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

• Register: EUCTR
• Last refreshed on: 8 July 2024
• Main ID: EUCTR2020-005764-62-DE
• Date of registration: 14/06/2021
• Prospective Registration: Yes
• Primary sponsor: Horizon Therapeutics Ireland DAC
• Public title: A Study to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of HZN-825 in Patients with Diffuse Cutaneous Systemic Sclerosis
• Scientific 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
• Date of first enrolment: 09/08/2021
• Target sample size: 300
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2020-005764-62
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Austria, Chile, France, Germany, Greece, Israel, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Poland, Portugal, Romania, Serbia, Spain, Switzerland, United Kingdom, United States

Contacts

• Name: Arati Kanchi
• Affiliation: Horizon Therapeutics U.S.A., Inc.

• Name: Arati Kanchi
• Affiliation: Horizon Therapeutics U.S.A., Inc.

Key inclusion & exclusion 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/or 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 in the forearm suitable for repeat biopsy (only applicable to the first 110 subjects for whom biopsy will be performed).
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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 285
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 15

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 w/sine scleroderma or limited cutaneous SSc.
3.Diagnosed w/other autoimmune connective tissue diseases ,except for fibromyalgia, scleroderma-associated myopathy & secondary Sjogren's syndrome.
4.Scleroderma renal crisis diagnosed within6months of the Screening Visit.
5.Any of the following cardiovascular diseases: a. uncontrolled, severe hypertension(=160/100mmHg)or persistent low blood pressure (systolic blood pressure<90 mmHg)within6months of Screening, b. myocardial infarction within6months of Screening, c. unstable cardiac angina within6months of Screening.
6.DLCO<40%predicted(corrected for hemoglobin).If severe acute respiratory syndrome coronavirus2 (SARS-CoV-2) exposure is of clinical concern for any subject, consider using a DLCO up to6months before the Screening Visit.
7.Pulmonary arterial hypertension(PAH)by right heart catheterization requiring treatment w/more than1oral 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 within4weeks prior to Screening(topical steroids for dermatological conditions& inhaled/intranasal/intra-articular steroids are allowed).
9.Use of any other non-steroid immunosuppressive agent, small biologic molecule, cytotoxic or antifibrotic drug within4weeks prior to 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 =3g/day, Myfortic =2.14g/day, methotrexate =20 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=6months 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 Day1Visit. It is acceptable to be on background low-dose prednisone &anti-malarial drug along with CellCept, Myfortic or methotrexate. Rituximab must not have been used within 6 months of the Day1Visit.Subjects must not be withdrawn from any standard-of-care treatment that is considered necessary for the clinical management of the subject in order to fulfill the trial eligibility requirements.
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 90days or 5half-lives,whichever is longer, prior to Screening or anticipated use during the course of the trial.
12.Malignant condition in the past5years(except successfully treated basal/squamous cell carcinoma of the skin or cervical cancer in situ).
13.Women of childbearing potential (WOCBP) or male subjects not agreeing to use highly effective method(s)of birth control throughout
the trial and for 4 weeks after last dose of trial drug. Male subjects must refrain from sperm donation and females from egg/ova donation for this same time period. Women are conside

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Diffuse Cutaneous Systemic Sclerosis
MedDRA version: 21.0 Level: LLT Classification code 10042953 Term: Systemic sclerosis System Organ Class: 100000004859

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

Product Code: HZN-825
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: HZN-825
Current Sponsor code: HZN-825
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: 1.Evaluate the effect of 2 dose regimens of HZN-825 vs. placebo on
Health Assessment Questionnaire-Disability Index after 52 weeks of
treatment.
2.Evaluate the effect of 2 dose regimens of HZN-825 vs. placebo on
Physician Global Assessment (MDGA) after 52 weeks of treatment.
3.Evaluate the effect of 2 dose regimens of HZN-825 vs. placebo on
Patient Global Assessment (PTGA) after 52 weeks of treatment.
4.Evaluate the effect of 2 dose regimens of HZN-825 vs. placebo on the
Physical Effects subscale of the scleroderma skin patient-reported
outcome after 52 weeks of treatment.
5.Evaluate the effect of 2 dose regimens of HZN-825 vs. placebo on the
Physical Limitations subscale of the SSPRO-18 after 52 weeks of
treatment.
6.Evaluate the effect of 2 dose regimens of HZN-825 vs. placebo on the
modified Rodnan skin score, after 52 weeks of treatment.
7. Evaluate the effect of 2 dose regimens of HZN-825 vs. placebo on ACR-CRISS after 52 weeks of treatment.

Main Objective: The primary objective is to demonstrate the efficacy of 1 or 2 dose regimens of HZN-825 versus placebo in subjects with diffuse cutaneous SSc, as determined by a comparison of change in forced vital capacity (FVC) % predicted after 52 weeks of treatment

Timepoint(s) of evaluation of this end point: From Baseline to Week 52

Primary end point(s): Change in FVC % predicted from Baseline to Week 52

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: From Baseline to Week 52

Secondary end point(s): 1.Change from Baseline in HAQ-DI at Week 52.
2.Change from Baseline in MDGA at Week 52.
3.Change from Baseline in PTGA at Week 52.
4.Change from Baseline in the Physical Effects subscale of the SSPRO-18 at Week 52.
5.Change from Baseline in the Physical Limitations subscale of the SSPRO-18 at Week 52.
6.Proportion of subjects with an mRSS decrease of =5 points and 25% from Baseline at Week 52.
7.Responder rate (defined as ACR-CRISS [predicted probability] of at least 0.6) at Week 52.
8.Proportion of subjects 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).

Secondary ID(s)

2021-02-22/Prot Admin Change 1/HZNP-HZN-825-301

NCT04781543

HZNP-HZN-825-301

2021-07-22/GER/AUT V1.0 Add/HZNP-HZN-825-301

Source(s) of Monetary Support

Horizon Therapeutics USA, Inc

Ethics review

Status: Approved
Approval date: 09/08/2021
Contact: