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Completed

NCT Number: NCT04064242

Study of 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.

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Key information

Conditions

Pulmonary Sarcoidosis Hemic and Lymphatic Diseases Hypersensitivity Hypersensitivity, Delayed Immune System Diseases Lung Diseases Lung Diseases, Interstitial Lymphatic Diseases Lymphoproliferative Disorders Respiratory Tract Diseases Sarcoidosis Sarcoidosis, Pulmonary

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Novartis Investigative Site, Brno, Czechia

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About this study

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

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

CMK389

Drug

single i.v. dose every 4 weeks

Placebo

Drug

single i.v. dose every 4 weeks

Primary outcomes

  1. Change in Percent Predicted FVC From Baseline to 16 Weeks of Treatment

    Time frame: Baseline, Week 16

    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.

Secondary outcomes

  1. Number of Participants Who Had an Increase in Steroid Usage From Baseline to 16 Weeks of Treatment

    Time frame: Baseline, Week 16

    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).

  2. Number of Participants Who Deteriorate From Baseline to 16 Weeks of Treatment

    Time frame: Baseline, Week 16

    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.

  3. Percent Change in [18F]-FDG-PET/CT (SUVmax and SUVmean) From Baseline to 16 Weeks of Treatment

    Time frame: Baseline, Week 16

    [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.

  4. The Observed Serum Concentration Following CMK389 Administration at End of Infusion

    Time frame: Post 1 hour: Day 1, Day 29, Day 57, Day 85

    Pharmacokinetic parameters were directly derived from the PK concentration data using non-compartmental analysis.

  5. Pre-dose Trough Concentration (Ctrough) of CMK389

    Time frame: Pre-dose: Day 1, Day 29, Day 57, Day 85

    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.

  6. Change in FEV1 From Baseline to 16 Weeks of Treatment

    Time frame: Baseline, Week 16

    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.

  7. Change in Diffusion Capacity of the Lung for Carbon Monoxide (DLCO) From Baseline to 16 Weeks of Treatment

    Time frame: Baseline, Week 16

    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.

  8. Change in 6-minute Walk Distance (6MWD) From Baseline to 16 Weeks of Treatment

    Time frame: Baseline, Week 16

    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.

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Official study 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

Important dates

Study start
2020
Primary completion
2023
Study completion
2023
First posted
Aug 21, 2019
Registry last updated
Apr 13, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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