Diffuse Cutaneous Systemic Sclerosis, Sclerosis, Systemic
Conditions
Keywords
Scleroderma, Forced vital capacity
Brief summary
Primary Objectives: 1. The primary efficacy objective is to assess the efficacy of 52 weeks of open-label treatment with HZN-825 in participants with diffuse cutaneous systemic sclerosis, as measured by change from both baselines in forced vital capacity percent (FVC %) predicted. 2. The primary safety objective is to examine the safety and tolerability of 52 weeks of open-label treatment with HZN-825, inclusive of, but not limited to, adverse events (AEs), serious AEs (SAEs) and the adverse event of special interest (AESI), from Day 1 to 4 weeks after last dose.
Detailed description
This is an open-label, repeat-dose, multicenter extension trial of HZNP-HZN-825-301. Participants who complete the double-blind Treatment Period (Week 52) in Trial HZNP-HZN-825-301 will be eligible to enter this 52-week extension trial. Participants entering this extension trial will complete the Week 52 Visit activities in HZNP-HZN-825-301 and will not complete the Safety Follow-up Visit 4 weeks after the last dose of trial drug in HZNP-HZN-825-301. Acquired from Horizon in 2024.
Interventions
DRUGHZN-825
HZN-825 will be administered BID for 52 weeks
Sponsors
Amgen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1\. Completed the double-blind Treatment Period (Week 52) in Trial HZNP-HZN-825-301; participants prematurely discontinued from trial drug in Trial HZNP-HZN-825-301 for reasons other than safety or toxicity can be included at the discretion of the Investigator after completing Trial HZNP-HZN-825-301 scheduled visits, including Week 52 assessments. Key
Exclusion criteria
1. Anticipated use of another investigational agent for any condition during the course of the trial. 2. New diagnosis of malignant condition after enrolling in Trial HZNP-HZN-825-301 (except successfully treated basal/squamous cell carcinoma of the skin or cervical cancer in situ). 3. Women of childbearing potential (WOCBP) or male participants not agreeing to use highly effective method(s) of birth control throughout the trial and for 4 weeks after last dose of trial drug as defined in the protocol. 4. Any new development with the participant's disease or condition or any significant laboratory test abnormality during the course of Trial HZNP-HZN-825-301 that, in the opinion of the Investigator, would potentially put the subject at unacceptable risk. 5. Pregnant or lactating women. 6. Participants will be ineligible if, in the opinion of the Investigator, they are unlikely to comply with the trial protocol or have a concomitant disease or condition that could interfere with the conduct of the trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Forced Vital Capacity Percentage (FVC%) Predicted at Week 52 | Baseline and Week 52 | FVC is the amount of air that can be forcibly exhaled from the lungs after taking the deepest breath possible, as measured by spirometry. FVC is a measure of respiratory function. 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. |
| Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | From 1st dose to last dose + 28 days; median (min, max) time on trial was 8.5 (1.0, 14.0) months | An adverse event (AE) was defined as any untoward medical occurrence in a trial participant who received an investigational product (IP), regardless of a causal relationship with treatment. An AE could be any unfavorable and unintended sign (including abnormal laboratory findings), symptom, or disease temporally associated with the use of an IP. TEAEs were defined as events that began or worsened in severity on or after the first dose of treatment through 28 days after the last dose or the cutoff date for ongoing participants. Serious TEAEs were those that resulted in death, were life-threatening, required or prolonged hospitalization, caused significant disability/incapacity, led to a congenital anomaly/birth defect, or were considered other important medical events. Clinically significant changes in vital signs, electrocardiograms (ECGs), and laboratory tests were included as TEAEs. |
| Number of Participants Who Experienced AEs of Special Interest (AESI) | Day 1 and at Weeks 4, 28 and 52 | The following AESI was identified for this trial: Orthostatic hypotension defined as a reduction of systolic blood pressure by ≥20 mmHg or reduction of diastolic blood pressure by ≥10 mmHg and associated with symptoms such as lightheadedness, blurred vision, weakness, fatigue, cognitive impairment, nausea, palpitations, tremulousness, headache, presyncope or syncope. |
| Number of Participants Using Any Concomitant Medication | From 1st dose to last dose + 28 days; median (min, max) time on trial was 8.5 (1.0, 14.0) months | Concomitant medications were defined as any medication that was ongoing, had a start date on or after the first dose of the trial drug, or had a stop date on or after the first dose date. |
Countries
Argentina, Chile, Greece, Israel, Italy, Japan, Mexico, Poland, Portugal, Romania, Serbia, South Korea, Spain, United Kingdom, United States
Participant flow
Recruitment details
Participants were enrolled at 77 research centers in Argentina, Austria, Chile, France, Germany, Greece, Israel, Italy, Japan, South Korea, Mexico, Poland, Portugal, Romania, Serbia, Spain, Switzerland, the United Kingdom, and the United States between November 2022 to February 2025.
Pre-assignment details
This trial is an open-label extension (OLE) of the parent trial HZNP-HZN-825-301, in which participants received either HZN-825 300 mg twice daily (BID), HZN-825 300 mg once daily (QD), or placebo. Participants in this OLE trial all received the same dose regimen: open-label HZN-825 300 mg BID, orally, for 52 weeks. Participants are analyzed according to the group determined by the treatment received in the parent trial.
Participants by arm
| Arm | Count |
|---|---|
| HZN-825 300 mg QD in Parent Trial Participants who received HZN-825 300 mg QD in the parent trial received HZN-825 300 mg orally BID in this OLE extension for 52 weeks. | 62 |
| HZN-825 300 mg BID in Parent Trial Participants who received HZN-825 300 mg BID in parent trial continued to receive HZN-825 300 mg orally BID in this OLE extension for 52 weeks. | 52 |
| Placebo in Parent Trial Participants who received Placebo in parent trial received HZN-825 300 mg orally BID in this OLE extension for 52 weeks. | 60 |
| Total | 174 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 2 | 1 |
| Overall Study | Trial Terminated by Sponsor | 39 | 30 | 37 |
| Overall Study | Withdrawal by Subject | 7 | 5 | 5 |
Baseline characteristics
| Characteristic | HZN-825 300 mg QD in Parent Trial | HZN-825 300 mg BID in Parent Trial | Placebo in Parent Trial | Total |
|---|---|---|---|---|
| Age, Continuous | 48.9 years STANDARD_DEVIATION 12.7 | 49.8 years STANDARD_DEVIATION 11.2 | 48.5 years STANDARD_DEVIATION 12.4 | 49.0 years STANDARD_DEVIATION 12.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 26 Participants | 20 Participants | 25 Participants | 71 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 36 Participants | 32 Participants | 35 Participants | 103 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 7 Participants | 9 Participants | 21 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 1 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 6 Participants | 3 Participants | 10 Participants |
| Race (NIH/OMB) White | 54 Participants | 36 Participants | 44 Participants | 134 Participants |
| Sex: Female, Male Female | 46 Participants | 44 Participants | 50 Participants | 140 Participants |
| Sex: Female, Male Male | 16 Participants | 8 Participants | 10 Participants | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 62 | 0 / 52 | 0 / 60 |
| other Total, other adverse events | 17 / 62 | 18 / 53 | 20 / 59 |
| serious Total, serious adverse events | 2 / 62 | 2 / 53 | 5 / 59 |
Outcome results
Primary
Change From Baseline in Forced Vital Capacity Percentage (FVC%) Predicted at Week 52
FVC is the amount of air that can be forcibly exhaled from the lungs after taking the deepest breath possible, as measured by spirometry. FVC is a measure of respiratory function. 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
Population: The FAS included all participants who were enrolled and received at least one full or partial dose of HZN-825 in this extension trial. Only participants with available data were included in this endpoint. Participants were analyzed according to the group determined by the treatment that the participant received in the parent trial HZNP-HZN-825-301.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HZN-825 300 mg QD in Parent Trial | Change From Baseline in Forced Vital Capacity Percentage (FVC%) Predicted at Week 52 | -1.36 % predicted FVC | Standard Deviation 8.46 |
| HZN-825 300 mg BID in Parent Trial | Change From Baseline in Forced Vital Capacity Percentage (FVC%) Predicted at Week 52 | -7.95 % predicted FVC | Standard Deviation 15.36 |
| Placebo in Parent Trial | Change From Baseline in Forced Vital Capacity Percentage (FVC%) Predicted at Week 52 | -0.82 % predicted FVC | Standard Deviation 4.09 |
Primary
Number of Participants Using Any Concomitant Medication
Concomitant medications were defined as any medication that was ongoing, had a start date on or after the first dose of the trial drug, or had a stop date on or after the first dose date.
Time frame: From 1st dose to last dose + 28 days; median (min, max) time on trial was 8.5 (1.0, 14.0) months
Population: The SAS included all participants who had received at least one dose or partial dose of HZN-825 in the extension trial.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HZN-825 300 mg QD in Parent Trial | Number of Participants Using Any Concomitant Medication | 62 Participants |
| HZN-825 300 mg BID in Parent Trial | Number of Participants Using Any Concomitant Medication | 52 Participants |
| Placebo in Parent Trial | Number of Participants Using Any Concomitant Medication | 58 Participants |
Primary
Number of Participants Who Experienced AEs of Special Interest (AESI)
The following AESI was identified for this trial: Orthostatic hypotension defined as a reduction of systolic blood pressure by ≥20 mmHg or reduction of diastolic blood pressure by ≥10 mmHg and associated with symptoms such as lightheadedness, blurred vision, weakness, fatigue, cognitive impairment, nausea, palpitations, tremulousness, headache, presyncope or syncope.
Time frame: Day 1 and at Weeks 4, 28 and 52
Population: The SAS included all participants who had received at least one dose or partial dose of HZN-825 in the extension trial.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HZN-825 300 mg QD in Parent Trial | Number of Participants Who Experienced AEs of Special Interest (AESI) | 0 Participants |
| HZN-825 300 mg BID in Parent Trial | Number of Participants Who Experienced AEs of Special Interest (AESI) | 0 Participants |
| Placebo in Parent Trial | Number of Participants Who Experienced AEs of Special Interest (AESI) | 0 Participants |
Primary
Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
An adverse event (AE) was defined as any untoward medical occurrence in a trial participant who received an investigational product (IP), regardless of a causal relationship with treatment. An AE could be any unfavorable and unintended sign (including abnormal laboratory findings), symptom, or disease temporally associated with the use of an IP. TEAEs were defined as events that began or worsened in severity on or after the first dose of treatment through 28 days after the last dose or the cutoff date for ongoing participants. Serious TEAEs were those that resulted in death, were life-threatening, required or prolonged hospitalization, caused significant disability/incapacity, led to a congenital anomaly/birth defect, or were considered other important medical events. Clinically significant changes in vital signs, electrocardiograms (ECGs), and laboratory tests were included as TEAEs.
Time frame: From 1st dose to last dose + 28 days; median (min, max) time on trial was 8.5 (1.0, 14.0) months
Population: The safety analysis set (SAS) included all participants who had received at least one dose or partial dose of HZN-825 in the extension trial.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| HZN-825 300 mg QD in Parent Trial | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | TEAEs | 34 Participants |
| HZN-825 300 mg QD in Parent Trial | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Serious TEAEs | 2 Participants |
| HZN-825 300 mg BID in Parent Trial | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | TEAEs | 37 Participants |
| HZN-825 300 mg BID in Parent Trial | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Serious TEAEs | 2 Participants |
| Placebo in Parent Trial | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | TEAEs | 35 Participants |
| Placebo in Parent Trial | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Serious TEAEs | 5 Participants |