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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

Sponsor
Horizon Therapeutics Ireland DAC (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04781543
Collaborator
(none)
300
Enrollment
71
Locations
3
Arms
27
Anticipated Duration (Months)
4.2
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

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, NCT not available yet). 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
  • Drug: HZN-825 BID
  • Drug: Placebo
  • Drug: HZN-825 QD
 Phase 2

Study Design

Study Type:
Interventional
Anticipated 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 :
Apr 1, 2021
Anticipated Primary Completion Date :
Jul 1, 2023
Anticipated Study Completion Date :
Jul 1, 2023

Arms and Interventions

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

Primary Outcome Measures

  1. Change in FVC (forced vital capacity) percent predicted from Baseline to Week 52 [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 [Baseline to Week 52]

  2. Change from Baseline in MDGA (Physician Global Assessment) at Week 52 [Baseline to Week 52]

  3. Change from Baseline in PTGA (Patient Global Assessment) at Week 52 [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 [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 [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 [Baseline to Week 52]

  7. Responder rate (defined as ACR-CRISS [predicted probability] of at least 0.6) at Week 52 [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) [Baseline to Week 52]

    American College of Rheumatology-Composite Response Index in Systemic Sclerosis

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 75 Years
Sexes Eligible for Study:
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 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:

  6. uncontrolled, severe hypertension (≥160/100 mmHg) or persistent low blood pressure (systolic blood pressure <90 mmHg) within 6 months of Screening,

  7. myocardial infarction within 6 months of Screening,

  8. unstable cardiac angina within 6 months of Screening.

  9. 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.

  10. 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.

  11. 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).

  12. 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.

  13. Known active bacterial, viral, fungal, mycobacterial or other infection, including tuberculosis or atypical mycobacterial disease (fungal infections of nail beds are allowed).

  14. 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.

  15. Malignant condition in the past 5 years (except successfully treated basal/squamous cell carcinoma of the skin or cervical cancer in situ).

  16. 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.

  17. Pregnant or lactating women.

  18. 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.

  19. Previous enrollment in this trial or participation in a prior HZN-825 or SAR100842 clinical trial.

  20. Known history of positive test for human immunodeficiency virus.

  21. 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).

  22. Current alcoholic liver disease, primary biliary cirrhosis or primary sclerosing cholangitis.

  23. Previous organ transplant (including allogeneic and autologous marrow transplant).

  24. International normalized ratio >2, prolonged prothrombin time >1.5 × the upper limit of normal (ULN) or partial thromboplastin time >1.5 × ULN at Screening.

  25. Alanine aminotransferase or aspartate aminotransferase >2 × ULN.

  26. Estimated glomerular filtration rate <30 mL/min/1.73 m^2 at Screening.

  27. Total bilirubin >2 × ULN. Subjects with documented diagnosis of Gilbert's syndrome may be enrolled if their total bilirubin is ≤3.0 mg/dL.

  28. Any other condition that, in the opinion of the Investigator, would preclude enrollment in the trial.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Arizona Arthritis and Rheumatology Research, PLLC Phoenix Arizona United States 85032
2 Pacific Arthritis Care Center Los Angeles California United States 90045
3 UCLA Department of Medicine Los Angeles California United States 90095-1670
4 IRIS Research and Development LLC Plantation Florida United States 33324
5 DelRicht Clinical Research, LLC New Orleans Louisiana United States 70115
6 Boston University School Of Medicine Boston Massachusetts United States 02118-2642
7 Michigan Medicine University of Michigan Ann Arbor Michigan United States 48109
8 Mayo Clinic - Cancer Center Rochester Minnesota United States 55905
9 Medical University of South Carolina Charleston South Carolina United States 29425-8900
10 Metroplex Clinical Research Center Dallas Texas United States 75231
11 UT Physicians Rheumatology Houston Texas United States 77030
12 Framingham Centro Médico La Plata Buenos Aires Argentina B1902COS
13 Consultorios Médicos Dr. Catalán Pellet Recoleta Ciudad Autónoma De BuenosAires Argentina C1111AAL
14 Centro de Investigaciones Médicas Tucumán San Miguel de Tucuman Tucumán Argentina T4000AXL
15 Consultorio de Investigaciones Reumatologicas San Miguel De Tucumán Tucumán Argentina T4000AXL
16 Clinica Mayo de U.M.C.B. S.R.L San Miguel de Tucumán Tucumán Argentina T4000
17 Organización Médica de Investigación Ciudad Autónoma de Buenos Aires Argentina C1015
18 Aprillus Asistencia e Investigacion de Arcis Salud SRL Ciudad Autónoma de Buenos Aires Argentina C1406AGA
19 Consultorio Médico Dra. Rivera Ciudad Autónoma de Buenos Aires Argentina C1426
20 Clínica Adventista Belgrano Ciudad Autónoma de Buenos Aires Argentina C1430
21 I.R. Medical Center - Hospital de Dia Mendoza Argentina M5500CPH
22 Medizinische Universität Graz Graz Steiermark Austria 8010
23 Hôpitaux Universitaires de Strasbourg Strasbourg Bas-Rhin France 67000
24 Centre Hospitalier Universitaire de Bordeaux, Hopital Pellegrin Bordeaux Gironde France 33000
25 Hôpital de Rangueil Toulouse Haute-Garonne France 31000
26 Hôpital Claude Huriez Lille Nord France 59000
27 Hopital Cochin Paris France 75014
28 Charité - Universitätsmedizin Berlin Berlin Germany 10117
29 Laiko General Hospital of Athens Athens Attiki Greece 115 27
30 Kianous Stavros Thessaloniki Greece 546 36
31 Ippokratio General Hospital of Thessaloniki Thessaloniki Greece 564 29
32 Meir Medical Center Kfar Sava HaMerkaz Israel 44281
33 Tel Aviv Sourasky Medical Center Tel Aviv-Yafo Tel-Aviv Israel 64239
34 Rambam Medical Center Haifa Israel 31096
35 Lady Davis Carmel Medical Center Haifa Israel 34362
36 Sheba Medical Center Tel HaShomer Israel 52621
37 Fondazione Policlinico Universitario A Gemelli Roma Lazio Italy 00168
38 Fondazione IRCCS Policlinico San Matteo di Pavia Pavia Lombardia Italy 27100
39 Azienda Ospedaliera Universitaria Careggi Firenze Toscana Italy 50141
40 Saitama Medical University Hospital Iruma-Gun Saitama Japan 350-0495
41 Nippon Medical School Hospital Tokyo Japan 113-8603
42 Seoul National University Bundang Hospital Seongnam Gyeonggido Korea, Republic of 13620
43 Chonnam National University Hospital Gwangju Korea, Republic of 61469
44 Hanyang University Medical Center Seoul Korea, Republic of 4763
45 Gangnam Severance Hospital, Yonsei University Health System Seoul Korea, Republic of 6273
46 CITER, Centro de Investigacion y Tratamiento de las Enfermedades Reumaticas SA de CV Mexico Distrito Federal Mexico 6700
47 Centro de Investigación y Tratamiento Reumatológico S.C Miguel Hidalgo Distrito Federal Mexico 11850
48 Centro de Estudios de Investigacion Basica Y Clinica SC Guadalajara Jalisco Mexico 44690
49 Centro Integral Reumatologia SA de CV Guadalajara Jalisco Mexico ZC 44160
50 Centro de Alta Especialidad En Reumatologia E Investigacion Del Potosi SC Burócratas del Estado San Luis Potosí Mexico 78213
51 Unidad de Atencion Medica e Investigacion en Salud Merida Yucatán Mexico 97000
52 Clinica de Investigacion en Reumatologia y Obesidad Guadalajara Mexico 44650
53 Leids Universitair Medisch Centrum Leiden Zuid-Holland Netherlands 2333 ZA
54 Universitair Medisch Centrum Groningen Groningen Netherlands 9713 GZ
55 Twoja Przychodnia NCM Nowa Sól Lubuskie Poland 67-100
56 Medicover Integrated Clinical Services sp. z o.o Warszawa Mazowieckie Poland 00-874
57 MCM Krakow - PRATIA Kraków Poland 30-510
58 Hospital Garcia de Orta Almada Setúbal Portugal 2805-267
59 Hospital de Braga Braga Portugal 4710-243
60 Centro Hospitalar E Universitário de Coimbra EPE Coimbra Portugal 3000-459
61 Centro Hospitalar Lisboa Norte, E.P.E. - Hospital de Santa Maria Lisboa Portugal 1649-035
62 Hospital Conde de Bertiandos Unidade Local de Saúde Do Alto Minho Ponte De Lima Portugal 4990-041
63 Centro Hospitalar de São João, E.P.E. Porto Portugal 4200-319
64 Hospital de Merida Merida Badajoz Spain 6800
65 Corporacio Sanitaria Parc Tauli Sabadell Barcelona Spain 8208
66 C.H. Regional Reina Sofia Cordoba Córdoba Spain 14004
67 Hospital Universitario Vall d'Hebron Barcelona Spain 008035
68 Hospital de La Santa Creu i Sant Pau Barcelona Spain 8025
69 Hospital Quironsalud Infanta Luisa Sevilla Spain 41010
70 Hospital Universitario Virgen del Rocio Sevilla Spain 41013
71 Hospital Universitario Doctor Peset Valencia Spain 46017

Sponsors and Collaborators

  • Horizon Therapeutics Ireland DAC

Investigators

  • Study Director: Farah Ali, MD, Horizon Therapeutics

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Horizon Therapeutics Ireland DAC
ClinicalTrials.gov Identifier:
NCT04781543
Other Study ID Numbers:
  • HZNP-HZN-825-301
  • 2020-005764-62
First Posted:
Mar 4, 2021
Last Update Posted:
Aug 25, 2022
Last Verified:
Aug 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Undecided
Plan to Share IPD:
Undecided
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Horizon Therapeutics Ireland DAC
Scleroderma
Additional relevant MeSH terms:
Scleroderma, Systemic
Scleroderma, Diffuse
Sclerosis

Study Results

No Results Posted as of Aug 25, 2022