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 is 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

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

Contacts and Locations

• Study Contact: Name: Novartis Pharmaceuticals; Phone Number: 1-888-669-6682; Email: novartis.email@novartis.com
• Study Contact Backup: Name: Novartis Pharmaceuticals; Phone Number: +41613241111

Study Locations

• Czechia
  • Brno Bohunice, 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-Württemberg
    • Heidelberg, Baden-Württemberg, 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
      • Univ of Alabama at Birmingham .
  • 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 Allergy Center
  • 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

Other protocol-defined inclusion/exclusion criteria may apply

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
Placebo Comparator: Placebo	Drug: Placebo; single i.v. dose every 4 weeks
Experimental: CMK389	Drug: CMK389; single i.v. dose every 4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Forced Vital Capacity	Change in forced vital capacity, % of predicted, between CMK389 and placebo.	Baseline to Week 16

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

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 (Estimated): February 21, 2024
• Last Update Submitted That Met QC Criteria: February 20, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: chronic pulmonary sarcoidosis
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Lung Diseases; Hypersensitivity; 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