Tulisokibart in Systemic Sclerosis-Associated Interstitial Lung Disease: A Randomized, Placebo-Controlled Trial of Safety and Efficacy
- Trial ID
- 2023-509743-27-00
- Protocol
- PR200-104_MK-7240-00
- Sponsor
- Prometheus Biosciences Inc.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the efficacy and safety of MK-7240/PRA023 in subjects with systemic sclerosis associated with interstitial lung disease. Clinical relevance is established by comparing the annual rate of change from baseline in forced vital capacity (FVC) in mL between the MK-7240/PRA023 group and the placebo group over 50 weeks. Secondary objectives include:
- Comparison of the change from baseline in FVC in mL at week 50.
- Comparison of the change from baseline in high-resolution computed tomography (HRCT) quantitative interstitial lung disease – whole lung (QILD-WL) at week 50.
- Comparison of the proportion of subjects demonstrating improvement in the revised Composite Response Index in Systemic Sclerosis (CRISS) score at week 50.
- Assessment of the change from baseline in the Health Assessment Questionnaire Disability Index (HAQ-DI) at week 50.
- Assessment of the change from baseline in the Living with Pulmonary Fibrosis (L-PF) patient-reported quality of life outcome at week 50.
Participants
This clinical trial involves 49 participants diagnosed with systemic sclerosis associated with interstitial lung disease. The study population includes both male and female adults. The primary objectives are:
- To assess the safety and tolerability of MK-7240/PRA023.
- To compare the annual rate of change from baseline in forced vital capacity (FVC) in mL of MK-7240/PRA023 versus a placebo over 50 weeks.
Plans and Procedures
This Phase II, double-blind, randomized, placebo-controlled study is designed to evaluate the efficacy and safety of tulisokibart in subjects with systemic sclerosis associated with interstitial lung disease. The primary objective is to compare the annual rate of change from baseline in forced vital capacity (FVC) against a placebo consisting of 0.9% normal saline over a 50-week period. The study will also assess the safety and tolerability of the investigational product. The trial involves an initial screening visit to confirm eligibility based on specific clinical, laboratory, and imaging criteria, such as high-resolution computed tomography (HRCT) findings. Following screening, participants will receive the study intervention via intravenous use. The overall study duration for evaluating efficacy includes a 50-week treatment period. Early termination from the study may occur due to adverse events or other clinical requirements defined by the protocol.
Treatment
The experimental medication is tulisokibart, provided as a concentrate for solution for infusion. The administration consists of a 1000 mg dose via intravenous use.
The placebo consists of 0.9% normal saline. This comparator is presented as a solution for infusion and is designed to be identical to the investigational medicinal product in appearance and pharmaceutical form.
Efficacy
The efficacy of the investigational product will be evaluated in subjects with systemic sclerosis associated with interstitial lung disease. The primary efficacy endpoint is the comparison of the annual rate of change from baseline in forced vital capacity (FVC) in mL between the study group and the placebo group over 50 weeks.
Secondary efficacy assessments at week 50 include:
- Comparison of the change from baseline in FVC in mL.
- Comparison of the change from baseline in high-resolution computed tomography (HRCT) quantitative interstitial lung disease-weighted lesion (QILD-WL).
- Comparison of the proportion of subjects showing improvement in the revised Cutaneous Scleroderma Interstitial Lung Disease Score (CRISS).
- Assessment of the change from baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI).
- Assessment of the change from baseline in the Leicester Pulmonary Function questionnaire (L-PF) patient-reported outcome (PRO) for quality of life (QoL).
Inclusion and Exclusion Criteria
Inclusion Criteria
- 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.
- 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.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
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Belgium | Not Recruiting | 20 Sept 2022 | 4 |
 France | Not Recruiting | 20 Sept 2022 | 3 |
 Germany | Not Recruiting | 20 Sept 2022 | 4 |
 Hungary | Not Recruiting | 20 Sept 2022 | 9 |
 Italy | Not Recruiting | 20 Sept 2022 | 13 |
 The Netherlands | Not Recruiting | 20 Sept 2022 | — |
 Poland | Not Recruiting | 20 Sept 2022 | 53 |
 Spain | Not Recruiting | 20 Sept 2022 | 16 |
| Netherlands | — | — | 1 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
tulisokibart | Test | CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS USE | 1000 | 52 | PRD11039284 |
tulisokibart | Test | CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS USE | 1000 | 52 | PRD10740872 |
Placebo is 0.9% normal saline. It is identical to IMP and its pharmaceutical form is solution for infusion. | Placebo | N/A | — | — | — | N/A |