E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Systemic sclerosis associated with interstitial lung disease |
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E.1.1.1 | Medical condition in easily understood language |
Systemic sclerosis is a disease characterized by abnormal and excess fibrosis, a hardening of tissues and organs. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025109 |
E.1.2 | Term | Lung involvement in systemic sclerosis |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
• 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 |
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E.2.2 | Secondary objectives of the trial |
• 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 MK7240/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 MK7240/PRA023 vs. placebo at Week 50 |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Skin Biopsy Substudy: to assess change in histology and protein expression Pharmacokinetic Substudy: Fully characterize PK of MK-7240/PRA023 in subjects with SSc-ILD
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E.3 | Principal 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 12 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. |
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E.4 | Principal exclusion criteria |
1.Subjects with a history of cancer within the last 5 years (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 <LLOQ are eligible. • Participants with positive HCV Abs at Screening must have further testing for HCV RNA. Participants with HCV RNA ≥LLOQ are not eligible for the study. Participants with positive HCV Abs but HCV RNA <LLOQ are eligible. Subjects with successfully treated Hepatitis C with no recurrence for ≥ 1 year are allowed. • Participants with a history of HIV infection or who have a positive Ab test are not eligible for the study. 6. Subjects with confirmed or suspected COVID-19 infection. Note: Subjects with recent confirmed or suspected COVID-19 infection may participate under the following conditions: • Subjects with COVID-19 infection confirmed by a PCR or an antigen test: - For asymptomatic subjects, randomization must be at least 10 days after the positive COVID-19 test. - For symptomatic subjects, randomization must be at least 10 days after onset of symptoms and at least 3 days after resolution of fever without the use of fever-reducing medications, and the participant must have a clinically meaningful improvement in symptoms. • Subjects with suspected COVID-19 infection: - For subjects with signs/symptoms suggestive of COVID-19 infection, a molecular (i.e., PCR) test must be performed to rule out COVID-19 infection before randomization. OR - Randomization must be at least 10 days after onset of symptoms and at least 3 days after resolution of fever without the use of fever-reducing medications, and the participant must have clinically meaningful improvement in symptoms 7. Treatment with: a.Tofacitinib, upadacitinib, baricitinib, abrocitinib, or filgotinib within 4 weeks of randomization b.D-penicillamine, sulfasalazine, cyclosporine, or pirfenidone within 8 weeks of randomization c.Cyclophosphamide, tocilizumab, abatacept, leflunomide, tacrolimus, or any other approved biologics for rheumatic diseases within 3 months of randomization d.Intravenous immunoglobulin within 5 months of randomization e.Rituximab within 6 months of randomization. 8. Prior exposure to MK-7240/PRA023 or other TL1A antagonists. |
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E.5 End points |
E.5.1 | 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 in mL of MK-7240/PRA023 vs. placebo over 50 weeks |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
To compare the change from Baseline in FVC in mL of MK-7240/PRA023 vs. placebo at Week 50 • To compare the change from Baseline in HRCT QILD-WL of MK7240/PRA023 vs. placebo at Week 50 • To compare proportion of subjects with an improvement in the revised CRISS score of MK-7240/PRA023 vs. placebo at Week 50 • To assess the change from Baseline in HAQ-DI of MK-7240/PRA023 vs. placebo at Week 50 • 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 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 45 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Switzerland |
Australia |
Canada |
Israel |
United Kingdom |
United States |
Belgium |
France |
Germany |
Hungary |
Italy |
Netherlands |
Norway |
Poland |
Spain |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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EoT participation in a Member State of the EU is defined as the time at which it is deemed that a sufficient number of subjects have been recruited and completed the study as stated in the regulatory application (i.e., clinical trial application) and ethics application in the Member State. Poor recruitment (recruiting less than the anticipated number in the CTA) by a Member State is not a reason for premature termination but is considered a normal conclusion to the study in that Member State |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 7 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 16 |