Study of Efficacy, Safety and Tolerability of CMK389 in Patients With Chronic Pulmonary Sarcoidosis

Study Overview
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Brief Summary
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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.

Official Title
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A Subject and Investigator Blinded, Randomized, Placebo-controlled, Repeat-dose, Multicenter Study to Investigate Efficacy, Safety, and Tolerability of CMK389 in Patients With Chronic Pulmonary Sarcoidosis

Conditions
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Pulmonary Sarcoidosis

Intervention / Treatment
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* Drug: CMK389
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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 x-ray 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 prior to 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 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 A diagnosis of Lofgren's syndrome A history of pancreatitis Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will be assigned to one of two treatment arms, either CMK389 or placebo.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CMK389<br>CMK389 | Drug: CMK389<br>* single i.v. dose every 4 weeks<br>|
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br>* single i.v. dose every 4 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Forced Vital Capacity | Change in forced vital capacity, % of predicted, between CMK389 and placebo. | Baseline to Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline to Week 16 | 
| [18F]-fluorodeoxyglucose positron emission tomography/computed tomography | Change in imaging maximum standardized uptake value and mean standardized uptake value. | Baseline to Week 16 | 
| Pulmonary physiology | Change in forced expiratory volume in one second and diffusion capacity for carbon monoxide. | Baseline to Week 16 | 
| Steroid use (mg days) | Difference in steroid usage for each arm of the study. | Baseline to Week 16 | 
| Exercise capacity | Change in 6-minute walk distance. | Baseline to Week 16 | 
| Pharmacokinetics of CMK389 maximum concentration (Cmax) | The observed maximum plasma concentration (Cmax/end of infusion) [mass / volume]. | Day 1 through Week 28 | 
| Pharmacokinetics of CMK389 trough concentration (Ctrough) | The lowest concentration of drug (Ctrough) reached before the next dose is administered. | Day 1 through Week 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chronic pulmonary sarcoidosis