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

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04064242

Collaborator

(none)

Enrollment

Locations

Arms

38.9

Anticipated Duration (Months)

2.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Pulmonary Sarcoidosis	Drug: CMK389 Drug: Placebo	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

66 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Participants will be assigned to one of two treatment arms, either CMK389 or placebo.Participants will be assigned to one of two treatment arms, either CMK389 or placebo.

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Sep 23, 2020

Anticipated Primary Completion Date :

Oct 2, 2023

Anticipated Study Completion Date :

Dec 22, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CMK389 CMK389	Drug: CMK389 single i.v. dose every 4 weeks
Placebo Comparator: Placebo Placebo	Drug: Placebo single i.v. dose every 4 weeks

Arm

Intervention/Treatment

Experimental: CMK389

CMK389

Drug: CMK389

single i.v. dose every 4 weeks

Placebo Comparator: Placebo

Placebo

Drug: Placebo

single i.v. dose every 4 weeks

Outcome Measures

Primary Outcome Measures

Forced Vital Capacity [Baseline to Week 16]
Change in forced vital capacity, % of predicted, between CMK389 and placebo.

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Birmingham	Alabama	United States	35294-3300
2	Novartis Investigative Site	Denver	Colorado	United States	80206
3	Novartis Investigative Site	Gainesville	Florida	United States	32610
4	Novartis Investigative Site	Chicago	Illinois	United States	60611
5	Novartis Investigative Site	Kansas City	Kansas	United States	66160-7330
6	Novartis Investigative Site	Baltimore	Maryland	United States	21224
7	Novartis Investigative Site	New York	New York	United States	10029
8	Novartis Investigative Site	Greenville	North Carolina	United States	27858
9	Novartis Investigative Site	Cincinnati	Ohio	United States	45267
10	Novartis Investigative Site	Pittsburgh	Pennsylvania	United States	15213
11	Novartis Investigative Site	Brno Bohunice		Czechia	625 00
12	Novartis Investigative Site	Olomouc		Czechia	775 20
13	Novartis Investigative Site	Aarhus N		Denmark	8200
14	Novartis Investigative Site	Hellerup		Denmark	2900
15	Novartis Investigative Site	Odense C		Denmark	DK 5000
16	Novartis Investigative Site	Heidelberg	Baden-Württemberg	Germany	69126
17	Novartis Investigative Site	Berlin		Germany	13353
18	Novartis Investigative Site	Essen		Germany	45147
19	Novartis Investigative Site	Frankfurt		Germany	60596
20	Novartis Investigative Site	Hamburg		Germany	20246
21	Novartis Investigative Site	Hannover		Germany	30625
22	Novartis Investigative Site	Bialystok		Poland	15-044
23	Novartis Investigative Site	Lodz		Poland	90 153
24	Novartis Investigative Site	Warszawa		Poland	01-138
25	Novartis Investigative Site	Edinburgh		United Kingdom
26	Novartis Investigative Site	London		United Kingdom	SW3 6PH

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Novartis Pharmaceuticals

ClinicalTrials.gov Identifier:

NCT04064242

Other Study ID Numbers:

CCMK389X2201

First Posted:

Aug 21, 2019

Last Update Posted:

Aug 24, 2022

Last Verified:

Aug 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Novartis Pharmaceuticals

chronic pulmonary sarcoidosis

Additional relevant MeSH terms:

Sarcoidosis, Pulmonary

Sarcoidosis

Study Results

No Results Posted as of Aug 24, 2022