0.0000
Change From Baseline in Serum Cytokines (IFN-γ, IL 1-β, IL-2, IL-4, IL-6, IL-8 , IL-10, IL-12p70, and TNF-Alpha) at Days 2, 8, 9, and 15 Baseline (Day 1): TNF-α	2.856 pg/mL Standard Deviation 0.6101	2.421 pg/mL Standard Deviation 0.6177
Change From Baseline in Serum Cytokines (IFN-γ, IL 1-β, IL-2, IL-4, IL-6, IL-8 , IL-10, IL-12p70, and TNF-Alpha) at Days 2, 8, 9, and 15 Change at Day 2: TNF-α	1.218 pg/mL Standard Deviation 1.1446	-0.037 pg/mL Standard Deviation 0.4394
Change From Baseline in Serum Cytokines (IFN-γ, IL 1-β, IL-2, IL-4, IL-6, IL-8 , IL-10, IL-12p70, and TNF-Alpha) at Days 2, 8, 9, and 15 Change at Day 8: TNF-α	0.132 pg/mL Standard Deviation 0.5762	0.080 pg/mL Standard Deviation 0.3451
Change From Baseline in Serum Cytokines (IFN-γ, IL 1-β, IL-2, IL-4, IL-6, IL-8 , IL-10, IL-12p70, and TNF-Alpha) at Days 2, 8, 9, and 15 Change at Day 9: TNF-α	0.801 pg/mL Standard Deviation 0.7369	-0.043 pg/mL Standard Deviation 0.3940
Change From Baseline in Serum Cytokines (IFN-γ, IL 1-β, IL-2, IL-4, IL-6, IL-8 , IL-10, IL-12p70, and TNF-Alpha) at Days 2, 8, 9, and 15 Change at Day 15: TNF-α	0.138 pg/mL Standard Deviation 0.7129	0.083 pg/mL Standard Deviation 0.2492

Adverse Events

TIMP-GLIA 8 mg/kg

Serious events: 0 serious events

Other events: 16 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 18 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Medical Director

Takeda

Phone: +1-877-825-3327

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
Publication restrictions are in place

Restriction type: OTHER