Trial Outcomes & Findings for A Multicenter Trial to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of HZN-825 in Patients With Diffuse Cutaneous Systemic Sclerosis (NCT NCT04781543)

Last Updated: 2026-03-20

Results Overview

FVC was assessed using a blowing device provided by the Sponsor. The best of 3 efforts was defined as the highest FVC, obtained on any of the 3 blows meeting the American Thoracic Society (ATS) and the European Respiratory Society (ERS) criteria with a maximum of 8 maneuvers. FVC% predicted was calculated by taking the observed FVC measurement and dividing it by a predicted value multiplied by 100 (% FVC predicted = (FVC observed/FVC predicted) x 100). The predicted value is an average of the normal FVC volume for a person of the same sex, ethnicity, age and height.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

301 participants

Primary outcome timeframe

Baseline and Week 52

Results posted on

2026-03-20

Participant Flow

A total of 301 participants were enrolled from November 2021 to February 2025 at 137 trial sites across Argentina, Austria, Chile, France, Germany, Greece, Israel, Italy, Japan, Korea, Mexico, Poland, Portugal, Romania, Serbia, Spain, Switzerland, the United Kingdom and the United States.

This trial planned to evaluate the efficacy, safety, tolerability and pharmacokinetics (PK) of fipaxalparant (HZN-825) administed once a day (QD) or twice a day (BID) compared to placebo over a 52-week period in participants with diffuse cutaneous systemic sclerosis (SSc). A futility analysis was conducted after 50% of the participants completed the Week 52 visit and a decision was made to terminate the trial early.

Participant milestones

Participant milestones
Measure	Fipaxalparant 300 mg QD Participants took two fipaxalparant 150 mg tablets in the morning and two placebo tablets in the evening for 52 weeks.	Fipaxalparant 300 mg BID Participants took two fipaxalparant 150 mg tablets in the morning and two fipaxalparant 150 mg tablets in the evening for 52 weeks.	Placebo Participants took two placebo tablets in the morning and two placebo tablets in the evening for 52 weeks.
Overall Study STARTED	100	101	100
Overall Study Intent to Treat (ITT) Analysis Set	100	101	100
Overall Study Safety Analysis Set	100	102	99
Overall Study PK Analysis Set	100	102	99
Overall Study COMPLETED	65	56	64
Overall Study NOT COMPLETED	35	45	36

Reasons for withdrawal

Reasons for withdrawal
Measure	Fipaxalparant 300 mg QD Participants took two fipaxalparant 150 mg tablets in the morning and two placebo tablets in the evening for 52 weeks.	Fipaxalparant 300 mg BID Participants took two fipaxalparant 150 mg tablets in the morning and two fipaxalparant 150 mg tablets in the evening for 52 weeks.	Placebo Participants took two placebo tablets in the morning and two placebo tablets in the evening for 52 weeks.
Overall Study Study Terminated by Sponsor	28	29	29
Overall Study Withdrawal by Subject	7	14	5
Overall Study Lost to Follow-up	0	1	1
Overall Study Death	0	1	1

Baseline Characteristics

A Multicenter Trial to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of HZN-825 in Patients With Diffuse Cutaneous Systemic Sclerosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Fipaxalparant 300 mg QD n=100 Participants Participants took two fipaxalparant 150 mg tablets in the morning and two placebo tablets in the evening for 52 weeks.	Fipaxalparant 300 mg BID n=101 Participants Participants took two fipaxalparant 150 mg tablets in the morning and two fipaxalparant 150 mg tablets in the evening for 52 weeks.	Placebo n=100 Participants Participants took two placebo tablets in the morning and two placebo tablets in the evening for 52 weeks.	Total n=301 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=154 Participants	0 Participants n=151 Participants	0 Participants n=305 Participants	0 Participants n=104 Participants
Age, Categorical Between 18 and 65 years	86 Participants n=154 Participants	87 Participants n=151 Participants	90 Participants n=305 Participants	263 Participants n=104 Participants
Age, Categorical >=65 years	14 Participants n=154 Participants	14 Participants n=151 Participants	10 Participants n=305 Participants	38 Participants n=104 Participants
Sex: Female, Male Female	76 Participants n=154 Participants	78 Participants n=151 Participants	80 Participants n=305 Participants	234 Participants n=104 Participants
Sex: Female, Male Male	24 Participants n=154 Participants	23 Participants n=151 Participants	20 Participants n=305 Participants	67 Participants n=104 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	40 Participants n=154 Participants	33 Participants n=151 Participants	42 Participants n=305 Participants	115 Participants n=104 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	60 Participants n=154 Participants	68 Participants n=151 Participants	58 Participants n=305 Participants	186 Participants n=104 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=154 Participants	0 Participants n=151 Participants	0 Participants n=305 Participants	0 Participants n=104 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=154 Participants	1 Participants n=151 Participants	2 Participants n=305 Participants	3 Participants n=104 Participants
Race/Ethnicity, Customized Asian	9 Participants n=154 Participants	11 Participants n=151 Participants	14 Participants n=305 Participants	34 Participants n=104 Participants
Race/Ethnicity, Customized Black or African American	4 Participants n=154 Participants	2 Participants n=151 Participants	3 Participants n=305 Participants	9 Participants n=104 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=154 Participants	2 Participants n=151 Participants	1 Participants n=305 Participants	3 Participants n=104 Participants
Race/Ethnicity, Customized White	85 Participants n=154 Participants	76 Participants n=151 Participants	77 Participants n=305 Participants	238 Participants n=104 Participants
Race/Ethnicity, Customized Other	2 Participants n=154 Participants	8 Participants n=151 Participants	2 Participants n=305 Participants	12 Participants n=104 Participants
Race/Ethnicity, Customized Unknown or not reported	0 Participants n=154 Participants	1 Participants n=151 Participants	1 Participants n=305 Participants	2 Participants n=104 Participants

PRIMARY outcome

Timeframe: Baseline and Week 52

Population: ITT Analysis Set: participants who were randomized to a treatment regardless of whether they received trial drug or not. Participants with available data at Week 52 were included in the analysis.

Outcome measures

Outcome measures
Measure	Fipaxalparant 300 mg QD n=60 Participants Participants took two fipaxalparant 150 mg tablets in the morning and two placebo tablets in the evening for 52 weeks.	Fipaxalparant 300 mg BID n=55 Participants Participants took two fipaxalparant 150 mg tablets in the morning and two fipaxalparant 150 mg tablets in the evening for 52 weeks.	Placebo n=57 Participants Participants took two placebo tablets in the morning and two placebo tablets in the evening for 52 weeks.
Change From Baseline in Forced Vital Capacity Percent (FVC%) Predicted at Week 52	-2.35 % predicted FVC Standard Error 0.94	-3.22 % predicted FVC Standard Error 0.98	-2.35 % predicted FVC Standard Error 0.94

SECONDARY outcome

Timeframe: Baseline and Week 52

The mRSS is a validated method for estimating skin thickening. Seventeen different body areas were scored as normal (0), mild thickening (1), moderate thickening (2) and severe thickening (3), with a total score range from 0 (best) to 51 (worst). A higher score meant greater disease severity.

Outcome measures

Outcome measures
Measure	Fipaxalparant 300 mg QD n=62 Participants Participants took two fipaxalparant 150 mg tablets in the morning and two placebo tablets in the evening for 52 weeks.	Fipaxalparant 300 mg BID n=54 Participants Participants took two fipaxalparant 150 mg tablets in the morning and two fipaxalparant 150 mg tablets in the evening for 52 weeks.	Placebo n=63 Participants Participants took two placebo tablets in the morning and two placebo tablets in the evening for 52 weeks.
Change From Baseline in the Modified Rodnan Skin Score (mRSS) at Week 52	-9.3 Score on a scale Standard Error 0.9	-10.7 Score on a scale Standard Error 0.9	-8.8 Score on a scale Standard Error 0.9

SECONDARY outcome

Timeframe: Baseline to Week 52

According to the Revised CRISS (CRISS 25), participants were considered responders if there was improvement in at least 2 components: ≥5% increase for FVC% predicted and/or ≥25% decrease for mRSS, the Health Assessment Questionnaire - Disability Index (HAQ-DI), the Patient Global Assessment (PTGA), the Clinician Global Assessment (CGA) and worsening in no more than one component: ≥5% decrease FVC% predicted and/or ≥25% increase for mRSS, HAQ-DI, PTGA, CGA, at 52 weeks.

Outcome measures

Outcome measures
Measure	Fipaxalparant 300 mg QD n=65 Participants Participants took two fipaxalparant 150 mg tablets in the morning and two placebo tablets in the evening for 52 weeks.	Fipaxalparant 300 mg BID n=59 Participants Participants took two fipaxalparant 150 mg tablets in the morning and two fipaxalparant 150 mg tablets in the evening for 52 weeks.	Placebo n=65 Participants Participants took two placebo tablets in the morning and two placebo tablets in the evening for 52 weeks.
Number of Participants Responding to Treatment Based on the Revised Composite Response Index in Systemic Sclerosis (CRISS 25) at Week 52	32 Participants	27 Participants	33 Participants

SECONDARY outcome

Timeframe: Baseline and Week 52

The HAQ-DI assesses the participant's level of functional ability and includes questions of fine movements of the upper extremity, locomotor activities of the lower extremity and activities that involve both upper and lower extremities. There are 20 questions in 8 categories of functioning including dressing, rising, eating, walking, hygiene, reach, grip and usual activities. The HAQ-DI was calculated by scoring the answer to each question in the HAQ from 0 to 3, with 0 representing the ability to do without any difficulty, and 3 representing inability to do. The total HAQ-DI score was obtained by summing the 8 categories scores and dividing by 8. The total HAQ-DI score ranged from 0 to 3. A negative change meant a worsening of functional ability.

Outcome measures

Outcome measures
Measure	Fipaxalparant 300 mg QD n=63 Participants Participants took two fipaxalparant 150 mg tablets in the morning and two placebo tablets in the evening for 52 weeks.	Fipaxalparant 300 mg BID n=57 Participants Participants took two fipaxalparant 150 mg tablets in the morning and two fipaxalparant 150 mg tablets in the evening for 52 weeks.	Placebo n=62 Participants Participants took two placebo tablets in the morning and two placebo tablets in the evening for 52 weeks.
Change From Baseline in HAQ-DI at Week 52	-0.19 Score on a scale Standard Error 0.063	-0.17 Score on a scale Standard Error 0.065	-0.24 Score on a scale Standard Error 0.063

SECONDARY outcome

Timeframe: Baseline and Week 52

The CGA is an 11-point scale ranging from 0 to 10 (0=excellent to 10=extremely poor) on which the physician rated the participant's overall health over the past week. 0 meant an excellent overall health and 10 an extremely poor overall health. A negative change meant an improvement of participant's overall health.

Outcome measures

Outcome measures
Measure	Fipaxalparant 300 mg QD n=58 Participants Participants took two fipaxalparant 150 mg tablets in the morning and two placebo tablets in the evening for 52 weeks.	Fipaxalparant 300 mg BID n=53 Participants Participants took two fipaxalparant 150 mg tablets in the morning and two fipaxalparant 150 mg tablets in the evening for 52 weeks.	Placebo n=58 Participants Participants took two placebo tablets in the morning and two placebo tablets in the evening for 52 weeks.
Change From Baseline in CGA at Week 52	-1.8 Score on a scale Standard Error 0.25	-2.3 Score on a scale Standard Error 0.26	-1.8 Score on a scale Standard Error 0.25

SECONDARY outcome

Timeframe: Baseline and Week 52

The PTGA is an 11-point scale ranging from 0 to 10 (0=excellent to 10=extremely poor) on which the participant rated his/her overall health and illness-related pain level over the past week and how much the skin involvement due to scleroderma had interfered with daily activity and how rapidly the skin disease had been progressing over the past month. A negative change meant an improvement of participant's overall health.

Outcome measures

Outcome measures
Measure	Fipaxalparant 300 mg QD n=63 Participants Participants took two fipaxalparant 150 mg tablets in the morning and two placebo tablets in the evening for 52 weeks.	Fipaxalparant 300 mg BID n=57 Participants Participants took two fipaxalparant 150 mg tablets in the morning and two fipaxalparant 150 mg tablets in the evening for 52 weeks.	Placebo n=62 Participants Participants took two placebo tablets in the morning and two placebo tablets in the evening for 52 weeks.
Change From Baseline in PTGA at Week 52	-0.6 Score on a scale Standard Error 0.27	-0.4 Score on a scale Standard Error 0.29	-1.2 Score on a scale Standard Error 0.28

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: ITT Analysis Set: participants who were randomized to a treatment regardless of whether they received study trial or not. Participants with available data at Week 52 were included in the analysis.

The SSPRO-18 is an 18-item, patient-reported outcome instrument that specifically assesses skin-related quality of life in patients with SSc. The SSPRO-18 comprises 4 major conceptual constructs-physical effects, emotional effects, physical limitations and social effects. The SSPRO-18 Physical Effects Subscale is a composite score transformed to a 0 - 100 scale of several questions relating to the extent to which specific skin-related symptoms were experienced by the subject. Recall is the past 4 weeks. Higher scores indicate more severe impact of skin problems on the participnt's quality of life. A negative change meant an improvement of the skin-related quality of life.

Outcome measures

Outcome measures
Measure	Fipaxalparant 300 mg QD n=63 Participants Participants took two fipaxalparant 150 mg tablets in the morning and two placebo tablets in the evening for 52 weeks.	Fipaxalparant 300 mg BID n=57 Participants Participants took two fipaxalparant 150 mg tablets in the morning and two fipaxalparant 150 mg tablets in the evening for 52 weeks.	Placebo n=62 Participants Participants took two placebo tablets in the morning and two placebo tablets in the evening for 52 weeks.
Change From Baseline in the Physical Effects Subscale of the Scleroderma Skin Patient-reported Outcome (SSPRO-18) at Week 52	-13.35 Score on a scale Standard Error 2.544	-16.12 Score on a scale Standard Error 2.621	-14.0 Score on a scale Standard Error 2.551

SECONDARY outcome

Timeframe: Baseline and Week 52

The SSPRO-18 is an 18-item, patient-reported outcome instrument that specifically assesses skin-related quality of life in patients with SSc. The SSPRO-18 comprises 4 major conceptual constructs-physical effects, emotional effects, physical limitations and social effects. The SSPRO-18 Physical Limitations Subscale is a composite score transformed to a 0 - 100 scale of several questions relating to the extent to which the condition of the subject's skin and skin tightness limited them physically. Recall is the past 4 weeks. Higher scores indicate more severe impact of skin problems on the participant's quality of life. A negative change meant an improvement of the skin-related quality of life.

Outcome measures

Outcome measures
Measure	Fipaxalparant 300 mg QD n=63 Participants Participants took two fipaxalparant 150 mg tablets in the morning and two placebo tablets in the evening for 52 weeks.	Fipaxalparant 300 mg BID n=57 Participants Participants took two fipaxalparant 150 mg tablets in the morning and two fipaxalparant 150 mg tablets in the evening for 52 weeks.	Placebo n=62 Participants Participants took two placebo tablets in the morning and two placebo tablets in the evening for 52 weeks.
Change From Baseline in the Physical Limitations Subscale of the SSPRO-18 at Week 52	-16.67 Score on a scale Standard Error 2.633	-20.15 Score on a scale Standard Error 2.713	-17.94 Score on a scale Standard Error 2.639

SECONDARY outcome

Timeframe: Baseline and Week 52

Outcome measures

Outcome measures
Measure	Fipaxalparant 300 mg QD n=62 Participants Participants took two fipaxalparant 150 mg tablets in the morning and two placebo tablets in the evening for 52 weeks.	Fipaxalparant 300 mg BID n=55 Participants Participants took two fipaxalparant 150 mg tablets in the morning and two fipaxalparant 150 mg tablets in the evening for 52 weeks.	Placebo n=63 Participants Participants took two placebo tablets in the morning and two placebo tablets in the evening for 52 weeks.
Number of Participants With an mRSS Decrease of ≥ 5 Points and 25% From Baseline at Week 52	43 Participants	37 Participants	41 Participants

SECONDARY outcome

Timeframe: Week 52

The American College of Rheumatology (ACR)-CRISS is a 2-step process that assigns a probability of improvement for a participants that ranges from 0.0 (no improvement) to 1.0 (marked improvement). Participants were considered responders if thier ACR-CRISS was at least 0.6.

Outcome measures

Outcome measures
Measure	Fipaxalparant 300 mg QD n=65 Participants Participants took two fipaxalparant 150 mg tablets in the morning and two placebo tablets in the evening for 52 weeks.	Fipaxalparant 300 mg BID n=59 Participants Participants took two fipaxalparant 150 mg tablets in the morning and two fipaxalparant 150 mg tablets in the evening for 52 weeks.	Placebo n=65 Participants Participants took two placebo tablets in the morning and two placebo tablets in the evening for 52 weeks.
Number of Participants Who Were Responders at Week 52	41 Participants	33 Participants	33 Participants

SECONDARY outcome

Timeframe: From first dose to last dose + 28 days, median (min, max) duration was 12.8 (1.0, 13.9) months

Population: Safety Analysis Set: all the participants who received at least 1 dose or partial dose of trial drug. Treatment group assignment was based on the treatment actually received.

A TEAE was any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which dose not necessarily have a causal relationship with this treatment. Changes in vital signs, 12-lead electrocardiograms (ECGs) and clinical safety laboratory evaluations were considered TEAEs. An AESI is an AE (serious or non-serious) of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and rapid communication by the Investigator to the Sponsor may be appropriate. Orthostatic hypotension was considered an AESI.

Outcome measures

Outcome measures
Measure	Fipaxalparant 300 mg QD n=100 Participants Participants took two fipaxalparant 150 mg tablets in the morning and two placebo tablets in the evening for 52 weeks.	Fipaxalparant 300 mg BID n=102 Participants Participants took two fipaxalparant 150 mg tablets in the morning and two fipaxalparant 150 mg tablets in the evening for 52 weeks.	Placebo n=99 Participants Participants took two placebo tablets in the morning and two placebo tablets in the evening for 52 weeks.
Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) and AEs of Special Interest (AESIs) TEAEs	87 Participants	84 Participants	79 Participants
Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) and AEs of Special Interest (AESIs) AESI	3 Participants	0 Participants	2 Participants

SECONDARY outcome

Timeframe: From first dose to last dose + 28 days, median (min, max) duration was 12.8 (1.0, 13.9) months

Population: Safety Analysis Set: all the participants who received at least 1 dose or partial dose of trial drug. Treatment group assignment was based on the treatment actually received.

Concomitant medications were defined as any medication that was ongoing, had a start date on or after the first dose of trial drug, or a stop date on or after the first dose date.

Outcome measures

Outcome measures
Measure	Fipaxalparant 300 mg QD n=100 Participants Participants took two fipaxalparant 150 mg tablets in the morning and two placebo tablets in the evening for 52 weeks.	Fipaxalparant 300 mg BID n=102 Participants Participants took two fipaxalparant 150 mg tablets in the morning and two fipaxalparant 150 mg tablets in the evening for 52 weeks.	Placebo n=99 Participants Participants took two placebo tablets in the morning and two placebo tablets in the evening for 52 weeks.
Number of Participants Who Received Concomitant Medication	100 Participants	102 Participants	97 Participants

SECONDARY outcome

Timeframe: Day 1 (post-dose), Week 4 (pre-dose), Week 10 (anytime at the visit), Weeks 16 and 28 (pre-dose and post-dose) and Weeks 40 and 52 (pre-dose)

Population: PK Analysis Set: all participants who received at least 1 dose or partial dose of fipaxalparant and had at least 1 PK sample post fipaxalparant treatment. Treatment group assignment was based on the treatment actually received.

Plasma concentrations of fipaxalparant were summarized descriptively by treatment group and time point.

Outcome measures

Outcome measures
Measure	Fipaxalparant 300 mg QD n=100 Participants Participants took two fipaxalparant 150 mg tablets in the morning and two placebo tablets in the evening for 52 weeks.	Fipaxalparant 300 mg BID n=102 Participants Participants took two fipaxalparant 150 mg tablets in the morning and two fipaxalparant 150 mg tablets in the evening for 52 weeks.	Placebo Participants took two placebo tablets in the morning and two placebo tablets in the evening for 52 weeks.
Pre- and Post-dose Plasma Concentrations of Fipaxalparant Week 52 (pre-dose)	3420 ng/mL Standard Deviation 4660	11700 ng/mL Standard Deviation 10800	—
Pre- and Post-dose Plasma Concentrations of Fipaxalparant Day 1 (post-dose)	14800 ng/mL Standard Deviation 10100	17100 ng/mL Standard Deviation 15200	—
Pre- and Post-dose Plasma Concentrations of Fipaxalparant Week 4 (pre-dose)	5840 ng/mL Standard Deviation 7030	15600 ng/mL Standard Deviation 11200	—
Pre- and Post-dose Plasma Concentrations of Fipaxalparant Week 10 (pre or post-dose)	5690 ng/mL Standard Deviation 7640	16300 ng/mL Standard Deviation 11600	—
Pre- and Post-dose Plasma Concentrations of Fipaxalparant Week 16 (pre-dose)	4540 ng/mL Standard Deviation 5760	13300 ng/mL Standard Deviation 8660	—
Pre- and Post-dose Plasma Concentrations of Fipaxalparant Week 16 (post-dose)	16500 ng/mL Standard Deviation 9660	22100 ng/mL Standard Deviation 13100	—
Pre- and Post-dose Plasma Concentrations of Fipaxalparant Week 28 (pre-dose)	3890 ng/mL Standard Deviation 4220	13600 ng/mL Standard Deviation 10800	—
Pre- and Post-dose Plasma Concentrations of Fipaxalparant Week 28 (post-dose)	17000 ng/mL Standard Deviation 11500	22800 ng/mL Standard Deviation 13900	—
Pre- and Post-dose Plasma Concentrations of Fipaxalparant Week 40 (pre-dose)	4960 ng/mL Standard Deviation 6310	14400 ng/mL Standard Deviation 11900	—

Adverse Events

Fipaxalparant 300 mg QD

Serious events: 9 serious events

Other events: 58 other events

Deaths: 0 deaths

Fipaxalparant 300 mg BID

Serious events: 8 serious events

Other events: 47 other events

Deaths: 1 deaths

Placebo

Serious events: 5 serious events

Other events: 53 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Fipaxalparant 300 mg QD n=100 participants at risk Participants took two fipaxalparant 150 mg tablets in the morning and two placebo tablets in the evening for 52 weeks.	Fipaxalparant 300 mg BID n=102 participants at risk Participants took two fipaxalparant 150 mg tablets in the morning and two fipaxalparant 150 mg tablets in the evening for 52 weeks.	Placebo n=99 participants at risk Participants took two placebo tablets in the morning and two placebo tablets in the evening for 52 weeks.
Gastrointestinal disorders Diarrhoea	7.0% 7/100 • Death: From randomization to end of trial (EOT), median (min, max) was 12.0 (1.5, 14.4) months. TEAE: From first dose to last dose + 28 days, median (min, max) duration was 12.8 (1.0, 13.9) months. All-cause mortality is reported for all participants enrolled/randomized in the trial. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. Treatment group assignment was based on the treatment actually received.	2.9% 3/102 • Death: From randomization to end of trial (EOT), median (min, max) was 12.0 (1.5, 14.4) months. TEAE: From first dose to last dose + 28 days, median (min, max) duration was 12.8 (1.0, 13.9) months. All-cause mortality is reported for all participants enrolled/randomized in the trial. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. Treatment group assignment was based on the treatment actually received.	13.1% 13/99 • Death: From randomization to end of trial (EOT), median (min, max) was 12.0 (1.5, 14.4) months. TEAE: From first dose to last dose + 28 days, median (min, max) duration was 12.8 (1.0, 13.9) months. All-cause mortality is reported for all participants enrolled/randomized in the trial. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. Treatment group assignment was based on the treatment actually received.
Gastrointestinal disorders Gastrooesophageal reflux disease	3.0% 3/100 • Death: From randomization to end of trial (EOT), median (min, max) was 12.0 (1.5, 14.4) months. TEAE: From first dose to last dose + 28 days, median (min, max) duration was 12.8 (1.0, 13.9) months. All-cause mortality is reported for all participants enrolled/randomized in the trial. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. Treatment group assignment was based on the treatment actually received.	5.9% 6/102 • Death: From randomization to end of trial (EOT), median (min, max) was 12.0 (1.5, 14.4) months. TEAE: From first dose to last dose + 28 days, median (min, max) duration was 12.8 (1.0, 13.9) months. All-cause mortality is reported for all participants enrolled/randomized in the trial. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. Treatment group assignment was based on the treatment actually received.	5.1% 5/99 • Death: From randomization to end of trial (EOT), median (min, max) was 12.0 (1.5, 14.4) months. TEAE: From first dose to last dose + 28 days, median (min, max) duration was 12.8 (1.0, 13.9) months. All-cause mortality is reported for all participants enrolled/randomized in the trial. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. Treatment group assignment was based on the treatment actually received.
Gastrointestinal disorders Vomiting	3.0% 3/100 • Death: From randomization to end of trial (EOT), median (min, max) was 12.0 (1.5, 14.4) months. TEAE: From first dose to last dose + 28 days, median (min, max) duration was 12.8 (1.0, 13.9) months. All-cause mortality is reported for all participants enrolled/randomized in the trial. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. Treatment group assignment was based on the treatment actually received.	2.0% 2/102 • Death: From randomization to end of trial (EOT), median (min, max) was 12.0 (1.5, 14.4) months. TEAE: From first dose to last dose + 28 days, median (min, max) duration was 12.8 (1.0, 13.9) months. All-cause mortality is reported for all participants enrolled/randomized in the trial. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. Treatment group assignment was based on the treatment actually received.	6.1% 6/99 • Death: From randomization to end of trial (EOT), median (min, max) was 12.0 (1.5, 14.4) months. TEAE: From first dose to last dose + 28 days, median (min, max) duration was 12.8 (1.0, 13.9) months. All-cause mortality is reported for all participants enrolled/randomized in the trial. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. Treatment group assignment was based on the treatment actually received.
General disorders Oedema peripheral	6.0% 6/100 • Death: From randomization to end of trial (EOT), median (min, max) was 12.0 (1.5, 14.4) months. TEAE: From first dose to last dose + 28 days, median (min, max) duration was 12.8 (1.0, 13.9) months. All-cause mortality is reported for all participants enrolled/randomized in the trial. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. Treatment group assignment was based on the treatment actually received.	0.98% 1/102 • Death: From randomization to end of trial (EOT), median (min, max) was 12.0 (1.5, 14.4) months. TEAE: From first dose to last dose + 28 days, median (min, max) duration was 12.8 (1.0, 13.9) months. All-cause mortality is reported for all participants enrolled/randomized in the trial. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. Treatment group assignment was based on the treatment actually received.	0.00% 0/99 • Death: From randomization to end of trial (EOT), median (min, max) was 12.0 (1.5, 14.4) months. TEAE: From first dose to last dose + 28 days, median (min, max) duration was 12.8 (1.0, 13.9) months. All-cause mortality is reported for all participants enrolled/randomized in the trial. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. Treatment group assignment was based on the treatment actually received.
Infections and infestations COVID-19	10.0% 10/100 • Death: From randomization to end of trial (EOT), median (min, max) was 12.0 (1.5, 14.4) months. TEAE: From first dose to last dose + 28 days, median (min, max) duration was 12.8 (1.0, 13.9) months. All-cause mortality is reported for all participants enrolled/randomized in the trial. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. Treatment group assignment was based on the treatment actually received.	5.9% 6/102 • Death: From randomization to end of trial (EOT), median (min, max) was 12.0 (1.5, 14.4) months. TEAE: From first dose to last dose + 28 days, median (min, max) duration was 12.8 (1.0, 13.9) months. All-cause mortality is reported for all participants enrolled/randomized in the trial. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. Treatment group assignment was based on the treatment actually received.	9.1% 9/99 • Death: From randomization to end of trial (EOT), median (min, max) was 12.0 (1.5, 14.4) months. TEAE: From first dose to last dose + 28 days, median (min, max) duration was 12.8 (1.0, 13.9) months. All-cause mortality is reported for all participants enrolled/randomized in the trial. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. Treatment group assignment was based on the treatment actually received.
Infections and infestations Gastroenteritis	5.0% 5/100 • Death: From randomization to end of trial (EOT), median (min, max) was 12.0 (1.5, 14.4) months. TEAE: From first dose to last dose + 28 days, median (min, max) duration was 12.8 (1.0, 13.9) months. All-cause mortality is reported for all participants enrolled/randomized in the trial. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. Treatment group assignment was based on the treatment actually received.	4.9% 5/102 • Death: From randomization to end of trial (EOT), median (min, max) was 12.0 (1.5, 14.4) months. TEAE: From first dose to last dose + 28 days, median (min, max) duration was 12.8 (1.0, 13.9) months. All-cause mortality is reported for all participants enrolled/randomized in the trial. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. Treatment group assignment was based on the treatment actually received.	6.1% 6/99 • Death: From randomization to end of trial (EOT), median (min, max) was 12.0 (1.5, 14.4) months. TEAE: From first dose to last dose + 28 days, median (min, max) duration was 12.8 (1.0, 13.9) months. All-cause mortality is reported for all participants enrolled/randomized in the trial. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. Treatment group assignment was based on the treatment actually received.
Infections and infestations Nasopharyngitis	7.0% 7/100 • Death: From randomization to end of trial (EOT), median (min, max) was 12.0 (1.5, 14.4) months. TEAE: From first dose to last dose + 28 days, median (min, max) duration was 12.8 (1.0, 13.9) months. All-cause mortality is reported for all participants enrolled/randomized in the trial. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. Treatment group assignment was based on the treatment actually received.	5.9% 6/102 • Death: From randomization to end of trial (EOT), median (min, max) was 12.0 (1.5, 14.4) months. TEAE: From first dose to last dose + 28 days, median (min, max) duration was 12.8 (1.0, 13.9) months. All-cause mortality is reported for all participants enrolled/randomized in the trial. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. Treatment group assignment was based on the treatment actually received.	8.1% 8/99 • Death: From randomization to end of trial (EOT), median (min, max) was 12.0 (1.5, 14.4) months. TEAE: From first dose to last dose + 28 days, median (min, max) duration was 12.8 (1.0, 13.9) months. All-cause mortality is reported for all participants enrolled/randomized in the trial. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. Treatment group assignment was based on the treatment actually received.
Infections and infestations Upper respiratory tract infection	6.0% 6/100 • Death: From randomization to end of trial (EOT), median (min, max) was 12.0 (1.5, 14.4) months. TEAE: From first dose to last dose + 28 days, median (min, max) duration was 12.8 (1.0, 13.9) months. All-cause mortality is reported for all participants enrolled/randomized in the trial. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. Treatment group assignment was based on the treatment actually received.	9.8% 10/102 • Death: From randomization to end of trial (EOT), median (min, max) was 12.0 (1.5, 14.4) months. TEAE: From first dose to last dose + 28 days, median (min, max) duration was 12.8 (1.0, 13.9) months. All-cause mortality is reported for all participants enrolled/randomized in the trial. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. Treatment group assignment was based on the treatment actually received.	6.1% 6/99 • Death: From randomization to end of trial (EOT), median (min, max) was 12.0 (1.5, 14.4) months. TEAE: From first dose to last dose + 28 days, median (min, max) duration was 12.8 (1.0, 13.9) months. All-cause mortality is reported for all participants enrolled/randomized in the trial. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. Treatment group assignment was based on the treatment actually received.
Infections and infestations Urinary tract infection	16.0% 16/100 • Death: From randomization to end of trial (EOT), median (min, max) was 12.0 (1.5, 14.4) months. TEAE: From first dose to last dose + 28 days, median (min, max) duration was 12.8 (1.0, 13.9) months. All-cause mortality is reported for all participants enrolled/randomized in the trial. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. Treatment group assignment was based on the treatment actually received.	6.9% 7/102 • Death: From randomization to end of trial (EOT), median (min, max) was 12.0 (1.5, 14.4) months. TEAE: From first dose to last dose + 28 days, median (min, max) duration was 12.8 (1.0, 13.9) months. All-cause mortality is reported for all participants enrolled/randomized in the trial. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. Treatment group assignment was based on the treatment actually received.	7.1% 7/99 • Death: From randomization to end of trial (EOT), median (min, max) was 12.0 (1.5, 14.4) months. TEAE: From first dose to last dose + 28 days, median (min, max) duration was 12.8 (1.0, 13.9) months. All-cause mortality is reported for all participants enrolled/randomized in the trial. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. Treatment group assignment was based on the treatment actually received.
Musculoskeletal and connective tissue disorders Arthralgia	6.0% 6/100 • Death: From randomization to end of trial (EOT), median (min, max) was 12.0 (1.5, 14.4) months. TEAE: From first dose to last dose + 28 days, median (min, max) duration was 12.8 (1.0, 13.9) months. All-cause mortality is reported for all participants enrolled/randomized in the trial. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. Treatment group assignment was based on the treatment actually received.	2.0% 2/102 • Death: From randomization to end of trial (EOT), median (min, max) was 12.0 (1.5, 14.4) months. TEAE: From first dose to last dose + 28 days, median (min, max) duration was 12.8 (1.0, 13.9) months. All-cause mortality is reported for all participants enrolled/randomized in the trial. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. Treatment group assignment was based on the treatment actually received.	11.1% 11/99 • Death: From randomization to end of trial (EOT), median (min, max) was 12.0 (1.5, 14.4) months. TEAE: From first dose to last dose + 28 days, median (min, max) duration was 12.8 (1.0, 13.9) months. All-cause mortality is reported for all participants enrolled/randomized in the trial. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. Treatment group assignment was based on the treatment actually received.
Nervous system disorders Headache	7.0% 7/100 • Death: From randomization to end of trial (EOT), median (min, max) was 12.0 (1.5, 14.4) months. TEAE: From first dose to last dose + 28 days, median (min, max) duration was 12.8 (1.0, 13.9) months. All-cause mortality is reported for all participants enrolled/randomized in the trial. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. Treatment group assignment was based on the treatment actually received.	4.9% 5/102 • Death: From randomization to end of trial (EOT), median (min, max) was 12.0 (1.5, 14.4) months. TEAE: From first dose to last dose + 28 days, median (min, max) duration was 12.8 (1.0, 13.9) months. All-cause mortality is reported for all participants enrolled/randomized in the trial. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. Treatment group assignment was based on the treatment actually received.	4.0% 4/99 • Death: From randomization to end of trial (EOT), median (min, max) was 12.0 (1.5, 14.4) months. TEAE: From first dose to last dose + 28 days, median (min, max) duration was 12.8 (1.0, 13.9) months. All-cause mortality is reported for all participants enrolled/randomized in the trial. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. Treatment group assignment was based on the treatment actually received.
Respiratory, thoracic and mediastinal disorders Cough	1.0% 1/100 • Death: From randomization to end of trial (EOT), median (min, max) was 12.0 (1.5, 14.4) months. TEAE: From first dose to last dose + 28 days, median (min, max) duration was 12.8 (1.0, 13.9) months. All-cause mortality is reported for all participants enrolled/randomized in the trial. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. Treatment group assignment was based on the treatment actually received.	5.9% 6/102 • Death: From randomization to end of trial (EOT), median (min, max) was 12.0 (1.5, 14.4) months. TEAE: From first dose to last dose + 28 days, median (min, max) duration was 12.8 (1.0, 13.9) months. All-cause mortality is reported for all participants enrolled/randomized in the trial. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. Treatment group assignment was based on the treatment actually received.	3.0% 3/99 • Death: From randomization to end of trial (EOT), median (min, max) was 12.0 (1.5, 14.4) months. TEAE: From first dose to last dose + 28 days, median (min, max) duration was 12.8 (1.0, 13.9) months. All-cause mortality is reported for all participants enrolled/randomized in the trial. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. Treatment group assignment was based on the treatment actually received.
Skin and subcutaneous tissue disorders Skin ulcer	6.0% 6/100 • Death: From randomization to end of trial (EOT), median (min, max) was 12.0 (1.5, 14.4) months. TEAE: From first dose to last dose + 28 days, median (min, max) duration was 12.8 (1.0, 13.9) months. All-cause mortality is reported for all participants enrolled/randomized in the trial. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. Treatment group assignment was based on the treatment actually received.	2.0% 2/102 • Death: From randomization to end of trial (EOT), median (min, max) was 12.0 (1.5, 14.4) months. TEAE: From first dose to last dose + 28 days, median (min, max) duration was 12.8 (1.0, 13.9) months. All-cause mortality is reported for all participants enrolled/randomized in the trial. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. Treatment group assignment was based on the treatment actually received.	6.1% 6/99 • Death: From randomization to end of trial (EOT), median (min, max) was 12.0 (1.5, 14.4) months. TEAE: From first dose to last dose + 28 days, median (min, max) duration was 12.8 (1.0, 13.9) months. All-cause mortality is reported for all participants enrolled/randomized in the trial. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. Treatment group assignment was based on the treatment actually received.

Additional Information

Study Director

Amgen Inc.

Phone: 866-572-6436

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
Publication restrictions are in place

Restriction type: OTHER