Clinical trial NCT03142191: A Study to Evaluate the Efficacy and Safety of CC-90001 in Subjects With Idiopathic Pulmonary Fibrosis
Official title: A Phase 2, 24-Week, Randomized, Double-blind, Placebo-controlled, Multicenter Study, With an 80-Week Active Treatment Extension, to Evaluate the Efficacy and Safety of CC-90001 in Subjects With Idiopathic Pulmonary Fibrosis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Idiopathic Pulmonary Fibrosis
Fibrosis
Idiopathic Interstitial Pneumonias
Pathologic Processes
Lung Diseases, Interstitial
Lung Diseases
Respiratory Tract Diseases
Keywords: Idiopathic Pulmonary Fibrosis (IPF)
Pulmonary Fibrosis
CC-90001
Safety
Efficacy
IPF
idiopathic pulmonary fibrosis
Lead sponsor: Celgene
Sponsor class: INDUSTRY
First posted: 2017-05-05
Enrollment: 138
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.
9. Additional inclusion criteria apply.

Progressive Pulmonary Fibrosis (PPF) Sub-Study:

1. Met all inclusion criteria described for IPF subjects other than Inclusion Criterion 5.
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.
8. Additional exclusion criteria apply.

Primary outcomes:
measure: Percentage Point Difference in % Predicted Forced Vital Capacity (FVC).
timeFrame: from baseline to week 24
Secondary outcomes:
measure: Mean Change From Baseline in Absolute Forced Vital Capacity (FVC).
timeFrame: from baseline to week 24
measure: Mean Change in Distance Walked in the 6-minute Walk Test (6MWT)
timeFrame: From baseline up to week 104
measure: Mean Change From Baseline in Dyspnea Rating on Borg Scale
timeFrame: From baseline up to week 104
measure: Percentage of Participants Who Had Disease Progression
timeFrame: From Baseline up to week 24
measure: Mean Change From Baseline in Total Score and Domains on the Saint George's Respiratory Questionnaire (SGRQ)
timeFrame: From Baseline up to week 24
measure: Mean Change From Baseline in The University of California San Diego Shortness of Breath Questionnaire (UCSD-SOBQ)
timeFrame: From Baseline up to week 24
measure: Number of Participants With Adverse Events at the End of the Active Treatment Phase
timeFrame: From re-randomization to end of treatment (approximately 84 weeks)
measure: Number of Participants With Adverse Events in the Placebo Controlled Period
timeFrame: from baseline to re-randomization (approximately 56 weeks for the IPF cohort and 28 weeks for the PPF cohort)
measure: Number of Participants With Worst Changes in Hematology Laboratory Parameters During the Active Treatment Extension Period
timeFrame: From re-randomization to end of treatment (approximately 84 weeks)
measure: Number of Participants With Worst Changes in Hematology Laboratory Parameters During the in the Placebo Controlled Period
timeFrame: from baseline to re-randomization (approximately 56 weeks for the IPF cohort and 28 weeks for the PPF cohort)
measure: Number of Participants With a Change From Worst Post-baseline in Urinalysis Laboratory Analysis in the Active Treatment Extension Period
timeFrame: From re-randomization to end of treatment (approximately 84 weeks)
measure: Number of Participants With a Change From Worst Post-baseline in Urinalysis Laboratory Analysis in the Placebo Controlled Period
timeFrame: from baseline to re-randomization (approximately 56 weeks for the IPF cohort and 28 weeks for the PPF cohort)
measure: Mean Change From Baseline in Electrocardiogram Measurements in the Active Treatment Extension Period
timeFrame: From re-randomization to 4 week follow up after end of treatment (approximately 84 weeks)
measure: Mean Change From Baseline in Electrocardiogram Measurements in the Placebo Controlled Period
timeFrame: from baseline to week 24
measure: Number of Participants With Worst Increase From Baseline in Blood Pressure in the Active Extension Period
timeFrame: From re-randomization to 4 week follow up after end of treatment (approximately 84 weeks)
measure: Number of Participants With Worst Increase From Baseline in Blood Pressure in the Placebo-controlled Period
timeFrame: from baseline to re-randomization (approximately 56 weeks for the IPF cohort and 28 weeks for the PPF cohort)
Other outcomes:
Locations:
city: Loma Linda
country: United States
facility: Loma Linda Univ Medical Center
state: California
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center Rheumatology
state: California
city: Sacramento
country: United States
facility: Local Institution - 514
state: California
city: Sacramento
country: United States
facility: University of California Davis Health System
state: California
city: Stanford
country: United States
facility: Stanford University Pulmonary and Critical Care Clinic
state: California
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Miami
country: United States
facility: University of Miami and Sylvester Cancer Center
state: Florida
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: Chesterfield
country: United States
facility: The Lung and Research Center, LLC
state: Missouri
city: New York
country: United States
facility: Mt. Sinai School of Medicine
state: New York
city: Durham
country: United States
facility: Duke University Health System - Duke Pulmonary Transplant Clinic
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Tulsa
country: United States
facility: Pulmonary & Sleep Center of Oklahoma
state: Oklahoma
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: Dallas
country: United States
facility: Local Institution - 502
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Health Care
state: Utah
city: Burlington
country: United States
facility: University of Vermont
state: Vermont
city: Camperdown
country: Australia
facility: Local Institution - 608
state: New South Wales
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Concord
country: Australia
facility: Concord Repatriation General Hospital
state: New South Wales
city: South Brisbane
country: Australia
facility: Mater Medical Centre
state: Queensland
city: Adelaide
country: Australia
facility: Local Institution - 601
state: South Australia
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Parkville
country: Australia
facility: Local Institution - 605
state: Victoria
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Murdoch
country: Australia
facility: Fiona Stanley Hospital
state: Western Australia
city: Nedlands
country: Australia
facility: Institute for Respiratory Health Inc
state: Western Australia
city: Darlinghurst
country: Australia
facility: St Vincent Hospital - Sydney
city: Goiania
country: Brazil
facility: Clinica de Pneumologia S/S
state: Goiás
city: Porto Alegre
country: Brazil
facility: Irmandade da Santa Casa de Misericordia de Porto Alegre
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Hospital Nossa Senhora da Conceicao
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Hospital Ernesto Dornelles
city: Rio de Janeiro
country: Brazil
facility: Universidade Federal do Rio de Janeiro (UFRJ)-Hospital Universitario Clementino Fraga Filho (HUCFF)
city: Santo Andre
country: Brazil
facility: Faculdade de Medicina do ABC
city: Sao Paulo
country: Brazil
facility: Incor - Instituto do Coracao HCFMUSP
city: Kelowna
country: Canada
facility: Kelowna & Respiratory Allergy Clinic
state: British Columbia
city: Kelowna
country: Canada
facility: Local Institution - 621
state: British Columbia
city: Vancouver
country: Canada
facility: Local Institution - 620
state: British Columbia
city: Vancouver
country: Canada
facility: The Lung Centre Respiratory Clinic - Vancouver General Hospital Location
state: British Columbia
city: Windsor
country: Canada
facility: Dr. Syed Anees Medicine Professional Corporation
state: Ontario
city: Windsor
country: Canada
facility: Local Institution - 623
state: Ontario
city: Barranquilla
country: Colombia
facility: Centro de Reumatologia y Ortopedia SAS
city: Bogotá
country: Colombia
facility: Local Institution - 631
city: Bogotá
country: Colombia
facility: Centro Especializado en Enfermedades Pulmonares
city: Cali
country: Colombia
facility: Centro Medico Imbanaco
city: Berlin
country: Germany
facility: Helios Klinikum Emil Von Behring
city: Essen
country: Germany
facility: Ruhrlandklinik University Hospital
city: Giessen
country: Germany
facility: AGAPLESION EV. KRANKENHAUS MITTELHESSEN gGmbH
city: Giessen
country: Germany
facility: Local Institution - 642
city: Heidelberg
country: Germany
facility: Universitatsklinikum Heidelberg
city: Wangen Im Allgaeu
country: Germany
facility: Waldburg-Zeil Kliniken -Fachkliniken Wangen
city: Alexandroupolis
country: Greece
facility: Democritus University of Thrace
city: Alexandroupolis
country: Greece
facility: University General Hospital of Alexandroupolis
city: Haidari
country: Greece
facility: University General Hospital Attikon
city: Heraklion
country: Greece
facility: General Hospital of Heraklion Benizeleio Pananeio
city: Iraklio
country: Greece
facility: University of Crete - University General Hospital of Heraklion
city: Cluj-Napoca
country: Romania
facility: Spitalul Clinic de Pneumoftiziologie Leon Daniello Cluj Napoca
city: Timisoara
country: Romania
facility: Spitalul Clinic de Boli Infectioase si Pneumoftiziologie Dr. Victor Babes Timisoara
city: Ekaterinburg
country: Russian Federation
facility: Ural State Medical Academy - Medical Association Novaya Bolnitsa
city: Izhevsk
country: Russian Federation
facility: City clinical hospital No 9
city: Kemerovo
country: Russian Federation
facility: Federal State Budgetary Scientific Institution Research Institute for Complex Issues of Cardiovascul
city: Krasnoyarsk
country: Russian Federation
facility: TSBIH Territorial Clinical Hospital
city: Moscow
country: Russian Federation
facility: Russian Academy of Medical Sciences RAMS - Central Scientific Research Institute of Tuberculosis CTR
city: Moscow
country: Russian Federation
facility: Federal Medico-Biological Agency FMBA - Federal Research Clinical Center FGUZ Clinical Hospital No.
city: Nizhny Novgorod
country: Russian Federation
facility: Local Institution - 666
city: Nizhny Novgorod
country: Russian Federation
facility: Nizhny Novgorod Research Institute of Hygiene and Occupational Pathology
city: Petrozavodsk
country: Russian Federation
facility: Republican Hospital
city: Saint Petersburg
country: Russian Federation
facility: FSBHI Clincial Research Institute of Phithisioplulmonoloyg
city: Saint-Petersburg
country: Russian Federation
facility: Pavlov First Saint Petersburg State Medical University
city: Saratov
country: Russian Federation
facility: Local Institution - 675
city: Saratov
country: Russian Federation
facility: Saratov Regional Clinical Hospital
city: St. Petersburg
country: Russian Federation
facility: Local Institution - 667
city: St. Petersburg
country: Russian Federation
facility: Vvedenskaya Hospital
city: St. Petersburg
country: Russian Federation
facility: Saint-Petersburg State Institution of Healthcare
city: Yaroslavl
country: Russian Federation
facility: SAIH of Yaroslavl region Clinical Hospital for Emergency Medical Care n.a. N.V.Solovyev
city: Dalin
country: Taiwan
facility: Buddhist Dalin Tzu Chi General Hospital
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Hospital
city: Taichung City
country: Taiwan
facility: China Medical University Hospital
city: Taipei, Zhongzheng Dist.
country: Taiwan
facility: National Taiwan University Hospital
city: Bornova
country: Turkey
facility: Ege Universitesi Tip Fakultesi Hastanesi Ege University Medical Faculty Hospital
city: Bornova
country: Turkey
facility: Local Institution - 681
city: Bursa
country: Turkey
facility: Uludag Universitesi Tip Fakultesi
city: Istanbul
country: Turkey
facility: Istanbul Universitesi - Cerrahpasa Tip Fakultesi Cerrahpasa Medical Faculty
city: Izmir
country: Turkey
facility: Izmir Dr.Suat Seren Chest Diseases Hospital
city: Dnipro
country: Ukraine
facility: Communal Institution Dnipropetrovsk City Clinical Hospital #6 of Dnipropetrovsk Regional Council
city: Ivano-Frankivsk
country: Ukraine
facility: Regional Phthisiopulmonological Center
city: Kharkiv
country: Ukraine
facility: Kharkiv City Clinical Hospital #13
city: Kharkiv
country: Ukraine
facility: CI of Healthcare RCH - Center of Medical Emergency and Accident Medicine
city: Kyiv
country: Ukraine
facility: State Institution National Scientific Center of Radiation Medicine of NAMS of Ukraine
city: Kyiv
country: Ukraine
facility: SI F.H.Yanovskyi National Institute of Phthisiatry and Pulmonology of Academy of Medical Sciences
city: Birmingham
country: United Kingdom
facility: Birmingham Chest Clinic
city: Cottingham
country: United Kingdom
facility: Hull and East Yorkshire Hospitals NHS Trust - Castle Hill Hospital
city: Huntingdon
country: United Kingdom
facility: Hinchingbrooke Hospital
city: Leeds
country: United Kingdom
facility: The Leeds Teaching Hospitals NHS Trust - St James's University Hospital
city: Leicester
country: United Kingdom
facility: University Hospitals of Leicester NHS Trust - Glenfield Hospital - Institute for Lung Health ILH
city: Liverpool (Walton Centre)
country: United Kingdom
facility: Aintree University Hospital
city: Llandough
country: United Kingdom
facility: University Hospital Llandough
city: London
country: United Kingdom
facility: University College London Hospitals
city: Newcastle
country: United Kingdom
facility: Local Institution - 598
city: Newcastle
country: United Kingdom
facility: Royal Victoria Infirmary
city: Norwich
country: United Kingdom
facility: Local Institution - 697
city: Norwich
country: United Kingdom
facility: Norfolk and Norwich University Hospital
city: Nottingham
country: United Kingdom
facility: The University of Nottingham - Nottingham Respiratory Research Unit NRRU
city: Salford
country: United Kingdom
facility: Salford Royal
city: Southhampton
country: United Kingdom
facility: Southampton General Hospital
city: Westbury-on-Trym/ Bristol
country: United Kingdom
facility: Local Institution - 694
city: Westbury-on-Trym/ Bristol
country: United Kingdom
facility: Southmead Hospital
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.