A Multicenter, Open-label Extension Trial of HZN-825 in Patients with Diffuse Cutaneous Systemic Sclerosis

JRCT ID: jRCT2011230044

Registered date:24/10/2023

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Diffuse Cutaneous Systemic Sclerosis (Diffuse Cutaneous SSc)
• Date of first enrollment: 07/11/2023
• Target sample size: 21
• Countries of recruitment: ARGENTINA,Japan,AUSTRIA,Japan,CHILE,Japan,FRANCE,Japan,GERMANY,Japan,GREECE,Japan,ISRAEL,Japan,ITALY,Japan,KOREA, REPUBLIC OF,Japan,MEXICO,Japan,NETHERLANDS,Japan,POLAND,Japan,PORTUGAL,Japan,ROMANIA,Japan,SERBIA,Japan,SPAIN,Japan,SWITZERLAND,Japan,UNITED KINGDOM,Japan,UNITED STATES,Japan
• Study type: Interventional
• Intervention(s): The dose regimen for all subjects will be HZN-825 300 mg BID. Subjects will take 2 HZN-825 150 mg tablets orally in the morning and evening with a meal.

Outcome(s)

• Primary Outcome: The primary endpoint is the change from both Baselines in FVC % predicted at Week 52.

Secondary Outcome

1. Change from both Baselines in HAQ-DI at Week 52.
2. Change from both Baselines in MDGA at Week 52.
3. Change from both Baselines in PTGA at Week 52.
4. Change from both Baselines in the Physical Effects subscale of the SSPRO-18 at Week 52.
5. Change from both Baselines in the Physical Limitations subscale of the SSPRO-18 at Week 52.
6. Proportion of subjects with an mRSS decrease of more than or equal to 5 points and 25% from both Baselines 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 more than or equal to 3 of 5 core measures from both Baselines: more than or equal to 20% in mRSS, more than or equal to 20% in HAQ-DI, more than or equal to 20% in PTGA, more than or equal to 20% in MDGA and more than or equal to 5% for FVC % predicted at Week 52 (ACR-CRISS-20).
9. Change from both Baselines in the SSPRO-18 at Week 52.
10. Change from both Baselines in each scale of the UCLA SCTC GIT 2.0 and the total GIT score at Week 52.
11. Change from both Baselines in Raynaud's phenomenon using the Raynaud's Assessment at Week 52.
12. Change from both Baselines in the SHAQ at Week 52.
13. Change from both Baselines in SScQoL scores at Week 52.
14. Change from both Baselines in SF-12 scores at Week 52.
15. Change from both Baselines in pain and pain component scale scores at Week 52.
16. Change from both Baselines in the FACIT-F score at Week 52.
17. Change from both Baselines in the mRSS at Week 52.
18. Change from both Baselines in lung fibrosis based on HRCT at Week 52.
19. Change from both Baselines in DLCO at Week 52.
20. Change from both Baselines in serum and plasma biomarkers associated with LPAR1 pathway, inflammation and/or fibrosis at Week 52.
21. Change from both Baselines in swollen and tender joint count, digital ulcer assessment and joint contracture assessment at Week 52.
Safety and Tolerability Endpoints
1.Incidence of TEAEs and the AESI (orthostatic hypotension).
2.Concomitant medication use.
3.Change from both Baselines in vital signs.
4.Change from both Baselines in 12-lead ECG measurements.
5.Change from both Baselines in clinical safety laboratory test results.
Pharmacokinetic Endpoint
1. Pre- and post-dose concentrations of HZN-825 and metabolite(s).

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: <= 75age old
• Gender: Both

Include criteria

1. Written informed consent.
2. Completed the double-blind Treatment Period (Week 52) in Trial HZNP-HZN-825-301; subjects 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.
3. Willing and able to comply with the prescribed treatment protocol and evaluations for the duration of the trial.

Exclude 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 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 considered of childbearing potential if they are not postmenopausal and not surgically sterile (documented bilateral salpingectomy, bilateral oophorectomy or hysterectomy). A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle-stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient. Fertile male subjects must use a condom throughout the trial and for 4 weeks after the last dose of trial drug. A man is considered fertile after puberty unless permanently sterile by bilateral orchidectomy.
4. Pregnant or lactating women.
5. Any new development with the subject'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.
6. Subjects 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.

Related Information

• Primary Sponsor: Sato Toshiyuki