E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic pulmonary sarcoidosis |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10037430 |
E.1.2 | Term | Pulmonary sarcoidosis |
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 |
The purpose of this proof of concept study is to determine whether CMK389 displays the safety and efficacy profile to support further development in chronic pulmonary sarcoidosis. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Subjects must have a body mass index (BMI) at screening within the range of 18 - 46 kg/m2. BMI = Body weight (kg) / [Height (m)]2 - Biopsy proven pulmonary sarcoidosis diagnosed > 1 year prior to screening - Scadding stage II, III or IV as determined by the most recent chest xray obtained within 12 months prior to screening or at screening (confirmed by the Investigator) - HRCT extent of fibrosis <20% (confirmed by the central imaging reader) at screening - Treatment with 5-15 mg/day prednisone (or prednisone oral equivalents) for ≥ 6 months prior to screening. - Co-medication with methotrexate or azathioprine for ≥ 6 months priorto screening (Note: hydroxychloroquine is allowed as background therapy but not required) - Able to perform reliable, reproducible pulmonary function test maneuvers per American Thoracic Society/European Respiratory Society (ATS/ERS) guidelines |
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E.4 | Principal exclusion criteria |
- Diagnosis of significant pulmonary hypertension (WHO group 5) requiring pharmacological treatment - Active cardiac sarcoidosis requiring treatment. Inactive cardiac sarcoidosis or stable cardiac sarcoidosis not requiring treatment are permissible. - A known diagnosis of neurosarcoidosis - Forced vital capacity (FVC) <50% of predicted at screening (central read) - Modified British Medical Research Council (mMRC) dyspnea scale ≥ 3 at screening - Concomitant treatment with leflunomide, cyclophosphamide, mycophenolate, infliximab, etanercept, adalimumab, golimumab, ustekinumab, roflumilast, pentoxifylline, and abatacept within 12 weeks of screening - Prior treatment with rituximab, canakinumab, anakinra, and tocilizumab - Current use of any inhaled substance, including but not limited to tobacco, marijuana products and use of electronic cigarette or vaping device, and excluding inhalers or nebulizers prescribed for pulmonary sarcoidosis - Any conditions or significant medical problems which in the opinion of the investigator and in consultation with the sponsor, immunocompromises the patient and/or places the patient at unacceptable risk for immunomodulatory therapy - Contraindication to FDG-PET scan investigations such as severe claustrophobia or uncontrolled diabetes - History or current diagnosis of ECG abnormalities not due to Cardiac Sarcoidosis and indicating significant risk of safety for patients participating in the study - Other protocol-defined inclusion/exclusion criteria may apply |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in forced vital capacity, % of predicted, between CMK389 and placebo. |
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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) |
- Composite index of pulmonary physiology and exercise capacity: Relative reduction in forced volume capacity ≥ 10% or relative reduction in forced expiratory volume in one second ≥ 10% or relative reduction of diffusion capacity ≥ 15% or relative reduction of 6-minute walk distance ≥ 50 meters. - [18F]-fluorodeoxyglucose positron emission tomography/computed tomography: Change in imaging maximum standardized uptake value and mean standardized uptake value. - Pulmonary physiology: Change in forced expiratory volume in one second and diffusion capacity for carbon monoxide. - Steroid use (mg days): Difference in steroid usage for each arm of the study. Exercise capacity: Change in 6-minute walk distance. - Pharmacokinetics of CMK389 maximum concentration (Cmax): The observed maximum plasma concentration (Cmax/end of infusion) [mass / volume]. - Pharmacokinetics of CMK389 trough concentration (Ctrough): The lowest concentration of drug (Ctrough) reached before the next dose is administered. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Baseline to Week 16 Pharmacokinetic endpoints: Day 1 through Week 28 |
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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 | No |
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 | Yes |
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
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 17 |
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 |
United States |
Czechia |
Denmark |
Germany |
Poland |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | No |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 13 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 13 |