Phase 2 N=62 Randomized Quadruple-blind Treatment

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

Pulmonary Sarcoidosis

Bottom Line

View on ClinicalTrials.gov: NCT04064242 ↗

Enrolled (actual)

Serious AEs

3.2%

Results posted

Oct 2024

Primary outcome: Primary: Change in Percent Predicted FVC From Baseline to 16 Weeks of Treatment — -0.48; 1.02 Percent predicted — p=0.1804

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: CMK389 (Drug); Placebo (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: Novartis Pharmaceuticals
Primary completion: Sep 2023

Outcome Measures

Outcome	Result	p-value
PRIMARY Change in Percent Predicted FVC From Baseline to 16 Weeks of Treatment	-0.48; 1.02	0.1804
SECONDARY Number of Participants Who Had an Increase in Steroid Usage From Baseline to 16 Weeks of Treatment	5; 4	—
SECONDARY Number of Participants Who Deteriorate From Baseline to 16 Weeks of Treatment	9; 10	—
SECONDARY Percent Change in [18F]-FDG-PET/CT (SUVmax and SUVmean) From Baseline to 16 Weeks of Treatment	-29.23; 26.78; -23.40; -16.48; -12.89; -19.07	—
SECONDARY The Observed Serum Concentration Following CMK389 Administration at End of Infusion	453000; 533000; 571000; 541000	—
SECONDARY Pre-dose Trough Concentration (Ctrough) of CMK389	0.00; 83500; 105000; 125000	—
SECONDARY Change in FEV1 From Baseline to 16 Weeks of Treatment	-0.03; 0.00	0.783
SECONDARY Change in Diffusion Capacity of the Lung for Carbon Monoxide (DLCO) From Baseline to 16 Weeks of Treatment	-0.58; -0.40	0.608
SECONDARY Change in 6-minute Walk Distance (6MWD) From Baseline to 16 Weeks of Treatment	11.21; 10.50	0.479

Summary

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.

Eligibility Criteria

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

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT04064242). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.