A study of MK-7240/PRA023 in patients with Systemic Sclerosis Associated with Interstitial Lung Disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Prometheus Biosciences Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

29 Apr 2022 → ongoing

Decision date (initial)

2024-07-17

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Prometheus Biosciences Inc.

External identifiers

EU CT number

2023-509743-27-00

EudraCT number

2021-005206-10

WHO UTN

U1111-1309-6150

ClinicalTrials.gov

NCT05270668

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Pharmacogenetic, Efficacy, Safety, Pharmacokinetic, Therapy

• To assess the safety and tolerability of MK-7240/PRA023 in SSc-ILD
• To compare the annual rate of change from Baseline in forced vital capacity (FVC) in mL of MK-7240/PRA023 vs. placebo over 50 weeks

Secondary objectives 1

1. • To compare the change from Baseline in FVC in mL of MK7240/PRA023 vs. placebo at Week 50 • To compare the change from Baseline in high-resolution computer tomography (HRCT) quantitative interstitial lung disease – whole lung (QILD-WL) of MK-7240/PRA023 vs. placebo at Week 50 • To compare proportion of subjects with an improvement in the revised Composite Response Index in Systemic Sclerosis (CRISS) score of MK-7240/PRA023 vs. placebo at Week 50 • To assess the change from Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) of MK-7240/PRA023 vs. placebo at Week 50 • To assess the change from Baseline in Living with Pulmonary Fibrosis (L-PF) patient-reported quality of life (QoL) outcome of MK-7240/PRA023 vs. placebo at Week 50

Conditions and MedDRA coding

Systemic sclerosis associated with interstitial lung disease

Study design 4 periods

Regulatory references

Plan to share IPD

Yes

IPD plan description

Plan to share IPD that underline results in publication

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 2

1. 1.Male or female ≥ 18 years of age. 2.Subjects must meet the 2013 ACR/EULAR definition of SSc. 3.Subjects must have had SSc onset (defined by first non-Raynaud symptom) ≤ 5 years (60 months) prior to screening. 4.Subjects must have diffuse cutaneous scleroderma defined as any level of skin thickening proximal to the elbows and knees exclusive of the face and neck. Total mRSS must be 10 to 35 units, inclusive. 5.Subjects must have SSc-related ILD of fibrotic disease in lung confirmed by HRCT ≥ 10% extent of involvement, assessed by central reading. 6.FVC ≥ 45% of predicted normal. 7.Diffusing capacity of lung for carbon monoxide (DLCO) ≥ 45% of predicted normal (corrected for hemoglobin [Hgb]). 8.Meet at least one of the following criteria: a. C-reactive protein (CRP) > upper limit of normal (ULN) b. Erythrocyte sedimentation rate (ESR) > 28 mm/hr c. Positive for anti-topoisomerase (anti-Scl-70) antibody 9.Background therapy is not required, but subjects receiving background therapy must meet drug stabilization requirements, as applicable: a.Either mycophenolate mofetil (not to exceed 3 g/day) or oral or subcutaneous methotrexate (not to exceed 25 mg/week) or azathioprine (not to exceed 150 mg/day) for ≥ 4 months prior to randomization (not more than 1 therapy) and on a stable dose for 4 weeks prior to randomization b.Subjects who have been on nintedanib for ≥ 6 months (and stable dose for at least 4 weeks) prior to randomization may enter the study provided that there has not been any improvement in FVC (% and absolute) from prior to the initiation of nintedanib therapy c.A stable dose of oral corticosteroids (≤ 10 mg/day prednisone equivalent) for 2 weeks prior to randomization. Inhaled and topical corticosteroids are permitted.
2. 10.A female subject is eligible to participate if not pregnant or breastfeeding, and at least one of the following conditions applies: • Is not a woman of childbearing potential (WOCBP) OR • Is a WOCBP and: - Uses an acceptable contraceptive method, or is abstinent from penilevaginal intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis),from at least 4 weeks prior to Day 1/Week 0, during the intervention period, and for at least 14 weeks after the last dose of study intervention. The Investigator should evaluate the potential for contraceptive method failure (i.e., noncompliance, recently initiated) in relationship to the first dose of study intervention. Contraceptive use by WOCBP should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. For any background medications, the local label should be followed for contraception. - Has a negative highly sensitive pregnancy test (urine or serum) as required by local regulations within 24 hours (for a urine test) or 72 hours (for a serum test) before the first dose of study intervention. If a urine test cannot be confirmed as negative (e.g., an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive. - Medical history, menstrual history, and recent sexual activity has been reviewed by the investigator to decrease the risk for inclusion of a WOCBP with an early undetected pregnancy 11.Able to provide written informed consent and understand and comply with the requirements of the study.

Exclusion criteria 1

1. 1.Subjects with a history of cancer within the last 5 years (other than (other than non-melanoma skin cell cancers cured by local resection or cervical carcinoma in situ).Existing non-melanoma skin cell cancers must be removed prior to enrollment. Subjects with carcinoma in situ or localized cervical cancer, treated with definitive surgical intervention, are allowed. 2. Subject has active TB or meets TB exclusionary parameters 3.Subjects with chronic or recurrent infection (such as chronic pyelonephritis, osteomyelitis, and bronchiectasis). 4. Subjects with any active infections (excluding fungal infections of nail beds) including, but not limited to, those that require IV or IM antimicrobial treatment 4 weeks or oral antimicrobial treatment 2 weeks prior to randomization. 5.Subjects known to be infected with HBV, HCV, or HIV • Participants with positive HBsAg are excluded from the study. Participants with negative HBsAg and positive HBcAb must have further testing for HBV-DNA. Participants with HBV-DNA ≥LLOQ are not eligible for the study. Participants with HBV-DNA

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 1.The proportion of subjects reporting adverse events (AEs), serious adverse events (SAEs), AEs leading to discontinuation, and markedly abnormal laboratory values. 2.To compare the annual rate of change from Baseline in FVC in mL of MK-7240/PRA023 vs. placebo over 50 weeks

Secondary endpoints 3

1. 1.To compare the change from Baseline in FVC in mL of MK-7240/PRA023 vs. placebo at Week 50. 2.To compare the change from Baseline in HRCT QILD-WL of MK-7240/PRA023 vs. placebo at Week 50
2. 3.To compare proportion of subjects with an improvement in the revised CRISS score of MK-7240/PRA023 vs. placebo at Week 50. 4.To assess the change from Baseline in HAQ-DI of MK-7240/PRA023 vs. placebo at Week 50
3. To assess the change from Baseline in L-PF patient-reported quality of life (QoL) outcome of MK-7240/PRA023 vs. placebo at Week 50

Investigational products

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

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Prometheus Biosciences Inc.

Sponsor organisation

Prometheus Biosciences Inc.

Address

3050 Science Park Road

City

San Diego

Postcode

92121-1102

Country

United States

Scientific contact point

Organisation

Prometheus Biosciences Inc.

Contact name

Sonia Villegas

Public contact point

Organisation

Prometheus Biosciences Inc.

Contact name

Clinical Operations

Third parties 8

Locations

8 EU/EEA countries · 36 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

Documents 130 files

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

Application history

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