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

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

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.

Study Overview

• Status: Completed
• Conditions: Pulmonary Sarcoidosis
• Intervention / Treatment: Drug: CMK389; Drug: Placebo

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

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Phase 2

Contacts and Locations

Study Locations

• Czechia
  • Brno, Czechia, 625 00
    • Novartis Investigative Site
  • Olomouc, Czechia, 779 00
    • Novartis Investigative Site
• Denmark
  • Aarhus N, Denmark, 8200
    • Novartis Investigative Site
  • Hellerup, Denmark, 2900
    • Novartis Investigative Site
  • Odense C, Denmark, DK 5000
    • Novartis Investigative Site
• Germany
  • Essen, Germany, 45147
    • Novartis Investigative Site
  • Frankfurt, Germany, 60596
    • Novartis Investigative Site
  • Hamburg, Germany, 20246
    • Novartis Investigative Site
  • Hannover, Germany, 30625
    • Novartis Investigative Site
  • Baden Wurttemberg
    • Heidelberg, Baden Wurttemberg, Germany, 69126
      • Novartis Investigative Site
• Poland
  • Bialystok, Poland, 15-044
    • Novartis Investigative Site
  • Lodz, Poland, 90 153
    • Novartis Investigative Site
  • Warszawa, Poland, 01-138
    • Novartis Investigative Site
• United Kingdom
  • Edinburgh, United Kingdom, EH1 1BE
    • Novartis Investigative Site
  • London, United Kingdom, SW3 6PH
    • Novartis Investigative Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294-3300
      • Novartis Investigative Site
  • Florida
    • Gainesville, Florida, United States, 32610
      • Univ of Florida College of Medicine x
  • Kansas
    • Kansas City, Kansas, United States, 66160-7330
      • University of Kansas Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • John Hopkins Asthma And Alrgy Cntr
  • New York
    • New York, New York, United States, 10029
      • Icahn School Of Med At Mount Sinai .
  • North Carolina
    • Greenville, North Carolina, United States, 27858
      • East Carolina University .
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CMK389; CMK389 10 mg/kg i.v. every 4 weeks for a total of 4 doses	Drug: CMK389; single i.v. dose every 4 weeks
Placebo Comparator: Placebo; Placebo i.v. every 4 weeks for a total of 4 doses	Drug: Placebo; single i.v. dose every 4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Percent Predicted FVC From Baseline to 16 Weeks of Treatment	To assess the effect of CMK389 compared to placebo after 16 weeks of treatment on spirometry (Forced Vital Capacity). Forced Vital Capacity (FVC) is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. Percent predicted FVC is the percentage of the age, height and gender adjusted predicted value.	Baseline, Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Had an Increase in Steroid Usage From Baseline to 16 Weeks of Treatment	The Clinical Status Evaluation (CSE) served as a safety evaluation and served to establish the patient's clinical status (Clinical Status Determination [CSD]). CSE was performed prior to the titration of steroids, and the CSD guided selection of the next dose of steroids. Participants with CSD of "improved" or "stable" decreased steroid dose by 1 step on the dosing scale. Participants with CSD of "deteriorating" were ineligible to continue the study (if found during the run-in epoch or at study Day 1); or they increased steroid dose by 1 step (if found during the treatment epoch).	Baseline, Week 16
Number of Participants Who Deteriorate From Baseline to 16 Weeks of Treatment	Composite index of pulmonary physiology (CIPP) and exercise capacity: a participant who deteriorated from baseline to each visit was defined as a patient with: relative reduction if FVC ≥ 10%, or relative reduction if FEV1 ≥ 10%, or relative reduction of DLCO ≥ 15%, or relative reduction of 6MWD ≥ 50 m.	Baseline, Week 16
Percent Change in [18F]-FDG-PET/CT (SUVmax and SUVmean) From Baseline to 16 Weeks of Treatment	[18F]-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) maximum standardized uptake value and mean standardized uptake value (SUVmax and SUVmean) imaging was used to assess potential anti-inflammatory effects by CMK389 on the sarcoidosis process. All participants underwent whole-body head to mid-thigh [18F]FDG-PET/CT imaging state-of-the-art, 3D PET/CT scanners with a reconstructed resolution of ≤5 mm.	Baseline, Week 16
The Observed Serum Concentration Following CMK389 Administration at End of Infusion	Pharmacokinetic parameters were directly derived from the PK concentration data using non-compartmental analysis.	Post 1 hour: Day 1, Day 29, Day 57, Day 85
Pre-dose Trough Concentration (Ctrough) of CMK389	Pharmacokinetic parameters were directly derived from the PK concentration data using non-compartmental analysis. Ctrough is the observed plasma concentration that is just prior to the beginning of a dosing interval.	Pre-dose: Day 1, Day 29, Day 57, Day 85
Change in FEV1 From Baseline to 16 Weeks of Treatment	FEV1 (forced expiratory volume in one second) is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation, measured through spirometry testing. The least-squares means for change from baseline in FEV1 to assess the effect of CMK389 compared to placebo after 16 weeks were obtained from a mixed effects model for repeated measures (MMRM). A positive change from baseline in pre-dose FEV1 is considered a favourable outcome.	Baseline, Week 16
Change in Diffusion Capacity of the Lung for Carbon Monoxide (DLCO) From Baseline to 16 Weeks of Treatment	DLCO is a measurement to assess the lungs' ability to transfer gas from inspired air to the bloodstream. The least squares means for change from baseline in DLCO to assess the effect of CMK389 compared to placebo after 16 weeks were obtained from a mixed effects model for repeated measures (MMRM). A positive change from baseline in DLCO is considered a favourable outcome.	Baseline, Week 16
Change in 6-minute Walk Distance (6MWD) From Baseline to 16 Weeks of Treatment	The 6MWD test is self-paced, with standardized instructions and encouragement being given as participants walk as far as possible over 6 minutes through a flat corridor. The final distance is recorded in meters. The least squares means for change from baseline in 6MWD to assess the effect of CMK389 compared to placebo after 16 weeks were obtained from a mixed effects model for repeated measures (MMRM). A positive change from baseline in 6MWD is considered a favourable outcome.	Baseline, Week 16

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• A Plain Language Trial Summary is available on www.novctrd.com

Study record dates

Study Major Dates

• Study Start (Actual): September 23, 2020
• Primary Completion (Actual): September 19, 2023
• Study Completion (Actual): December 12, 2023

Study Registration Dates

• First Submitted: August 20, 2019
• First Submitted That Met QC Criteria: August 20, 2019
• First Posted (Actual): August 21, 2019

Study Record Updates

• Last Update Posted (Actual): April 13, 2025
• Last Update Submitted That Met QC Criteria: April 10, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: chronic pulmonary sarcoidosis
• Additional Relevant MeSH Terms: Immune System Diseases; Respiratory Tract Diseases; Lung Diseases; Hypersensitivity; Lymphatic Diseases; Lymphoproliferative Disorders; Lung Diseases, Interstitial; Hypersensitivity, Delayed; Sarcoidosis, Pulmonary; Sarcoidosis
• Other Study ID Numbers: CCMK389X2201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No