Trial Outcomes & Findings for A Two-part Proof-of-Concept Study Assessing the Safety and Efficacy of LAT8881 in Lumbar Radicular Pain (NCT NCT05298306)

Last Updated: 2024-11-27

Results Overview

The number of participants in Part A with the following adverse events will be reported by dose (with all placebo subjects combined) * All adverse events * Serious adverse events * Adverse events leading to premature discontinuation of Investigational Medicinal Product (IMP) * Adverse events by intensity * Adverse events by relationship to IMP

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

26 participants

Primary outcome timeframe

From first dose of LAT8881 to end of study visit (Day 14)

Results posted on

2024-11-27

Participant Flow

The study was conducted in two parts. Part A was a single ascending dose study of intravenous LAT8881 in healthy volunteers. The second part of the study (Part B) was initiated after completion of Part A and was a crossover study of LAT8881 in subjects with lumbar radicular pain. Both parts of the study were randomized, placebo-controlled and double-blinded.

Following a pre-planned interim analysis, Part B of the study was closed to enrolment after 17 subjects had completed the study.

Participant milestones

Participant milestones
Measure	Part A (0.8 mg/kg; 1.2 mg/kg; 1.8 mg/kg) Doses were administered as a single intravenous infusion on Days 1, 4 and 7	Part A (0.8 mg/kg; 1.2 mg/kg; Placebo) Doses were administered as a single intravenous infusion on Days 1, 4 and 7	Part A (0.8 mg/kg; Placebo; 1.8 mg/kg) Doses were administered as a single intravenous infusion on Days 1, 4 and 7	Part A (Placebo; 1.2 mg/kg; 1.8 mg/kg) Doses were administered as a single intravenous infusion on Days 1, 4 and 7	Part B, LAT8881/Placebo LAT8881 was given as a single intravenous infusion on Day 1 at a dose of 1.8 mg/kg. Placebo was administered as a single intravenous infusion on the following day	Part B Placebo/LAT8881 Placebo was administered as a single intravenous infusion on Day 1. LAT8881 was given as a single intravenous infusion on the following day at a dose of 1.8 mg/kg
Overall Study STARTED	2	2	2	3	8	9
Overall Study COMPLETED	2	2	2	2	8	9
Overall Study NOT COMPLETED	0	0	0	1	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Part A (0.8 mg/kg; 1.2 mg/kg; 1.8 mg/kg) Doses were administered as a single intravenous infusion on Days 1, 4 and 7	Part A (0.8 mg/kg; 1.2 mg/kg; Placebo) Doses were administered as a single intravenous infusion on Days 1, 4 and 7	Part A (0.8 mg/kg; Placebo; 1.8 mg/kg) Doses were administered as a single intravenous infusion on Days 1, 4 and 7	Part A (Placebo; 1.2 mg/kg; 1.8 mg/kg) Doses were administered as a single intravenous infusion on Days 1, 4 and 7	Part B, LAT8881/Placebo LAT8881 was given as a single intravenous infusion on Day 1 at a dose of 1.8 mg/kg. Placebo was administered as a single intravenous infusion on the following day	Part B Placebo/LAT8881 Placebo was administered as a single intravenous infusion on Day 1. LAT8881 was given as a single intravenous infusion on the following day at a dose of 1.8 mg/kg
Overall Study Physician Decision	0	0	0	1	0	0

Baseline Characteristics

A Two-part Proof-of-Concept Study Assessing the Safety and Efficacy of LAT8881 in Lumbar Radicular Pain

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part A (0.8 mg/kg; 1.2 mg/kg; 1.8 mg/kg) n=2 Participants Doses were administered as a single intravenous infusion on Days 1, 4 and 7	Part A (0.8 mg/kg; 1.2 mg/kg; Placebo) n=2 Participants Doses were administered as a single intravenous infusion on Days 1, 4 and 7	Part A (0.8 mg/kg; Placebo; 1.8 mg/kg) n=2 Participants Doses were administered as a single intravenous infusion on Days 1, 4 and 7	Part A (Placebo; 1.2 mg/kg; 1.8 mg/kg) n=3 Participants Doses were administered as a single intravenous infusion on Days 1, 4 and 7	Part B, LAT8881/Placebo n=8 Participants LAT8881 was given as a single intravenous infusion on Day 1 at a dose of 1.8 mg/kg. Placebo was administered as a single intravenous infusion on the following day	Part B Placebo/LAT8881 n=9 Participants Placebo was administered as a single intravenous infusion on Day 1. LAT8881 was given as a single intravenous infusion on the following day at a dose of 1.8 mg/kg	Total n=26 Participants Total of all reporting groups
Age, Continuous	26.0 years STANDARD_DEVIATION 4.2 • n=99 Participants	28.5 years STANDARD_DEVIATION 3.5 • n=107 Participants	21.0 years STANDARD_DEVIATION 1.4 • n=206 Participants	26.0 years STANDARD_DEVIATION 4.0 • n=7 Participants	51.9 years STANDARD_DEVIATION 13.5 • n=31 Participants	56.0 years STANDARD_DEVIATION 11.9 • n=30 Participants	44.2 years STANDARD_DEVIATION 17.2 • n=3 Participants
Sex: Female, Male Female	2 Participants n=99 Participants	2 Participants n=107 Participants	1 Participants n=206 Participants	1 Participants n=7 Participants	3 Participants n=31 Participants	6 Participants n=30 Participants	15 Participants n=3 Participants
Sex: Female, Male Male	0 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants	2 Participants n=7 Participants	5 Participants n=31 Participants	3 Participants n=30 Participants	11 Participants n=3 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	1 Participants n=31 Participants	0 Participants n=30 Participants	1 Participants n=3 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	2 Participants n=99 Participants	2 Participants n=107 Participants	2 Participants n=206 Participants	3 Participants n=7 Participants	7 Participants n=31 Participants	9 Participants n=30 Participants	25 Participants n=3 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants	0 Participants n=30 Participants	0 Participants n=3 Participants
Region of Enrollment Australia	2 participants n=99 Participants	2 participants n=107 Participants	2 participants n=206 Participants	3 participants n=7 Participants	8 participants n=31 Participants	9 participants n=30 Participants	26 participants n=3 Participants

PRIMARY outcome

Timeframe: From first dose of LAT8881 to end of study visit (Day 14)

Population: Safety population. This population included all subjects who received at least one dose of IMP and had at least one post dose safety assessment.

Outcome measures

Outcome measures
Measure	Part A, LAT8881 0.8 mg/kg n=6 Participants LAT8881 was given as a single intravenous infusion at a dose of 0.8 mg/kg	Part A, LAT8881 1.2 mg/kg n=6 Participants LAT8881 was given as a single intravenous infusion at a dose of 1.2 mg/kg	Part A, LAT8881 1.8 mg/kg n=6 Participants LAT8881 was given as a single intravenous infusion at a dose of 1.8 mg/kg	Part A, Placebo n=6 Participants Placebo was given as a single intravenous infusion
The Number of Participants With Adverse Events by Dose (Part A) Adverse events related to IMP (possibly, probably or definitely)	0 participants	0 participants	2 participants	1 participants
The Number of Participants With Adverse Events by Dose (Part A) Any adverse event	1 participants	1 participants	2 participants	2 participants
The Number of Participants With Adverse Events by Dose (Part A) Serious adverse event	0 participants	0 participants	0 participants	0 participants
The Number of Participants With Adverse Events by Dose (Part A) Adverse events leading to premature discontinuation of Investigational Medicinal Product (IMP)	0 participants	0 participants	0 participants	0 participants
The Number of Participants With Adverse Events by Dose (Part A) Adverse event of Grade 3 or 4 severity	0 participants	0 participants	0 participants	0 participants

PRIMARY outcome

Timeframe: From start of infusion to 6 hours after start of infusion

Population: Full Analysis Set. This population included all enrolled and randomised participants.

Change in pain from baseline is measured on on a 0-10 Visual Analogue Scale (VAS). The VAS consists of a 10 cm line with two endpoints representing 0 (no pain) and 10 (pain as bad as it could possibly be). The subject is asked to rate their current level of pain by placing a mark on the line and the distance from 0 is measured to provide a pain intensity score out of 10. VAS measurements are taken as the infusion starts and at 15 minute intervals for the first hour, then every thirty minutes for an additional two hours, then hourly until 6 hours from infusion commencement

Outcome measures

Outcome measures
Measure	Part A, LAT8881 0.8 mg/kg n=17 Participants LAT8881 was given as a single intravenous infusion at a dose of 0.8 mg/kg	Part A, LAT8881 1.2 mg/kg n=17 Participants LAT8881 was given as a single intravenous infusion at a dose of 1.2 mg/kg	Part A, LAT8881 1.8 mg/kg LAT8881 was given as a single intravenous infusion at a dose of 1.8 mg/kg	Part A, Placebo Placebo was given as a single intravenous infusion
Change in Baseline Pain With Intravenous LAT8881 in Patients With Lumbar Radicular Pain (Part B) Pre-dose VAS score	3.7 score on a scale Standard Deviation 2.7	3.1 score on a scale Standard Deviation 2.3	—	—
Change in Baseline Pain With Intravenous LAT8881 in Patients With Lumbar Radicular Pain (Part B) Change from pre-dose score at 0.25 hours	-0.8 score on a scale Standard Deviation 1.8	-0.3 score on a scale Standard Deviation 1.1	—	—
Change in Baseline Pain With Intravenous LAT8881 in Patients With Lumbar Radicular Pain (Part B) Change from pre-dose score at 0.5 hours	-0.8 score on a scale Standard Deviation 2.0	-0.3 score on a scale Standard Deviation 1.5	—	—
Change in Baseline Pain With Intravenous LAT8881 in Patients With Lumbar Radicular Pain (Part B) Change from pre-dose score at 0.75 hours	-1.0 score on a scale Standard Deviation 1.8	-0.5 score on a scale Standard Deviation 1.5	—	—
Change in Baseline Pain With Intravenous LAT8881 in Patients With Lumbar Radicular Pain (Part B) Change from pre-dose score at 1.0 hours	-1.1 score on a scale Standard Deviation 2.2	-0.6 score on a scale Standard Deviation 1.4	—	—
Change in Baseline Pain With Intravenous LAT8881 in Patients With Lumbar Radicular Pain (Part B) Change from pre-dose score at 1.5 hours	-0.8 score on a scale Standard Deviation 1.8	-0.5 score on a scale Standard Deviation 1.1	—	—
Change in Baseline Pain With Intravenous LAT8881 in Patients With Lumbar Radicular Pain (Part B) Change from pre-dose score at 2 hours	-0.8 score on a scale Standard Deviation 2.0	-0.4 score on a scale Standard Deviation 1.4	—	—
Change in Baseline Pain With Intravenous LAT8881 in Patients With Lumbar Radicular Pain (Part B) Change from pre-dose score at 2.5 hours	-0.8 score on a scale Standard Deviation 2.1	-0.6 score on a scale Standard Deviation 1.4	—	—
Change in Baseline Pain With Intravenous LAT8881 in Patients With Lumbar Radicular Pain (Part B) Change from pre-dose score at 3 hours	-0.6 score on a scale Standard Deviation 1.9	-0.7 score on a scale Standard Deviation 1.5	—	—
Change in Baseline Pain With Intravenous LAT8881 in Patients With Lumbar Radicular Pain (Part B) Change from pre-dose score at 3.5 hours	-0.8 score on a scale Standard Deviation 2.1	-0.8 score on a scale Standard Deviation 1.4	—	—
Change in Baseline Pain With Intravenous LAT8881 in Patients With Lumbar Radicular Pain (Part B) Change from pre-dose score at 4 hours	-0.9 score on a scale Standard Deviation 2.0	-0.5 score on a scale Standard Deviation 1.5	—	—
Change in Baseline Pain With Intravenous LAT8881 in Patients With Lumbar Radicular Pain (Part B) Change from pre-dose score at 5 hours	-1.0 score on a scale Standard Deviation 2.2	-0.7 score on a scale Standard Deviation 1.6	—	—
Change in Baseline Pain With Intravenous LAT8881 in Patients With Lumbar Radicular Pain (Part B) Change from pre-dose score at 6 hours	-1.2 score on a scale Standard Deviation 2.0	-0.8 score on a scale Standard Deviation 1.4	—	—

SECONDARY outcome

Timeframe: Up to 6 hours after the start of each infusion

Population: Subgroup of the pharmacokinetic population. Data for subjects with no measurable levels of LAT8881 were excluded from the summary.

LAT8881 is measured in plasma samples taken pre-dose and at 5 minutes, 0.25, 0.5, 1, 2, 4 and 6 hours after IMP administration

Outcome measures

Outcome measures
Measure	Part A, LAT8881 0.8 mg/kg n=3 Participants LAT8881 was given as a single intravenous infusion at a dose of 0.8 mg/kg	Part A, LAT8881 1.2 mg/kg n=5 Participants LAT8881 was given as a single intravenous infusion at a dose of 1.2 mg/kg	Part A, LAT8881 1.8 mg/kg n=5 Participants LAT8881 was given as a single intravenous infusion at a dose of 1.8 mg/kg	Part A, Placebo Placebo was given as a single intravenous infusion
Maximum Plasma LAT8881 Concentration (Cmax) After Intravenous LAT8881 (Part A)	12.6 ng/mL Standard Deviation 19.1	10.2 ng/mL Standard Deviation 12.9	13.8 ng/mL Standard Deviation 14.1	—

SECONDARY outcome

Timeframe: Up to 6 hours after the start of each infusion

Population: Subgroup of the pharmacokinetic population. Data for a subject with no measurable levels of LAT8881 were excluded from the summary.

LAT8881 was measured in plasma samples taken pre-dose and at 5 minutes, 0.25, 0.5, 1, 2, 4 and 6 hours after IMP administration

Outcome measures

Outcome measures
Measure	Part A, LAT8881 0.8 mg/kg n=3 Participants LAT8881 was given as a single intravenous infusion at a dose of 0.8 mg/kg	Part A, LAT8881 1.2 mg/kg n=5 Participants LAT8881 was given as a single intravenous infusion at a dose of 1.2 mg/kg	Part A, LAT8881 1.8 mg/kg n=5 Participants LAT8881 was given as a single intravenous infusion at a dose of 1.8 mg/kg	Part A, Placebo Placebo was given as a single intravenous infusion
Time to Maximum Plasma LAT8881 Concentration (Tmax) After Intravenous LAT8881 (Part A)	0.08 hours Standard Deviation 0	0.08 hours Standard Deviation 0	0.08 hours Standard Deviation 0	—

SECONDARY outcome

Timeframe: Up to 6 hours after the start of each infusion

Population: Subgroup of the pharmacokinetic population. Data for subjects with no measurable levels of LAT8881 were excluded from the summary. (AUC0-inf) was not calculated as the criteria of at least three quantifiable data points was not met

LAT8881 was measured in plasma samples taken pre-dose and at 5 minutes, 0.25, 0.5, 1, 2, 4 and 6 hours after IMP administration. (AUC0-inf) was calculated only if there were at least three quantifiable data points.

Outcome measures

Outcome measures
Measure	Part A, LAT8881 0.8 mg/kg n=3 Participants LAT8881 was given as a single intravenous infusion at a dose of 0.8 mg/kg	Part A, LAT8881 1.2 mg/kg n=5 Participants LAT8881 was given as a single intravenous infusion at a dose of 1.2 mg/kg	Part A, LAT8881 1.8 mg/kg n=5 Participants LAT8881 was given as a single intravenous infusion at a dose of 1.8 mg/kg	Part A, Placebo Placebo was given as a single intravenous infusion
Area Under the Concentration Time Curve From Zero to Infinity (AUC0-inf) After Intravenous LAT8881 (Part A)	NA ng/mL*h Standard Deviation NA (AUC0-inf) was not calculated as the criteria of at least three quantifiable data points was not met	NA ng/mL*h Standard Deviation NA (AUC0-inf) was not calculated as the criteria of at least three quantifiable data points was not met	NA ng/mL*h Standard Deviation NA (AUC0-inf) was not calculated as the criteria of at least three quantifiable data points was not met	—

SECONDARY outcome

Timeframe: Up to 6 hours after the start of each infusion

Population: Subgroup of the pharmacokinetic population. Data for a subject with no measurable levels of LAT8881 were excluded from the summary. Terminal half-life could not be determined as the criteria of at least three quantifiable elimination phase data points was not met

LAT8881 was measured in plasma samples taken pre-dose and at 5 minutes, 0.25, 0.5, 1, 2, 4 and 6 hours after IMP administration. The terminal elimination half life was only determined if there were at least three quantifiable elimination phase data points.

Outcome measures

Outcome measures
Measure	Part A, LAT8881 0.8 mg/kg n=3 Participants LAT8881 was given as a single intravenous infusion at a dose of 0.8 mg/kg	Part A, LAT8881 1.2 mg/kg n=5 Participants LAT8881 was given as a single intravenous infusion at a dose of 1.2 mg/kg	Part A, LAT8881 1.8 mg/kg n=5 Participants LAT8881 was given as a single intravenous infusion at a dose of 1.8 mg/kg	Part A, Placebo Placebo was given as a single intravenous infusion
Terminal Elimination Half Life (T1/2), (Part A)	NA hours Standard Deviation NA Terminal half-life could not be determined as the criteria of at least three quantifiable elimination phase data points was not met	NA hours Standard Deviation NA Terminal half-life could not be determined as the criteria of at least three quantifiable elimination phase data points was not met	NA hours Standard Deviation NA Terminal half-life could not be determined as the criteria of at least three quantifiable elimination phase data points was not met	—

SECONDARY outcome

Timeframe: 6 hours after the start of each infusion

Population: PGIC was measured in the Full Analysis Set. This population consisted of all subjects who were enrolled and randomised into the study

The Patient General Impression of Change (PGIC) is a single-item rating by subjects of their improvement with treatment during a clinical trial. Participants were asked to select one of the following options after each treatment: very much improved, much improved, slightly improved, no change, slightly worse, much worse, very much worse.

Outcome measures

Outcome measures
Measure	Part A, LAT8881 0.8 mg/kg n=17 Participants LAT8881 was given as a single intravenous infusion at a dose of 0.8 mg/kg	Part A, LAT8881 1.2 mg/kg n=17 Participants LAT8881 was given as a single intravenous infusion at a dose of 1.2 mg/kg	Part A, LAT8881 1.8 mg/kg LAT8881 was given as a single intravenous infusion at a dose of 1.8 mg/kg	Part A, Placebo Placebo was given as a single intravenous infusion
Patient General Impression of Change (Part B) Slightly worse	1 Participants	0 Participants	—	—
Patient General Impression of Change (Part B) Much worse	0 Participants	0 Participants	—	—
Patient General Impression of Change (Part B) Very much improved	2 Participants	0 Participants	—	—
Patient General Impression of Change (Part B) Much improved	3 Participants	2 Participants	—	—
Patient General Impression of Change (Part B) Slightly improved	4 Participants	11 Participants	—	—
Patient General Impression of Change (Part B) No change	7 Participants	4 Participants	—	—
Patient General Impression of Change (Part B) Very much worse	0 Participants	0 Participants	—	—

SECONDARY outcome

Timeframe: From start of infusion to end of study visit (Day 9)

Population: The safety population consisted of all randomized participants who received at least one dose of IMP and had at least one post dose safety assessment.

The number of participants in Part B with the following adverse events will be reported after placebo and after intravenous LAT8881 * All adverse events * Serious adverse events * Adverse events leading to premature discontinuation of Investigational Medicinal Product (IMP) * Adverse events by intensity * Adverse events by relationship to IMP

Outcome measures

Outcome measures
Measure	Part A, LAT8881 0.8 mg/kg n=17 Participants LAT8881 was given as a single intravenous infusion at a dose of 0.8 mg/kg	Part A, LAT8881 1.2 mg/kg n=17 Participants LAT8881 was given as a single intravenous infusion at a dose of 1.2 mg/kg	Part A, LAT8881 1.8 mg/kg LAT8881 was given as a single intravenous infusion at a dose of 1.8 mg/kg	Part A, Placebo Placebo was given as a single intravenous infusion
The Number of Participants With Adverse Events After Intravenous LAT8881 in Patients With Lumbar Radicular Pain (Part B) Serious adverse event	0 participants	0 participants	—	—
The Number of Participants With Adverse Events After Intravenous LAT8881 in Patients With Lumbar Radicular Pain (Part B) Any adverse event	5 participants	4 participants	—	—
The Number of Participants With Adverse Events After Intravenous LAT8881 in Patients With Lumbar Radicular Pain (Part B) Adverse event leading to discontinuation	0 participants	0 participants	—	—
The Number of Participants With Adverse Events After Intravenous LAT8881 in Patients With Lumbar Radicular Pain (Part B) Adverse event of Grade 3 or 4 severity	0 participants	0 participants	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: From start of infusion to 6 hours after start of infusion

Population: Full analysis set. This population included all subjects who were enrolled and randomised into the study.

Change in pain from baseline is measured on a 0-10 Visual Analogue Scale (VAS). The VAS consists of a 10 cm line with two endpoints representing 0 (no pain) and 10 (pain as bad as it could possibly be). The subject is asked to rate their current level of pain on leg raising by placing a mark on the line and the distance from 0 is measured to provide a pain intensity score out of 10. VAS measurements are taken as the infusion starts and at 15 minute intervals for the first hour, then every thirty minutes for an additional two hours, then hourly until 6 hours from infusion commencement. Each measurement ranges from 0 to 10. The difference from the pre-dose score is calculated at specified timepoints up to 6 hours post-dose.