Systemic sclerosis associated with interstitial lung disease MedDRA version: 21.0 Level: LLT Classification code 10025109 Term: Lung involvement in systemic sclerosis System Organ Class: 100000004855
Conditions
Interventions
Product Code: MK-7240/PRA023
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: tulisokibart
CAS Number: 2648504-55-4
Current Sponsor code: MK-7240/PRA023
Other descript
Sponsors
Prometheus Biosciences, Inc., a subsidiary of Merck & Co., Inc.
Eligibility
Sex/Gender
All
Inclusion 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 15 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.CRP > upper limit of normal (ULN) b.Erythrocyte sedimentation rate (ESR) > 28 mm/hr c.Positive for anti-topoisomerase (anti-Scl-70) antibody 9.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.For subjects who are women of childbearing potential (WOCBP) involved in any sexual intercourse that could lead to pregnancy, the subject has used two highly effective methods of contraception for at least 4 weeks prior to Day 1 and agrees to continue to use two highly effective methods of contraception until at least 12 weeks after the last dose of study drug. 11.Male subjects and/or their partners must use two highly effective methods of contraception from screening to 12 weeks after the last dose of study drug. 12.Male subjects must refrain from sperm donation or banking from randomization to 12 weeks after the last dose of study drug. 13.Able to provide written informed consent and understand and comply with the requirements of the study. 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 80 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: 1.WOCBP and men with female partners of childbearing potential who are unwilling or unable to use two highly effective methods of contraception to avoid pregnancy for the entire study period and for up to 12 weeks after the last dose of study drug. 2.Women who are pregnant or breastfeeding. 3.Women with a positive pregnancy test on enrollment or prior to randomization. 4.Airway obstruction (pre-bronchodilator Forced Expiratory Volume in 1 second (FEV1)/FVC < 0.65). 5.Clinically significant pulmonary arterial hypertension (PAH) on right heart catheterization and requiring 2 oral or inhaled therapies or 1 parenteral therapy. 6.Other clinically significant pulmonary abnormalities. 7.History of autologous stem cell or lung transplantation. 8.Positive for serum anti-centromere antibody. 9.Current clinical diagnosis of another inflammatory connective tissue disease (e.g., systemic lupus erythematosus, rheumatoid arthritis, mixed connective tissue disease, or dermato/polymyositis). Concomitant scleroderma-associated myopathy, fibromyalgia, and secondary Sjögren's are allowed. 10.Subjects who are scheduled or anticipate the need for surgery, aside from dermatologic procedures. 11.Subjects who have a history of clinically significant drug or alcohol abuse. 12.Subjects who are current smoker (including e-cigarettes) / smoking within 6 months of screening. 13.Current symptoms of severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal (including severe recurrent aspiration), cardiac, neurological, ophthalmologic, or cerebral disease. Concomitant medical conditions that in the opinion of the Investigator might place the subject at unacceptable risk for participation in this study. 14.Subjects with a history of cancer within the last 5 years (other than non-melanoma skin cell cancers cured by local resection or cervical 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. 15.Subjects at risk for tuberculosis (TB). Specifically, subjects with: a.A history of active TB which was not successfully treated with completion of treatment b.Current clinical, radiographic, or laboratory evidence of active TB c.Latent TB which was not successfully treated. Subjects with a positive TB screening test indicative of latent TB will not be eligible for the study unless active TB infection has been ruled out, and an appropriate course of intervention for latent TB has been initiated at least 2 weeks prior to randomization, and no evidence of active TB during screening. 16.Subjects with any serious infection within the last 3 months, or any chronic bacterial infection (such as chronic pyelonephritis, osteomyelitis, and bronchiectasis). 17.Female subjects who have had a breast cancer screening that is suspicious for malignancy, and in whom the possibility of malignancy cannot be reasonably excluded following additional clinical, laboratory, or other diagnostic evaluations. 18.Subjects with any active infections (excluding fungal infections of nail beds) including, but not limited to, those that require IV antimicrobial treatment 4 weeks or oral antimicrobial treatment 2 weeks prior to randomization. Subjects with evidence of Human Immunodeficiency Virus (HIV), Hepatitis B, or Hepatitis C infection detected during screening are also excluded, but subjects with successfully treated Hepat
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To assess the safety and tolerability of PRA023 in SSc-ILD • To compare the annual rate of change from Baseline in forced vital capacity (FVC), of PRA023 vs. placebo over 50 weeks;Secondary Objective: • To compare the change from Baseline in FVC at Week 50 • To compare the change from Baseline in high-resolution computer tomography (HRCT) at Week 50 • To compare the annual rate of change in percent predicted FVC • To compare proportion of subjects with an improvement in the American College of Rheumatology Combined Response Index in Systemic Sclerosis (ACR CRISS) score at Week 50;Primary end point(s): _ The proportion of subjects reporting adverse events (AEs), serious adverse events (SAEs), AEs leading to discontinuation, and markedly abnormal laboratory values _ To compare the annual rate of change from Baseline in FVC;Timepoint(s) of evaluation of this end point: Week 50 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): _To compare the change from Baseline in FVC _To compare the annual rate of change in percent predicted FVC _To compare the change from Baseline in HRCT _To compare proportion of subjects with an improvement of the ACR CRISS score;Timepoint(s) of evaluation of this end point: Week 50 | — |
Countries
Australia, Belgium, Canada, France, Germany, Hungary, Israel, Italy, Netherlands, Norway, Poland, Spain, Switzerland, United Kingdom, United States
Contacts
Public ContactClinical Operations
Prometheus Biosciences, Inc., a subsidiary of Merck & Co., Inc.
Outcome results
None listed