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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04781543
Recruitment Status : Recruiting
First Posted : March 4, 2021
Last Update Posted : May 12, 2023
Sponsor:
Information provided by (Responsible Party):
Horizon Pharma Ireland, Ltd., Dublin Ireland ( Horizon Therapeutics Ireland DAC )

Study Description
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Brief Summary:

This is a randomized, double-blind, placebo-controlled, repeat-dose, multicenter trial. Participants will be screened within 4 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 4-week Screening Period and a 52-week Double-blind Treatment Period. Participants will take their first dose of trial drug at the clinic and will return to the clinic for 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 will return to the clinic for a Safety Follow-up Visit 4 weeks after the last dose of trial drug.


Condition or disease Intervention/treatment Phase
Diffuse Cutaneous Systemic Sclerosis Sclerosis, Systemic Drug: HZN-825 BID Drug: Placebo Drug: HZN-825 QD Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo-controlled, Repeat-dose, Multicenter Trial to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of HZN-825 in Patients With Diffuse Cutaneous Systemic Sclerosis
Actual Study Start Date : April 1, 2021
Estimated Primary Completion Date : December 2024
Estimated Study Completion Date : December 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Scleroderma

Arms and Interventions
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Arm Intervention/treatment
Experimental: HZN-825 300 mg once daily (QD)
300mg oral tablets given in the morning and placebo in the evening
 Drug: HZN-825 QD
300 mg oral tablets QD
Experimental: HZN-825 300 mg twice daily (BID)
300mg oral tablets given in the morning and evening
 Drug: HZN-825 BID
300 mg oral tablets BID
Placebo Comparator: Placebo
Placebo will be given orally in the morning and evening
 Drug: Placebo
Placebo BID


Outcome Measures
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Primary Outcome Measures :
  1. Change in FVC (forced vital capacity) percent predicted from Baseline to Week 52 [ Time Frame: Baseline to Week 52 ]
    As measured by a pulmonary function test called a spirometry.


Secondary Outcome Measures :
  1. Change from Baseline in HAQ-DI (Health Assessment Questionnaire - Disability Index) at Week 52 [ Time Frame: Baseline to Week 52 ]
  2. Change from Baseline in MDGA (Physician Global Assessment) at Week 52 [ Time Frame: Baseline to Week 52 ]
  3. Change from Baseline in PTGA (Patient Global Assessment) at Week 52 [ Time Frame: Baseline to Week 52 ]
  4. Change from Baseline in the Physical Effects subscale of the scleroderma skin patient-reported outcome (SSPRO-18) at Week 52 [ Time Frame: Baseline to Week 52 ]
  5. Change from Baseline in the Physical Limitations subscale of the scleroderma skin patient-reported outcome SSPRO-18 at Week 52 [ Time Frame: Baseline to Week 52 ]
  6. Proportion of participants with an mRSS (modified Rodnan skin score) decrease of ≥5 points and 25% from Baseline at Week 52 [ Time Frame: Baseline to Week 52 ]
  7. Responder rate (defined as ACR-CRISS [predicted probability] of at least 0.6) at Week 52 [ Time Frame: Week 52 ]
    American College of Rheumatology-Composite Response Index in Systemic Sclerosis

  8. Proportion of participants with an improvement in ≥3 of 5 core measures from Baseline: ≥20% in mRSS, ≥20% in HAQ-DI, ≥20% in PTGA, ≥20% in MDGA and ≥5% for FVC % predicted at Week 52 (ACR-CRISS-20) [ Time Frame: Baseline to Week 52 ]
    American College of Rheumatology-Composite Response Index in Systemic Sclerosis


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 36 months 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:

  1. Positive for anti-centromere antibodies.
  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 ≤15 mg/week and prednisone ≤10 mg/day (or equivalent dosing of glucocorticoids) is allowed. See Table 9.1 for full details. Subjects taking CellCept, Myfortic or methotrexate must have been doing so for ≥6 months and the dose must have been stable for ≥16 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).
  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.
  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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04781543


Contacts
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Contact: HorizonTherapeutics 866-479-6742 clinicaltrials@horizontherapeutics.com

Locations
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Sponsors and Collaborators
Horizon Therapeutics Ireland DAC
Investigators
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Study Director: Farah Ali, MD Horizon Therapeutics
More Information
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Responsible Party: Horizon Therapeutics Ireland DAC
ClinicalTrials.gov Identifier: NCT04781543    
Other Study ID Numbers: HZNP-HZN-825-301
2020-005764-62 ( EudraCT Number )
First Posted: March 4, 2021    Key Record Dates
Last Update Posted: May 12, 2023
Last Verified: May 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Horizon Pharma Ireland, Ltd., Dublin Ireland ( Horizon Therapeutics Ireland DAC ):
Scleroderma
Additional relevant MeSH terms:
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Scleroderma, Systemic
Scleroderma, Diffuse
Sclerosis
 Pathologic Processes
Connective Tissue Diseases
Skin Diseases