Pulmonary SarcoidosisPhase 2NCT04064242

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

A Phase 2 study testing CMK389 in people with Pulmonary Sarcoidosis, run by Novartis Pharmaceuticals at 22 sites in 6 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 to 75 years
Conditions the study is for: Pulmonary Sarcoidosis
What is being tested?: CMK389
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 62 participants
Where: 22 sitesin 6 countries
Study dates: 23 Sep 2020to 12 Dec 2023
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Show all 13Show fewer

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

Trial locations and contacts

22 sites in 6 countries.

Country

City, postcode or hospital

22 sites in 6 countries

United States7 sites

John Hopkins Asthma And Alrgy Cntr
Baltimore, Maryland, 21224
Novartis Investigative Site
Birmingham, Alabama, 35294-3300
Univ of Florida College of Medicine x
Gainesville, Florida, 32610
East Carolina University .
Greenville, North Carolina, 27858
University of Kansas Medical Center
Kansas City, Kansas, 66160-7330
Icahn School Of Med At Mount Sinai .
New York, New York, 10029
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15213

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Germany5 sites

Novartis Investigative Site
Essen, 45147
Novartis Investigative Site
Frankfurt, 60596
Novartis Investigative Site
Hamburg, 20246
Novartis Investigative Site
Hanover, 30625
Novartis Investigative Site
Heidelberg, Baden-Wurttemberg, 69126

Other trials in Germany

Denmark3 sites

Novartis Investigative Site
Aarhus N, 8200
Novartis Investigative Site
Hellerup, 2900
Novartis Investigative Site
Odense C, DK 5000

Other trials in Denmark

Poland3 sites

Novartis Investigative Site
Bialystok, 15-044
Novartis Investigative Site
Lodz, 90 153
Novartis Investigative Site
Warsaw, 01-138

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Czechia2 sites

Novartis Investigative Site
Brno, 625 00
Novartis Investigative Site
Olomouc, 779 00

Other trials in Czechia

United Kingdom2 sites

Novartis Investigative Site
Edinburgh, EH1 1BE
Novartis Investigative Site
London, SW3 6PH

Other trials in United Kingdom

About this study

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

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.

Read the 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

Conditions: Pulmonary Sarcoidosis
Being tested: CMK389, Placebo
Keywords: chronic pulmonary sarcoidosis
Medical subject headings: Sarcoidosis, Pulmonary

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

CMK389Drug
single i.v. dose every 4 weeks
PlaceboDrug
single i.v. dose every 4 weeks

Study groups in NCT04064242
Study group	Role	What they receive
CMK389	Experimental	CMK389 10 mg/kg i.v. every 4 weeks for a total of 4 doses Receives: Drug: CMK389
Placebo	Placebo comparator	Placebo i.v. every 4 weeks for a total of 4 doses Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Baseline, Week 16

Secondary outcomes (8)

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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline, Week 16

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

23 Sep 202012 Dec 2023

First posted21 Aug 2019
Study start23 Sep 2020
Primary completion19 Sep 2023
Study completion12 Dec 2023

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Pulmonary SarcoidosisStudies of the same condition, open and under way.
More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Model description: Participants will be assigned to one of two treatment arms, either CMK389 or placebo.
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 62 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04064242
Sponsor's protocol ID: CCMK389X2201
Status last verified: Apr 2025
First submitted: 20 Aug 2019
Last updated: 13 Apr 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: 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.

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingObservational study
Role of Genetic Factors in the Development of Lung Disease
Cystic Fibrosis, Pulmonary Fibrosis
Not yet recruitingPhase 2
An Efficacy Study of XTMAB-16 in Patients With Pulmonary Sarcoidosis With or Without Extrapulmonary Manifestations
Pulmonary Sarcoidosis
Not yet recruitingPhase 2
LAM-001 for the Treatment of Sarcoidosis Associated Pulmonary Hypertension (SAPH)
Sarcoidosis Associated Pulmonary Hypertension
Not yet recruitingPhase 2/3
Evaluation of the Efficacy and Safety of Compound Betamethasone in Pulmonary Sarcoidosis
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Not yet recruitingPhase 2
A Clinical Trial of Tulisokibart (MK-7240) in Participants With Pulmonary Sarcoidosis (MK-7240-016)
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All Pulmonary Sarcoidosis trials

Study at a glance

From the registry record, last updated by the sponsor on 13 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT04064242
Acronym / sponsor ID: CCMK389X2201
Conditions: Pulmonary Sarcoidosis
Keywords: chronic pulmonary sarcoidosis
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 62 participants (actual)
Lead sponsor: Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
Study start: 23 Sep 2020 (actual)
Primary completion: 19 Sep 2023 (actual)
Study completion: 12 Dec 2023 (actual)
First posted: 21 Aug 2019 (actual)
Results: Posted 2 Oct 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2
Model description: Participants will be assigned to one of two treatment arms, either CMK389 or placebo.

Arm	Type	Receives
CMK389	Experimental	Drug: CMK389CMK389 10 mg/kg i.v. every 4 weeks for a total of 4 doses
Placebo	Placebo comparator	Drug: PlaceboPlacebo i.v. every 4 weeks for a total of 4 doses

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

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.

Key exclusion criteria (13 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
CMK389single i.v. dose every 4 weeks	Drug	CMK389
Placebosingle i.v. dose every 4 weeks	Drug	Placebo

Primary outcome

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.

8 secondary outcomes

Number of Participants Who Had an Increase in Steroid Usage From Baseline to 16 Weeks of Treatment
Time frame: Baseline, Week 16
Number of Participants Who Deteriorate From Baseline to 16 Weeks of Treatment
Time frame: Baseline, Week 16
Percent Change in [18F]-FDG-PET/CT (SUVmax and SUVmean) From Baseline to 16 Weeks of Treatment
Time frame: Baseline, Week 16
The Observed Serum Concentration Following CMK389 Administration at End of Infusion
Time frame: Post 1 hour: Day 1, Day 29, Day 57, Day 85
Pre-dose Trough Concentration (Ctrough) of CMK389
Time frame: Pre-dose: Day 1, Day 29, Day 57, Day 85
Change in FEV1 From Baseline to 16 Weeks of Treatment
Time frame: Baseline, Week 16
Change in Diffusion Capacity of the Lung for Carbon Monoxide (DLCO) From Baseline to 16 Weeks of Treatment
Time frame: Baseline, Week 16
Change in 6-minute Walk Distance (6MWD) From Baseline to 16 Weeks of Treatment
Time frame: Baseline, Week 16

Results and safety

Results posted to the registry on 2 Oct 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
CMK389 10 mg/kg i.v.	31	31
Placebo i.v.	31	31

Primary outcome: Change in Percent Predicted FVC From Baseline to 16 Weeks of Treatment

Time frame: Baseline, Week 16. Mean (Standard Deviation). Unit: Percent predicted

Measure	CMK389 10 mg/kg i.v. n = 26	Placebo i.v. n = 27
Value	-0.48 (1.17)	1.02 (1.13)

CMK389 10 mg/kg i.v. vs Placebo i.v.: Posterior estimate treatment difference: -1.49 (80% CI -3.56 to 0.60), p = 0.1804, Bayesian analysis

Population analysed: The Pharmacodynamic (PD) analysis set included all patients with available PD data and no protocol deviations with relevant impact on PD data. Data collected after a change of the steroid dose not based on the clinical status evaluation (CSE) algorithm were excluded from the analysis set if assessed as having a potentially relevant impact on PD data.

8 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 197 days... Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
CMK389 10 mg/kg i.v	2 of 31 (6.5%)	21 of 31 (67.7%)	0 of 31
Placebo i.v	0 of 31 (0%)	19 of 31 (61.3%)	0 of 31
Total	2 of 62 (3.2%)	40 of 62 (64.5%)	0 of 62

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 13 Apr 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
A Plain Language Trial Summary is available on www.novctrd.comLink provided by the sponsor.
Individual participant dataSharing planned: Yes. 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.

Related trials for Pulmonary Sarcoidosis

RecruitingObservational study
Role of Genetic Factors in the Development of Lung Disease
Cystic Fibrosis, Pulmonary Fibrosis
Not yet recruitingPhase 2
An Efficacy Study of XTMAB-16 in Patients With Pulmonary Sarcoidosis With or Without Extrapulmonary Manifestations
Pulmonary Sarcoidosis
Not yet recruitingPhase 2
LAM-001 for the Treatment of Sarcoidosis Associated Pulmonary Hypertension (SAPH)
Sarcoidosis Associated Pulmonary Hypertension
Not yet recruitingPhase 2/3
Evaluation of the Efficacy and Safety of Compound Betamethasone in Pulmonary Sarcoidosis
Sarcoidosis, Pulmonary
Not yet recruitingPhase 2
A Clinical Trial of Tulisokibart (MK-7240) in Participants With Pulmonary Sarcoidosis (MK-7240-016)
Pulmonary Sarcoidosis

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

22 sites in 6 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing CMK389 in people with Pulmonary Sarcoidosis, run by Novartis Pharmaceuticals at 22 sites in 6 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 22 sites in United States, Germany, Denmark, Poland, Czechia and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Oct 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Percent Predicted FVC From Baseline to 16 Weeks of Treatment (time frame: Baseline, Week 16). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04064242.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Apr 2025.