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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Horizon Therapeutics Ireland Designated Activity Company

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

24 Feb 2023 → 24 Feb 2025

Decision date (initial)

2024-10-20

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Horizon Therapeutics USA, Inc

External identifiers

EU CT number

2023-509783-23-00

EudraCT number

2021-006271-42

ClinicalTrials.gov

NCT04781543

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Therapy, Pharmacogenetic, Efficacy, Others

The overall objective is to investigate the efficacy, safety and tolerability
of HZN-825, a selective antagonist of LPAR1, administered BID to
subjects with diffuse cutaneous SSc in a 52-week open-label extension
following completion of the randomized, double-blind, 52-week clinical
trial (HZNP-HZN-825-301).

Secondary objectives 1

1. "The exploratory objectives are to evaluate the following after 52 weeks of open-label treatment with HZN-825: • Change from both Baselines in HAQ-DI; Physician Global Assessment (MDGA); Patient Global Assessment (PTGA); the Physical Effects and Physical Limitations subscales of the scleroderma skin patient-reported outcome (SSPRO-18); the mRSS; American College of RheumatologyComposite Response Index in Systemic Sclerosis (ACR-CRISS), among others as indicated in protocol section 8.2. • The PK of HZN-825 and metabolite(s) "

Conditions and MedDRA coding

Diffuse Cutaneous Systemic Sclerosis

Study design 1 period

Regulatory references

Plan to share IPD

Yes

IPD plan description

De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 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. "

Exclusion criteria 1

1. "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 HZNPHZN-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 HZNPHZN-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. "

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from both Baselines in FVC % predicted at Week 52

Secondary endpoints 1

1. "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. "

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Horizon Therapeutics Ireland Designated Activity Company

Sponsor organisation

Horizon Therapeutics Ireland Designated Activity Company

Address

70 Saint Stephen's Green

City

Dublin 2

Postcode

D02 E2X4

Country

Ireland

Scientific contact point

Organisation

Horizon Therapeutics Ireland Designated Activity Company

Contact name

Arati Kanchi

Public contact point

Organisation

Horizon Therapeutics Ireland Designated Activity Company

Contact name

Arati Kanchi

Third parties 15

Locations

9 EU/EEA countries · 47 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 55 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications