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

Pulmonary Sarcoidosis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04064242
• Other study ID #: CCMK389X2201
• Status: Completed
• Phase: Phase 2
• Start date: September 23, 2020
• Est. completion date: December 12, 2023

Study information

• Verified date: February 2024
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 62
• Est. completion date: December 12, 2023
• Est. primary completion date: September 19, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Pulmonary Sarcoidosis
• Sarcoidosis
• Sarcoidosis, Pulmonary

Intervention

Drug:
• CMK389
single i.v. dose every 4 weeks
• Placebo
single i.v. dose every 4 weeks

Locations

Country	Name	City	State
Czechia	Novartis Investigative Site	Brno Bohunice
Czechia	Novartis Investigative Site	Olomouc
Denmark	Novartis Investigative Site	Aarhus N
Denmark	Novartis Investigative Site	Hellerup
Denmark	Novartis Investigative Site	Odense C
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Frankfurt
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hannover
Germany	Novartis Investigative Site	Heidelberg	Baden-Württemberg
Poland	Novartis Investigative Site	Bialystok
Poland	Novartis Investigative Site	Lodz
Poland	Novartis Investigative Site	Warszawa
United Kingdom	Novartis Investigative Site	Edinburgh
United Kingdom	Novartis Investigative Site	London
United States	John Hopkins Asthma and Allergy Center	Baltimore	Maryland
United States	Univ of Alabama at Birmingham .	Birmingham	Alabama
United States	Univ of Florida College of Medicine x	Gainesville	Florida
United States	East Carolina University .	Greenville	North Carolina
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Icahn School Of Med At Mount Sinai .	New York	New York
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Czechia,  Denmark,  Germany,  Poland,  United Kingdom, 

Outcome

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