A Study to Evaluate the Efficacy and Safety of CC-90001 in Subjects With Idiopathic Pulmonary Fibrosis

NCT ID: NCT03142191

Last Updated: 2023-06-28

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 138 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-07-26
• Study Completion Date: 2021-12-24

Brief Summary

This is a Phase 2, multicenter, multinational, randomized, double-blind, placebo-controlled study evaluating the efficacy, safety, pharmacokinetics (PK), quality of life and exploratory pharmacodynamics (PD) of two treatment doses of CC-90001, 200 mg and 400 mg, compared with placebo, when delivered once daily per os (PO) in subjects with idiopathic pulmonary fibrosis (IPF). This study is designed to assess response to treatment by using measures of lung function, disease progression, fibrosis on radiography, and patient-reported outcomes. It will also assess dose response.

Detailed Description

Approximately 165 adult male and female subjects with a confirmed diagnosis of Idiopathic pulmonary fibrosis (IPF) (according to the most recent IPF guideline for diagnosis and management) will be randomized 1:1:1 (55 subjects per arm) to treatment with oral CC-90001or matching placebo for an initial 24 weeks.

The randomization will be stratified based on the concurrent administration of SOC (Yes/No). Subjects completing the 24-week Double-blind Treatment Phase will continue onto the 80-week Active Treatment Extension Phase. At Week 24, all subjects originally randomized to receive placebo will be re-randomized 1:1 to blinded CC-90001 (200 mg or 400 mg PO QD). During the 80-week Active Treatment Extension Phase, all subjects not on concurrent SOC therapy will have the opportunity, if deemed appropriate by the Investigator, to receive allowed standard of care (SOC).

The exploratory Progressive Pulmonary Fibrosis (PPF) sub study will evaluate the efficacy, safety, PK, quality of life and exploratory PD of one PO treatment dose regimen of CC-90001, compared with placebo, for an initial 24 weeks of treatment, in subjects with PPF and long-term safety in the 80-week Active Treatment Extension Phase when all PPF subjects will receive CC-90001. Approximately 45 non-SOC subjects will be randomized in this sub study.

All subjects who complete the study treatment phases and those subjects who discontinue investigational product (IP) prior to the completion of the study will participate in the 4-week Post-treatment Observational Follow-up Phase.

The study will be conducted in compliance with the International Council Harmonisation (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use/Good Clinical Practice (GCP) and applicable regulatory requirements.

An external DMC, comprised of independent physician experts and a statistician who are not affiliated with the Sponsor and for whom there is no identified conflict of interest will be responsible for safeguarding study participants' interests and for monitoring the overall conduct of the study.

Conditions

Idiopathic Pulmonary Fibrosis; Fibrosis; Idiopathic Interstitial Pneumonias; Pathologic Processes; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

CC-90001 400 mg PO QD

55 subjects will be randomized to CC-90001 400mg

Group Type: EXPERIMENTAL

CC-90001

Intervention Type: DRUG

CC-90001 is a potent, selective inhibitor of JNK.

CC-90001 200 mg PO QD

55 subjects will be randomized to CC-90001 200mg

Group Type: EXPERIMENTAL

CC-90001

Intervention Type: DRUG

CC-90001 is a potent, selective inhibitor of JNK.

Placebo PO QD

55 subjects will be randomized to placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Placebo

CC-90001 400 mg PO QD- Sub-Study

30 subjects will be randomized to CC-90001 400mg

Group Type: EXPERIMENTAL

CC-90001

Intervention Type: DRUG

CC-90001 is a potent, selective inhibitor of JNK.

Placebo PO QD- Sub-Study

15 subjects will be randomized to placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Placebo

Interventions

CC-90001

CC-90001 is a potent, selective inhibitor of JNK.

Intervention Type: DRUG

Placebo

Placebo

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

Subject understands and has voluntarily signed and dated an informed consent form

1. Subject is male or female ≥ 40 years of age

2. Diagnosis of IPF is supported by HRCT and historical lung biopsy (surgical lung biopsy [SLB] or cryobiopsy) if available according to guidelines.

3. No features supporting an alternative diagnosis on transbronchial biopsy, bronchoalveolar lavage (BAL), or SLB, if performed.

4. Percent predicted forced vital capacity (% FVC) ≥ 45% and ≤ 95% at Screening

5. Percent predicted diffusion capacity of the lung for carbon monoxide (DLCO) ≥ 25% and ≤ 90% predicted at Screening.

6. Able to walk ≥ 150 meters during the 6-minute walk test (6MWT) at Screening

7. Females of childbearing potential (FCBP) must commit to true abstinence or agree to use two effective birth control methods.

8. Male subjects must practice true abstinence or use a barrier method of contraception.

Progressive Pulmonary Fibrosis (PPF) Sub-Study:

2. Features of diffuse fibrosing lung disease of > 10% on HRCT by central reading.

3. Investigator-documented ≥ 5% annualized relative decline in FVC in past 24 months from Screening Visit 1

Exclusion Criteria

The presence of any of the following will exclude a subject from enrollment:

1. Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.

2. Subject with a QTcF > 450 msec.

3. Evidence of clinically relevant airways obstruction at Screening.

4. Subjects using therapy targeted to treat IPF.

5. History of latent or active TB, unless there is medical record documentation of successful completion of a standard course of treatment

6. History of hepatitis B and/or hepatitis C, including those considered successfully treated/cured

7. Pregnancy or lactation.

• Minimum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Celgene

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bristol-Myers Squibb

Role: STUDY_DIRECTOR

Bristol-Myers Squibb

Locations

Loma Linda Univ Medical Center

Loma Linda, California, United States

Cedars Sinai Medical Center Rheumatology

Los Angeles, California, United States

Local Institution - 514

Sacramento, California, United States

University of California Davis Health System

Sacramento, California, United States

Stanford University Pulmonary and Critical Care Clinic

Stanford, California, United States

University of Florida

Gainesville, Florida, United States

University of Miami and Sylvester Cancer Center

Miami, Florida, United States

University of Louisville

Louisville, Kentucky, United States

The Lung and Research Center, LLC

Chesterfield, Missouri, United States

Mt. Sinai School of Medicine

New York, New York, United States

Duke University Health System - Duke Pulmonary Transplant Clinic

Durham, North Carolina, United States

University of Cincinnati Medical Center

Cincinnati, Ohio, United States

University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States

Pulmonary & Sleep Center of Oklahoma

Tulsa, Oklahoma, United States

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Medical University of South Carolina

Charleston, South Carolina, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Baylor University Medical Center

Dallas, Texas, United States

Local Institution - 502

Dallas, Texas, United States

University of Utah Health Care

Salt Lake City, Utah, United States

University of Vermont

Burlington, Vermont, United States

Local Institution - 608

Camperdown, New South Wales, Australia

Royal Prince Alfred Hospital

Camperdown, New South Wales, Australia

Concord Repatriation General Hospital

Concord, New South Wales, Australia

Mater Medical Centre

South Brisbane, Queensland, Australia

Local Institution - 601

Adelaide, South Australia, Australia

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Flinders Medical Centre

Bedford Park, South Australia, Australia

Local Institution - 605

Parkville, Victoria, Australia

Royal Melbourne Hospital

Parkville, Victoria, Australia

Fiona Stanley Hospital

Murdoch, Western Australia, Australia

Institute for Respiratory Health Inc

Nedlands, Western Australia, Australia

St Vincent Hospital - Sydney

Darlinghurst, , Australia

Clinica de Pneumologia S/S

Goiânia, Goiás, Brazil

Irmandade da Santa Casa de Misericordia de Porto Alegre

Porto Alegre, Rio Grande do Sul, Brazil

Hospital Nossa Senhora da Conceicao

Porto Alegre, Rio Grande do Sul, Brazil

Hospital Ernesto Dornelles

Porto Alegre, , Brazil

Universidade Federal do Rio de Janeiro (UFRJ)-Hospital Universitario Clementino Fraga Filho (HUCFF)

Rio de Janeiro, , Brazil

Faculdade de Medicina do ABC

Santo André, , Brazil

Incor - Instituto do Coracao HCFMUSP

São Paulo, , Brazil

Kelowna & Respiratory Allergy Clinic

Kelowna, British Columbia, Canada

Local Institution - 621

Kelowna, British Columbia, Canada

Local Institution - 620

Vancouver, British Columbia, Canada

The Lung Centre Respiratory Clinic - Vancouver General Hospital Location

Vancouver, British Columbia, Canada

Dr. Syed Anees Medicine Professional Corporation

Windsor, Ontario, Canada

Local Institution - 623

Windsor, Ontario, Canada

Centro de Reumatologia y Ortopedia SAS

Barranquilla, , Colombia

Local Institution - 631

Bogotá, , Colombia

Centro Especializado en Enfermedades Pulmonares

Bogotá, , Colombia

Centro Medico Imbanaco

Cali, , Colombia

Helios Klinikum Emil Von Behring

Berlin, , Germany

Ruhrlandklinik University Hospital

Essen, , Germany

AGAPLESION EV. KRANKENHAUS MITTELHESSEN gGmbH

Giessen, , Germany

Local Institution - 642

Giessen, , Germany

Universitatsklinikum Heidelberg

Heidelberg, , Germany

Waldburg-Zeil Kliniken -Fachkliniken Wangen

Wangen, , Germany

Democritus University of Thrace

Alexandroupoli, , Greece

University General Hospital of Alexandroupolis

Alexandroupoli, , Greece

University General Hospital Attikon

Haidari, , Greece

University of Crete - University General Hospital of Heraklion

Heraklion, , Greece

General Hospital of Heraklion Benizeleio Pananeio

Heraklion, , Greece

Spitalul Clinic de Pneumoftiziologie Leon Daniello Cluj Napoca

Cluj-Napoca, , Romania

Spitalul Clinic de Boli Infectioase si Pneumoftiziologie Dr. Victor Babes Timisoara

Timișoara, , Romania

City clinical hospital No 9

Izhevsk, , Russia

Federal State Budgetary Scientific Institution Research Institute for Complex Issues of Cardiovascul

Kemerovo, , Russia

TSBIH Territorial Clinical Hospital

Krasnoyarsk, , Russia

Russian Academy of Medical Sciences RAMS - Central Scientific Research Institute of Tuberculosis CTR

Moscow, , Russia

Federal Medico-Biological Agency FMBA - Federal Research Clinical Center FGUZ Clinical Hospital No.

Moscow, , Russia

Local Institution - 666

Nizhny Novgorod, , Russia

Nizhny Novgorod Research Institute of Hygiene and Occupational Pathology

Nizhny Novgorod, , Russia

Republican Hospital

Petrozavodsk, , Russia

FSBHI Clincial Research Institute of Phithisioplulmonoloyg

Saint Petersburg, , Russia

Local Institution - 667

Saint Petersburg, , Russia

Vvedenskaya Hospital

Saint Petersburg, , Russia

Saint-Petersburg State Institution of Healthcare

Saint Petersburg, , Russia

Pavlov First Saint Petersburg State Medical University

Saint Petersburg, , Russia

Local Institution - 675

Saratov, , Russia

Saratov Regional Clinical Hospital

Saratov, , Russia

SAIH of Yaroslavl region Clinical Hospital for Emergency Medical Care n.a. N.V.Solovyev

Yaroslavl, , Russia

Ural State Medical Academy - Medical Association Novaya Bolnitsa

Yekaterinburg, , Russia

Buddhist Dalin Tzu Chi General Hospital

Dalin, , Taiwan

Kaohsiung Medical University Hospital

Kaohsiung City, , Taiwan

China Medical University Hospital

Taichung, , Taiwan

National Taiwan University Hospital

Taipei, Zhongzheng Dist., , Taiwan

Ege Universitesi Tip Fakultesi Hastanesi Ege University Medical Faculty Hospital

Bornova, , Turkey (Türkiye)

Local Institution - 681

Bornova, , Turkey (Türkiye)

Uludag Universitesi Tip Fakultesi

Bursa, , Turkey (Türkiye)

Istanbul Universitesi - Cerrahpasa Tip Fakultesi Cerrahpasa Medical Faculty

Istanbul, , Turkey (Türkiye)

Izmir Dr.Suat Seren Chest Diseases Hospital

Izmir, , Turkey (Türkiye)

Communal Institution Dnipropetrovsk City Clinical Hospital #6 of Dnipropetrovsk Regional Council

Dnipro, , Ukraine

Regional Phthisiopulmonological Center

Ivano-Frankivsk, , Ukraine

Kharkiv City Clinical Hospital #13

Kharkiv, , Ukraine

CI of Healthcare RCH - Center of Medical Emergency and Accident Medicine

Kharkiv, , Ukraine

State Institution National Scientific Center of Radiation Medicine of NAMS of Ukraine

Kyiv, , Ukraine

SI F.H.Yanovskyi National Institute of Phthisiatry and Pulmonology of Academy of Medical Sciences

Kyiv, , Ukraine

Birmingham Chest Clinic

Birmingham, , United Kingdom

Hull and East Yorkshire Hospitals NHS Trust - Castle Hill Hospital

Cottingham, , United Kingdom

Hinchingbrooke Hospital

Huntingdon, , United Kingdom

The Leeds Teaching Hospitals NHS Trust - St James's University Hospital

Leeds, , United Kingdom

University Hospitals of Leicester NHS Trust - Glenfield Hospital - Institute for Lung Health ILH

Leicester, , United Kingdom

Aintree University Hospital

Liverpool (Walton Centre), , United Kingdom

University Hospital Llandough

Llandough, , United Kingdom

University College London Hospitals

London, , United Kingdom

Local Institution - 598

Newcastle, , United Kingdom

Royal Victoria Infirmary

Newcastle, , United Kingdom

Local Institution - 697

Norwich, , United Kingdom

Norfolk and Norwich University Hospital

Norwich, , United Kingdom

The University of Nottingham - Nottingham Respiratory Research Unit NRRU

Nottingham, , United Kingdom

Salford Royal

Salford, , United Kingdom

Southampton General Hospital

Southhampton, , United Kingdom

Local Institution - 694

Westbury-on-Trym/ Bristol, , United Kingdom

Southmead Hospital

Westbury-on-Trym/ Bristol, , United Kingdom

Countries

United States; Australia; Brazil; Canada; Colombia; Germany; Greece; Romania; Russia; Taiwan; Turkey (Türkiye); Ukraine; United Kingdom

References

Mattos WLLD, Khalil N, Spencer LG, Bonella F, Folz RJ, Rolf JD, Mogulkoc N, Lancaster LH, Jenkins RG, Lynch DA, Noble PW, Maher TM, Cottin V, Senger S, Horan GS, Greenberg S, Popmihajlov Z. Phase 2, Double-Blind, Placebo-controlled Trial of a c-Jun N-Terminal Kinase Inhibitor in Idiopathic Pulmonary Fibrosis. Am J Respir Crit Care Med. 2024 Aug 15;210(4):435-443. doi: 10.1164/rccm.202310-1907OC.

Reference Type: DERIVED

PMID: 38484130 (View on PubMed)

Popmihajlov Z, Sutherland DJ, Horan GS, Ghosh A, Lynch DA, Noble PW, Richeldi L, Reiss TF, Greenberg S. CC-90001, a c-Jun N-terminal kinase (JNK) inhibitor, in patients with pulmonary fibrosis: design of a phase 2, randomised, placebo-controlled trial. BMJ Open Respir Res. 2022 Jan;9(1):e001060. doi: 10.1136/bmjresp-2021-001060.

Reference Type: DERIVED

PMID: 35058236 (View on PubMed)

Nagy MA, Hilgraf R, Mortensen DS, Elsner J, Norris S, Tikhe J, Yoon W, Paisner D, Delgado M, Erdman P, Haelewyn J, Khambatta G, Xu L, Romanow WJ, Condroski K, Bahmanyar S, McCarrick M, Benish B, Blease K, LeBrun L, Moghaddam MF, Apuy J, Canan SS, Bennett BL, Satoh Y. Discovery of the c-Jun N-Terminal Kinase Inhibitor CC-90001. J Med Chem. 2021 Dec 23;64(24):18193-18208. doi: 10.1021/acs.jmedchem.1c01716. Epub 2021 Dec 13.

Reference Type: DERIVED

PMID: 34894681 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html

BMS Clinical Trial Information

https://www.bmsstudyconnect.com/s/US/English/USenHome

BMS Clinical Trial Patient Recruiting

https://www.fda.gov/Safety/MedWatch/SafetyInformation/default.htm

FDA Safety Alerts and Recalls

Other Identifiers

2016-003473-17

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1192-8549

Identifier Type: REGISTRY

Identifier Source: secondary_id

CC-90001-IPF-001

Identifier Type: -

Identifier Source: org_study_id