Clinical trial NCT04064242: Study of Efficacy, Safety and Tolerability of CMK389 in Patients With Chronic Pulmonary Sarcoidosis
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pulmonary Sarcoidosis
Keywords: chronic pulmonary sarcoidosis
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2019-08-21
Enrollment: 62
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be assigned to one of two treatment arms, either CMK389 or placebo.
Primary purpose: TREATMENT

Brief 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.

Detailed 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

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

Primary outcomes:
measure: Change in Percent Predicted FVC From Baseline to 16 Weeks of Treatment
timeFrame: Baseline, Week 16
Secondary outcomes:
measure: Number of Participants Who Had an Increase in Steroid Usage From Baseline to 16 Weeks of Treatment
timeFrame: Baseline, Week 16
measure: Number of Participants Who Deteriorate From Baseline to 16 Weeks of Treatment
timeFrame: Baseline, Week 16
measure: Percent Change in [18F]-FDG-PET/CT (SUVmax and SUVmean) From Baseline to 16 Weeks of Treatment
timeFrame: Baseline, Week 16
measure: The Observed Serum Concentration Following CMK389 Administration at End of Infusion
timeFrame: Post 1 hour: Day 1, Day 29, Day 57, Day 85
measure: Pre-dose Trough Concentration (Ctrough) of CMK389
timeFrame: Pre-dose: Day 1, Day 29, Day 57, Day 85
measure: Change in FEV1 From Baseline to 16 Weeks of Treatment
timeFrame: Baseline, Week 16
measure: Change in Diffusion Capacity of the Lung for Carbon Monoxide (DLCO) From Baseline to 16 Weeks of Treatment
timeFrame: Baseline, Week 16
measure: Change in 6-minute Walk Distance (6MWD) From Baseline to 16 Weeks of Treatment
timeFrame: Baseline, Week 16
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Novartis Investigative Site
state: Alabama
city: Gainesville
country: United States
facility: Univ of Florida College of Medicine x
state: Florida
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Baltimore
country: United States
facility: John Hopkins Asthma And Alrgy Cntr
state: Maryland
city: New York
country: United States
facility: Icahn School Of Med At Mount Sinai .
state: New York
city: Greenville
country: United States
facility: East Carolina University .
state: North Carolina
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Brno
country: Czechia
facility: Novartis Investigative Site
city: Olomouc
country: Czechia
facility: Novartis Investigative Site
city: Aarhus N
country: Denmark
facility: Novartis Investigative Site
city: Hellerup
country: Denmark
facility: Novartis Investigative Site
city: Odense C
country: Denmark
facility: Novartis Investigative Site
city: Heidelberg
country: Germany
facility: Novartis Investigative Site
state: Baden Wurttemberg
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Frankfurt
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Hannover
country: Germany
facility: Novartis Investigative Site
city: Bialystok
country: Poland
facility: Novartis Investigative Site
city: Lodz
country: Poland
facility: Novartis Investigative Site
city: Warszawa
country: Poland
facility: Novartis Investigative Site
city: Edinburgh
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
References: