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TerminatedNCT04781543Updated Mar 20, 2026Results posted

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

A Phase 2 interventional study of HZN-825 BID and Placebo in Diffuse Cutaneous Systemic Sclerosis and Sclerosis, Systemic, sponsored by Amgen. Terminated at 4 sites in 2 countries. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2026-03-20.

Sponsored by Amgen · Phase 2, Interventional, and Treatment

Why this study was terminated
The study was terminated due to meeting pre-defined criteria for futility.
Phase
Phase 2
Study type
Interventional
Enrollment
301
Allocation
Randomized
Ages
18 Years to 75 Years
Sex
All
01

Study summary

This is a randomized, double-blind, placebo-controlled, repeat-dose, multicenter trial. Participants will be screened within 6 weeks prior to the Baseline (Day 1) Visit. Approximately 300 participants who meet the trial eligibility criteria will be randomized on Day 1 in a 1:1:1 ratio to receive HZN-825 300 mg QD, HZN-825 300 mg BID or placebo for 52 weeks.

The trial will include up to a 42-day Screening Period and a 52-week Double-blind Treatment Period. Participants will take their first dose of trial drug at the clinic and will participate in trial visits at Week 4 and every 6 weeks thereafter until Week 52.

All participants who complete the Double-blind Treatment Period (Week 52) will be eligible to enter a 52-week extension trial (HZNP-HZN-825-302, NCT05626751). Participants not entering the extension trial will participate in a Safety Follow-up Visit 4 weeks after the last dose of trial drug.

Read the detailed description

Acquired from Horizon in 2024.

02

Conditions studied

  • Diffuse Cutaneous Systemic Sclerosis
  • Sclerosis, Systemic

Keywords

  • Scleroderma
03

In context

Scleroderma, Diffuse

528 studies on the registry are indexed under Scleroderma, Diffuse; 114 are open to participants now.

This study's enrollment of 301 is above the median of 33 across 366 interventional studies indexed under Scleroderma, Diffuse.

Browse Scleroderma, Diffuse studies →

Lead sponsor

Amgen is the lead sponsor of 1,015 studies on the registry; 49 are open to participants now.

Of its 245 completed or terminated interventional studies of FDA-regulated products, 159 (65%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 75 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Written informed consent.
  2. Male or female between the ages of 18 and 75 years, inclusive, at Screening.
  3. Meets the 2013 American College of Rheumatology/European League Against Rheumatism classification criteria for SSc with a total score of ≥9 (Van den Hoogen et al., 2013).
  4. Classified as having skin involvement proximal to the elbow and knee (diffuse cutaneous SSc subset by LeRoy and Medsger, 2001).
  5. At the time of enrollment, less than or equal to 72 months (6 years) since the onset of the first SSc manifestation, other than Raynaud's phenomenon.
  6. Skin thickening from SSc in the forearm suitable for repeat biopsy.
  7. mRSS units ≥15 at Screening.
  8. FVC ≥45% predicted at Screening, as determined by spirometry.
  9. Willing and able to comply with the prescribed treatment protocol and evaluations for the duration of the trial.

Exclusion criteria

Exclusion Criteria:

  1. Positive for anti-centromere antibodies with the exception that subjects who are positive for both anti-centromere and anti-topoisomerase 1 antibodies may be enrolled.
  2. Diagnosed with sine scleroderma or limited cutaneous SSc.
  3. Diagnosed with other autoimmune connective tissue diseases, except for fibromyalgia, scleroderma-associated myopathy and secondary Sjogren's syndrome.
  4. Scleroderma renal crisis diagnosed within 6 months of the Screening Visit.

  5. Any of the following cardiovascular diseases:

    1. uncontrolled, severe hypertension (≥160/100 mmHg) or persistent low blood pressure (systolic blood pressure \<90 mmHg) within 6 months of Screening,
    2. myocardial infarction within 6 months of Screening,
    3. unstable cardiac angina within 6 months of Screening.
  6. DLCO \<40% predicted (corrected for hemoglobin). If severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure is of clinical concern for any subject, consider using a DLCO up to 6 months before the Screening Visit.
  7. Pulmonary arterial hypertension (PAH) by right heart catheterization requiring treatment with more than 1 oral PAH-approved therapy or any parenteral therapy. Treatment is allowed for erectile dysfunction and/or Raynaud's phenomenon/digital ulcers.
  8. Corticosteroid use for conditions other than SSc within 4 weeks prior to Screening (topical steroids for dermatological conditions and inhaled/intranasal/intra-articular steroids are allowed).
  9. Use of any other non-steroid immunosuppressive agent, small biologic molecule, cytotoxic or anti-fibrotic drug within 4 weeks of Screening, including cyclophosphamide, azathioprine (Imuran®) or other immunosuppressive or cytotoxic medication. Exceptions include mycophenolate mofetil (CellCept®), mycophenolic acid (Myfortic®), methotrexate and low-dose prednisone, as follows: use of CellCept ≤3 g/day, Myfortic ≤2.14 g/day, methotrexate ≤20 mg/week and prednisone ≤10 mg/day (or equivalent dosing of glucocorticoids) is allowed. Subjects taking CellCept, Myfortic or methotrexate must have been doing so for ≥6 months and the dose must have been stable for ≥4 weeks prior to the Day 1 Visit. Prednisone must have been at a stable dose for ≥8 weeks prior to the Day 1 Visit. It is acceptable to be on background low-dose prednisone and anti-malarial drug along with CellCept, Myfortic or methotrexate. Rituximab must not have been used within 6 months of the Day 1 Visit.
  10. Known active bacterial, viral, fungal, mycobacterial or other infection, including tuberculosis or atypical mycobacterial disease (fungal infections of nail beds are allowed) at the time of randomization.
  11. Use of a United States Food and Drug Administration-approved agent for SSc or an investigational agent for any condition within 90 days or 5 half-lives, whichever is longer, prior to Screening or anticipated use during the course of the trial.
  12. Malignant condition in the past 5 years (except successfully treated basal/squamous cell carcinoma of the skin or cervical cancer in situ).
  13. Women of childbearing potential or male subjects not agreeing to use highly effective method(s) of birth control throughout the trial and for 1 month after last dose of trial drug. Male subjects must refrain from sperm donation and females from egg/ova donation for this same time period.
  14. Pregnant or lactating women.
  15. Current drug or alcohol abuse or history of either within the previous 2 years, in the opinion of the Investigator or as reported by the subject.
  16. Previous enrollment in this trial or participation in a prior HZN-825 or SAR100842 clinical trial.
  17. Known history of positive test for human immunodeficiency virus (HIV). HIV testing is optional based on Investigator assessment, institutional practices or local guidelines to rule out suspected HIV or potential for a positive HIV result. Subject consent is required prior to HIV testing.
  18. Active hepatitis (hepatitis B: positive hepatitis B surface antigen and positive anti-hepatitis B core antibody [anti-HBcAb] and negative hepatitis B surface antibody [HBsAb] or positive for HBcAb with a positive test for HBsAb and with presence of hepatitis B virus DNA at Screening; hepatitis C: positive anti-hepatitis C virus [anti-HCV] and positive RNA HCV).
  19. Current alcoholic liver disease, primary biliary cirrhosis or primary sclerosing cholangitis.
  20. Previous organ transplant (including allogeneic and autologous marrow transplant).
  21. International normalized ratio >2, prolonged prothrombin time >1.5 × the upper limit of normal (ULN) or partial thromboplastin time >1.5 × ULN at Screening.
  22. Alanine aminotransferase or aspartate aminotransferase >2 × ULN.
  23. Estimated glomerular filtration rate \<30 mL/min/1.73 m\^2 at Screening.
  24. Total bilirubin >2 × ULN. Subjects with documented diagnosis of Gilbert's syndrome may be enrolled if their total bilirubin is ≤3.0 mg/dL.
  25. Any other condition that, in the opinion of the Investigator, would preclude enrollment in the trial.
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Care provider, Investigator)
Enrollment
301 participants (actual)

Study arms

  • Experimental
    HZN-825 300 mg once daily (QD)

    One set of 2 HZN-825 150mg tablets in the morning and one set of 2 placebo tablets in the evening.

    Drug: HZN-825 QD

  • Experimental
    HZN-825 300 mg twice daily (BID)

    One set of 2 HZN-825 150mg tablets in the morning and one set of 2 HZN-825 150mg tablets in the evening.

    Drug: HZN-825 BID

  • Placebo comparator
    Placebo

    One set of 2 placebo tablets in the morning and one set of 2 placebo tablets in the evening.

    Drug: Placebo

Interventions

  • DrugHZN-825 BID

    300 mg oral tablets BID

  • DrugPlacebo

    Placebo BID

  • DrugHZN-825 QD

    300 mg oral tablets QD

06

What researchers measure

Primary outcomes

  1. Change From Baseline in Forced Vital Capacity Percent (FVC%) Predicted at Week 52

    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.

    Time frame: Baseline and Week 52

Secondary outcomes

  1. Change From Baseline in the Modified Rodnan Skin Score (mRSS) at 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.

    Time frame: Baseline and Week 52

  2. Number of Participants Responding to Treatment Based on the Revised Composite Response Index in Systemic Sclerosis (CRISS 25) at 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.

    Time frame: Baseline to Week 52

  3. Change From Baseline in HAQ-DI at 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.

    Time frame: Baseline and Week 52

  4. Change From Baseline in CGA at 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.

    Time frame: Baseline and Week 52

  5. Change From Baseline in PTGA at 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.

    Time frame: Baseline and Week 52

  6. Change From Baseline in the Physical Effects Subscale of the Scleroderma Skin Patient-reported Outcome (SSPRO-18) at 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 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.

    Time frame: Baseline and Week 52

  7. Change From Baseline in the Physical Limitations Subscale of the SSPRO-18 at 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.

    Time frame: Baseline and Week 52

  8. Number of Participants With an mRSS Decrease of ≥ 5 Points and 25% From Baseline at 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.

    Time frame: Baseline and Week 52

  9. Number of Participants Who Were Responders at 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.

    Time frame: Week 52

  10. Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) and AEs of Special Interest (AESIs)

    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.

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

  11. Number of Participants Who Received Concomitant Medication

    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.

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

  12. Pre- and Post-dose Plasma Concentrations of Fipaxalparant

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

    Time frame: 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)

07

Results

Posted Mar 20, 2026

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.

Participant flow — Overall Study
MilestoneFipaxalparant 300 mg QDFipaxalparant 300 mg BIDPlacebo
Started100101100
Intent to treat (itt) analysis set100101100
Safety analysis set10010299
Pk analysis set10010299
Completed655664
Not completed354536
Withdrew: Study terminated by sponsor282929
Withdrew: Withdrawal by subject7145
Withdrew: Lost to follow-up011
Withdrew: Death011

Outcome measures

SecondaryChange From Baseline in the Modified Rodnan Skin Score (mRSS) at 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.

Time frame:
Baseline and Week 52
Reported as:
Least squares mean · Score on a scale
Change From Baseline in the Modified Rodnan Skin Score (mRSS) at Week 52
Score on a scaleFipaxalparant 300 mg QDFipaxalparant 300 mg BIDPlacebo
Change From Baseline in the Modified Rodnan Skin Score (mRSS) at Week 52-9.3 ± 0.9-10.7 ± 0.9-8.8 ± 0.9
Statistical analysis
  • Fipaxalparant 300 mg QD vs Placebo · MMRM · p = 0.690 · Ls mean difference: -0.5 · 95% CI -3.0 to 2.0Fipaxalparant QD - Placebo
  • Fipaxalparant 300 mg BID vs Placebo · MMRM · p = 0.157 · Ls mean difference: -1.8 · 95% CI -4.4 to 0.7Fipaxalparant BID - Placebo
SecondaryNumber of Participants Responding to Treatment Based on the Revised Composite Response Index in Systemic Sclerosis (CRISS 25) at 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.

Time frame:
Baseline to Week 52
Reported as:
Count of participants · Participants
Number of Participants Responding to Treatment Based on the Revised Composite Response Index in Systemic Sclerosis (CRISS 25) at Week 52
ParticipantsFipaxalparant 300 mg QDFipaxalparant 300 mg BIDPlacebo
Number of Participants Responding to Treatment Based on the Revised Composite Response Index in Systemic Sclerosis (CRISS 25) at Week 52322733
Statistical analysis
  • Fipaxalparant 300 mg QD vs Placebo · Regression, Logistic · p = 0.8444 · Rate difference: -1.73 · 95% CI -19.006 to 15.546The placebo group is the reference group for the analysis.
  • Fipaxalparant 300 mg BID vs Placebo · Regression, Logistic · p = 0.5526 · Rate difference: -5.343 · 95% CI -22.975 to 12.289The placebo group is the reference group for the analysis.
SecondaryChange From Baseline in HAQ-DI at 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.

Time frame:
Baseline and Week 52
Reported as:
Least squares mean · Score on a scale
Change From Baseline in HAQ-DI at Week 52
Score on a scaleFipaxalparant 300 mg QDFipaxalparant 300 mg BIDPlacebo
Change From Baseline in HAQ-DI at Week 52-0.19 ± 0.063-0.17 ± 0.065-0.24 ± 0.063
Statistical analysis
  • Fipaxalparant 300 mg QD vs Placebo · MMRM · p = 0.5520 · Ls mean difference: 0.05 · 95% CI -0.12 to 0.23Fipaxalparant QD - Placebo
  • Fipaxalparant 300 mg BID vs Placebo · MMRM · p = 0.4303 · Ls mean difference: 0.07 · 95% CI -0.11 to 0.25Fipaxalparant BID - Placebo
SecondaryChange From Baseline in CGA at 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.

Time frame:
Baseline and Week 52
Reported as:
Least squares mean · Score on a scale
Change From Baseline in CGA at Week 52
Score on a scaleFipaxalparant 300 mg QDFipaxalparant 300 mg BIDPlacebo
Change From Baseline in CGA at Week 52-1.8 ± 0.25-2.3 ± 0.26-1.8 ± 0.25
Statistical analysis
  • Fipaxalparant 300 mg QD vs Placebo · MMRM · p = 0.8236 · Ls mean difference: 0.1 · 95% CI -0.6 to 0.8Fipaxalparant QD - Placebo
  • Fipaxalparant 300 mg BID vs Placebo · MMRM · p = 0.1976 · Ls mean difference: -0.5 · 95% CI -1.2 to 0.2Fipaxalparant BID - Placebo
SecondaryChange From Baseline in PTGA at 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.

Time frame:
Baseline and Week 52
Reported as:
Least squares mean · Score on a scale
Change From Baseline in PTGA at Week 52
Score on a scaleFipaxalparant 300 mg QDFipaxalparant 300 mg BIDPlacebo
Change From Baseline in PTGA at Week 52-0.6 ± 0.27-0.4 ± 0.29-1.2 ± 0.28
Statistical analysis
  • Fipaxalparant 300 mg QD vs Placebo · MMRM · p = 0.1235 · Ls mean difference: 0.6 · 95% CI -0.2 to 1.4Fipaxalparant QD - Placebo
  • Fipaxalparant 300 mg BID vs Placebo · MMRM · p = 0.0548 · Ls mean difference: 0.8 · 95% CI -0.0 to 1.5Fipaxalparant BID - Placebo
SecondaryChange From Baseline in the Physical Effects Subscale of the Scleroderma Skin Patient-reported Outcome (SSPRO-18) at 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 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.

Time frame:
Baseline and Week 52
Reported as:
Least squares mean · Score on a scale
Change From Baseline in the Physical Effects Subscale of the Scleroderma Skin Patient-reported Outcome (SSPRO-18) at Week 52
Score on a scaleFipaxalparant 300 mg QDFipaxalparant 300 mg BIDPlacebo
Change From Baseline in the Physical Effects Subscale of the Scleroderma Skin Patient-reported Outcome (SSPRO-18) at Week 52-13.35 ± 2.544-16.12 ± 2.621-14.0 ± 2.551
Statistical analysis
  • Fipaxalparant 300 mg QD vs Placebo · MMRM · p = 0.8471 · Ls mean difference: 0.69 · 95% CI -6.36 to 7.74Fipaxalparant QD - Placebo
  • Fipaxalparant 300 mg BID vs Placebo · MMRM · p = 0.5670 · Ls mean difference: -2.08 · 95% CI -9.25 to 5.08Estimated from a mixed effect repeated measurement analysis with unstructured variance-covariance matrix.
SecondaryChange From Baseline in the Physical Limitations Subscale of the SSPRO-18 at 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.

Time frame:
Baseline and Week 52
Reported as:
Least squares mean · Score on a scale
Change From Baseline in the Physical Limitations Subscale of the SSPRO-18 at Week 52
Score on a scaleFipaxalparant 300 mg QDFipaxalparant 300 mg BIDPlacebo
Change From Baseline in the Physical Limitations Subscale of the SSPRO-18 at Week 52-16.67 ± 2.633-20.15 ± 2.713-17.94 ± 2.639
Statistical analysis
  • Fipaxalparant 300 mg QD vs Placebo · MMRM · p = 0.7317 · Ls mean difference: 1.27 · 95% CI -6.02 to 8.57Fipaxalparant QD - Placebo
  • Fipaxalparant 300 mg BID vs Placebo · MMRM · p = 0.5577 · Ls mean difference: -2.21 · 95% CI -9.62 to 5.21Fipaxalparant BID - Placebo
SecondaryNumber of Participants With an mRSS Decrease of ≥ 5 Points and 25% From Baseline at 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.

Time frame:
Baseline and Week 52
Reported as:
Count of participants · Participants
Number of Participants With an mRSS Decrease of ≥ 5 Points and 25% From Baseline at Week 52
ParticipantsFipaxalparant 300 mg QDFipaxalparant 300 mg BIDPlacebo
Number of Participants With an mRSS Decrease of ≥ 5 Points and 25% From Baseline at Week 52433741
Statistical analysis
  • Fipaxalparant 300 mg QD vs Placebo · Regression, Logistic · p = 0.7806 · Rate difference: 2.390 · 95% CI -14.424 to 19.203
  • Fipaxalparant 300 mg BID vs Placebo · Regression, Logistic · p = 0.7316 · Rate difference: 2.978 · 95% CI -14.038 to 19.995
SecondaryNumber of Participants Who Were Responders at 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.

Time frame:
Week 52
Reported as:
Count of participants · Participants
Number of Participants Who Were Responders at Week 52
ParticipantsFipaxalparant 300 mg QDFipaxalparant 300 mg BIDPlacebo
Number of Participants Who Were Responders at Week 52413333
Statistical analysis
  • Fipaxalparant 300 mg QD vs Placebo · Regression, Logistic · p = 0.1482 · Rate difference: 12.474 · 95% CI -4.434 to 29.382
  • Fipaxalparant 300 mg BID vs Placebo · Regression, Logistic · p = 0.5577 · Rate difference: 5.253 · 95% CI -12.308 to 22.814
SecondaryNumber of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) and AEs of Special Interest (AESIs)

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.

Time frame:
From first dose to last dose + 28 days, median (min, max) duration was 12.8 (1.0, 13.9) months
Reported as:
Count of participants · Participants
Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) and AEs of Special Interest (AESIs)
ParticipantsFipaxalparant 300 mg QDFipaxalparant 300 mg BIDPlacebo
TEAEs878479
AESI302
SecondaryNumber of Participants Who Received Concomitant Medication

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.

Time frame:
From first dose to last dose + 28 days, median (min, max) duration was 12.8 (1.0, 13.9) months
Reported as:
Count of participants · Participants
Number of Participants Who Received Concomitant Medication
ParticipantsFipaxalparant 300 mg QDFipaxalparant 300 mg BIDPlacebo
Number of Participants Who Received Concomitant Medication10010297
SecondaryPre- and Post-dose Plasma Concentrations of Fipaxalparant

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

Time frame:
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)
Reported as:
Mean · ng/mL
Pre- and Post-dose Plasma Concentrations of Fipaxalparant
ng/mLFipaxalparant 300 mg QDFipaxalparant 300 mg BID
Day 1 (post-dose)14800 ± 1010017100 ± 15200
Week 4 (pre-dose)5840 ± 703015600 ± 11200
Week 10 (pre or post-dose)5690 ± 764016300 ± 11600
Week 16 (pre-dose)4540 ± 576013300 ± 8660
Week 16 (post-dose)16500 ± 966022100 ± 13100
Week 28 (pre-dose)3890 ± 422013600 ± 10800
Week 28 (post-dose)17000 ± 1150022800 ± 13900
Week 40 (pre-dose)4960 ± 631014400 ± 11900
Week 52 (pre-dose)3420 ± 466011700 ± 10800
PrimaryChange From Baseline in Forced Vital Capacity Percent (FVC%) Predicted at Week 52

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.

Time frame:
Baseline and Week 52
Reported as:
Least squares mean · % predicted FVC
Change From Baseline in Forced Vital Capacity Percent (FVC%) Predicted at Week 52
% predicted FVCFipaxalparant 300 mg QDFipaxalparant 300 mg BIDPlacebo
Change From Baseline in Forced Vital Capacity Percent (FVC%) Predicted at Week 52-2.35 ± 0.94-3.22 ± 0.98-2.35 ± 0.94
Statistical analysis
  • Fipaxalparant 300 mg QD vs Placebo · Mixed model repeated measures (MMRM) · p = 1.000 · Least squares (ls) mean difference: 0.00 · 95% CI -2.61 to 2.62Fipaxalparant QD - Placebo
  • Fipaxalparant 300 mg BID vs Placebo · MMRM · p = 0.525 · Ls mean difference: -0.87 · 95% CI -3.55 to 1.82Fipaxalparant BID - Placebo

Adverse events

Collected over 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.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Fipaxalparant 300 mg QD0/100 (0%)9/100 (9%)58/100 (58%)
Fipaxalparant 300 mg BID1/101 (1%)8/102 (7.8%)47/102 (46.1%)
Placebo1/100 (1%)5/99 (5.1%)53/99 (53.5%)
Most frequent serious events
Showing 10 of 37
Most frequent serious events
EventFipaxalparant 300 mg QDFipaxalparant 300 mg BIDPlacebo
AppendicitisInfections and infestations2/1000/1020/99
Adrenal insufficiencyEndocrine disorders0/1000/1021/99
EnteritisGastrointestinal disorders0/1000/1021/99
PneumoniaInfections and infestations1/1000/1021/99
OsteonecrosisMusculoskeletal and connective tissue disorders1/1000/1021/99
Acute respiratory failureRespiratory, thoracic and mediastinal disorders0/1000/1021/99
Pneumonia aspirationRespiratory, thoracic and mediastinal disorders0/1000/1021/99
Raynaud's phenomenonVascular disorders0/1001/1021/99
Atrial fibrillationCardiac disorders1/1000/1020/99
Cardiac failureCardiac disorders1/1000/1020/99
Most frequent other events
Showing 10 of 13
Most frequent other events
EventFipaxalparant 300 mg QDFipaxalparant 300 mg BIDPlacebo
Urinary tract infectionInfections and infestations16/1007/1027/99
DiarrhoeaGastrointestinal disorders7/1003/10213/99
ArthralgiaMusculoskeletal and connective tissue disorders6/1002/10211/99
COVID-19Infections and infestations10/1006/1029/99
Upper respiratory tract infectionInfections and infestations6/10010/1026/99
NasopharyngitisInfections and infestations7/1006/1028/99
HeadacheNervous system disorders7/1005/1024/99
VomitingGastrointestinal disorders3/1002/1026/99
GastroenteritisInfections and infestations5/1005/1026/99
Skin ulcerSkin and subcutaneous tissue disorders6/1002/1026/99

Baseline characteristics

ITT Analysis Set: participants who were randomized to a treatment regardless of whether they received trial drug or not. Treatment group assignment was based on the randomized treatment.

Age, Categorical
Age, Categorical(Participants)Fipaxalparant 300 mg QDFipaxalparant 300 mg BIDPlaceboTotal
<=18 years0000
Between 18 and 65 years868790263
>=65 years14141038
Sex: Female, Male
Sex: Female, Male(Participants)Fipaxalparant 300 mg QDFipaxalparant 300 mg BIDPlaceboTotal
Female767880234
Male24232067
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Fipaxalparant 300 mg QDFipaxalparant 300 mg BIDPlaceboTotal
Hispanic or Latino403342115
Not Hispanic or Latino606858186
Unknown or Not Reported0000
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)Fipaxalparant 300 mg QDFipaxalparant 300 mg BIDPlaceboTotal
American Indian or Alaska Native0123
Asian9111434
Black or African American4239
Native Hawaiian or Other Pacific Islander0213
White857677238
Other28212
Unknown or not reported0112
08

Study locations

4 sites
  • Institute of Rheumatology - PPDS
    Belgrade, 11000, Serbia
  • Military Medical Academy
    Belgrade, 11000, Serbia
  • Institute for Treatment and Rehabilitation Niska Banja
    Niška Banja, 708120, Serbia
  • Hospital de La Santa Creu i Sant Pau
    Barcelona, 08025, Spain
09

References and documents

Study documents

  • Study protocol · Aug 22, 2024
  • Statistical analysis plan · Oct 28, 2024

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.

Supporting information: Study protocol, Sap, Icf, Csr

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Mar 20, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT04781543
Lead sponsor
Amgen
Responsible party
Sponsor
First posted
Mar 4, 2021
Start date
Nov 5, 2021
Primary completion
Feb 24, 2025
Completion
Feb 24, 2025
Results posted
Mar 20, 2026
Last update
Mar 20, 2026

Study contacts

MD
study director · Amgen

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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