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

Novartis

Status and phase: Completed; Phase 2

Conditions: Pulmonary Sarcoidosis

Treatments: Drug: Placebo; Drug: CMK389

Study type: Interventional

Funder types: Industry

Identifiers

NCT04064242

CCMK389X2201

Details and patient eligibility

About

The purpose of this proof of concept study was to determine whether CMK389 displays the safety and efficacy profile to support further development in chronic pulmonary sarcoidosis.

Full description

This was a subject and investigator blinded, randomized, placebo-controlled, parallel-group, repeat-dose, multicenter, non-confirmatory study of CMK389 in chronic pulmonary sarcoidosis. This study investigated the safety and efficacy of 10 mg/kg CMK389 administered intravenously (i.v.) every 4 weeks for a total of 4 doses, versus placebo

Enrollment: 62 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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62 participants in 2 patient groups, including a placebo group

CMK389

Experimental group

Description:

CMK389 10 mg/kg i.v. every 4 weeks for a total of 4 doses

Treatment:

Drug: CMK389

Placebo

Placebo Comparator group

Description:

Placebo i.v. every 4 weeks for a total of 4 doses

Treatment:

Drug: Placebo