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

Phase 2

Terminated

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

Interventions: Drug: CC-90001
Other: Placebo

Registration Number: NCT03142191

Lead Sponsor: Celgene

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 138

Inclusion Criteria

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

Subject is male or female ≥ 40 years of age
Diagnosis of IPF is supported by HRCT and historical lung biopsy (surgical lung biopsy [SLB] or cryobiopsy) if available according to guidelines.
No features supporting an alternative diagnosis on transbronchial biopsy, bronchoalveolar lavage (BAL), or SLB, if performed.
Percent predicted forced vital capacity (% FVC) ≥ 45% and ≤ 95% at Screening
Percent predicted diffusion capacity of the lung for carbon monoxide (DLCO) ≥ 25% and ≤ 90% predicted at Screening.
Able to walk ≥ 150 meters during the 6-minute walk test (6MWT) at Screening
Females of childbearing potential (FCBP) must commit to true abstinence or agree to use two effective birth control methods.
Male subjects must practice true abstinence or use a barrier method of contraception.
Additional inclusion criteria apply.

Progressive Pulmonary Fibrosis (PPF) Sub-Study:

Met all inclusion criteria described for IPF subjects other than Inclusion Criterion 5.
Features of diffuse fibrosing lung disease of > 10% on HRCT by central reading.
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:

Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
Subject with a QTcF > 450 msec.
Evidence of clinically relevant airways obstruction at Screening.
Subjects using therapy targeted to treat IPF.
History of latent or active TB, unless there is medical record documentation of successful completion of a standard course of treatment
History of hepatitis B and/or hepatitis C, including those considered successfully treated/cured
Pregnancy or lactation.
Additional exclusion criteria apply.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CC-90001 200 mg PO QD	CC-90001	55 subjects will be randomized to CC-90001 200mg
CC-90001 400 mg PO QD	CC-90001	55 subjects will be randomized to CC-90001 400mg
Placebo PO QD	Placebo	55 subjects will be randomized to placebo
CC-90001 400 mg PO QD- Sub-Study	CC-90001	30 subjects will be randomized to CC-90001 400mg
Placebo PO QD- Sub-Study	Placebo	15 subjects will be randomized to placebo

Primary Outcome Measures

Name	Time	Method
Percentage Point Difference in % Predicted Forced Vital Capacity (FVC).	from baseline to week 24	Mean change from baseline in percentage point difference in % predicted forced vital capacity (FVC) FAS population is defined as all randomized participants who received at least one dose of the investigational product. Baseline is defined as day 1 of treatment.

Secondary Outcome Measures

Name	Time	Method
Mean Change From Baseline in Absolute Forced Vital Capacity (FVC).	from baseline to week 24	Mean change from baseline in absolute FVC in the full analysis set (FAS) population. FAS population is defined as all randomized participants who received at least one dose of the investigational product. Baseline is defined as day 1 of treatment.
Mean Change in Distance Walked in the 6-minute Walk Test (6MWT)	From baseline up to week 104	Mean change in distance walked in the 6-minute Walk Test (6MWT) The 6MWT measures the distance a participant is able to walk on a hard, flat surface, over a total of six minutes. The time points which will be measured are from baseline to Week 24, Extension Week 52, Extension Week 76, Extension Week 104, Week 24 to extension (Ext) Week 52 and Week 24 to Ext Week 104 FAS population is defined as all randomized participants who received at least one dose of the investigational product. Baseline is defined as day 1 of treatment. Week 24 is the start of baseline of the active treatment extension period.
Mean Change From Baseline in Dyspnea Rating on Borg Scale	From baseline up to week 104	Mean change from baseline in dyspnea rating on Borg Scale after the 6MWT. The Borg scale ranges from 0 to 10. Where 0 is no dyspnea and a 10 is extremely strong dyspnea. The lower the number the better. The time points which will be measured are from baseline to Week 24, Extension Week 52, Extension Week 76, Extension Week 104, Week 24 to extension (Ext) Week 52 and Week 24 to Ext Week 104 FAS population is defined as all randomized participants who received at least one dose of the investigational product. Baseline is defined as day 1 of treatment. Week 24 is the start of baseline of the active treatment extension period.
Percentage of Participants Who Had Disease Progression	From Baseline up to week 24	Disease progression is defined as one or more of the following: * Death from respiratory failure, * Absolute decrease of ≥ 10% from baseline in % predicted FVC at two consecutive evaluations at a minimum of 4 weeks between evaluations * Decrease from baseline of ≥ 50 meters in 6MWT distance (in the absence of a readily explainable cause, such as injury or trauma). * Unexplained worsening hypoxemia (an absolute decrease from baseline of 4% or more in arterial oxygen saturation by pulse oximetry \[SpO2\]). FAS population is defined as all randomized participants who received at least one dose of the investigational product. Baseline is defined as day 1 of treatment.
Mean Change From Baseline in Total Score and Domains on the Saint George's Respiratory Questionnaire (SGRQ)	From Baseline up to week 24	The SGRQ is a quality of life health questionnaire that has been validated in IPF. It consists of 76 items in three domains: * Symptoms * Activity * Impact of disease on daily life A total score is calculated from 0 (no health impairment) to 100 (maximum health impairment). In addition to the total score, there is also a score for each domain: symptoms, activity, and impact which are scored 0-100. Each component score is derived by dividing the summed weights, unique for all questions, by the maximum possible weight.
Mean Change From Baseline in The University of California San Diego Shortness of Breath Questionnaire (UCSD-SOBQ)	From Baseline up to week 24	The UCSD-SOBQ is a 24-item dyspnea questionnaire that asks participants to rate themselves from 0 ("Not at all") to 5 ("Maximally or unable to do because of breathlessness") in two areas: 1) how short of breath they are while performing various activities (21 items); and 2) how much shortness of breath, fear of hurting themselves by overexerting, and fear of shortness of breath limit them in their daily lives (3 items). If the subject does not routinely perform the activity, they are asked to estimate the degree of shortness of breath anticipated. The UCSD-SOBQ is scored by summing responses across all 24 items to form a total score. Scores range from 0 to 120. The lower the score the better.
Number of Participants With Adverse Events at the End of the Active Treatment Phase	From re-randomization to end of treatment (approximately 84 weeks)	Number of participants with Adverse events at the end of the active treatment phase
Number of Participants With Adverse Events in the Placebo Controlled Period	from baseline to re-randomization (approximately 56 weeks for the IPF cohort and 28 weeks for the PPF cohort)	Number of participants with Adverse events
Number of Participants With Worst Changes in Hematology Laboratory Parameters During the Active Treatment Extension Period	From re-randomization to end of treatment (approximately 84 weeks)	Number of participants with worst changes in hematology laboratory parameters including: basophils, hemoglobin, lymphocytes, neutrophils and platelets.
Number of Participants With Worst Changes in Hematology Laboratory Parameters During the in the Placebo Controlled Period	from baseline to re-randomization (approximately 56 weeks for the IPF cohort and 28 weeks for the PPF cohort)	Number of participants with worst changes in hematology laboratory parameters including: basophils, hemoglobin, lymphocytes, neutrophils and platelets.
Number of Participants With a Change From Worst Post-baseline in Urinalysis Laboratory Analysis in the Active Treatment Extension Period	From re-randomization to end of treatment (approximately 84 weeks)	Number of participants who had a change from worst post- baseline in urinalysis laboratory analysis for the following measures: Erythrocytes, Leukocytes, Tubular Epithelial Cells
Number of Participants With a Change From Worst Post-baseline in Urinalysis Laboratory Analysis in the Placebo Controlled Period	from baseline to re-randomization (approximately 56 weeks for the IPF cohort and 28 weeks for the PPF cohort)	Number of participants who had a change from worst post- baseline in urinalysis laboratory analysis for the following measures: Erythrocytes, Leukocytes, Tubular Epithelial Cells
Mean Change From Baseline in Electrocardiogram Measurements in the Active Treatment Extension Period	From re-randomization to 4 week follow up after end of treatment (approximately 84 weeks)	Mean change from baseline in Electrocardiogram readings for the following measures: QT interval, QTcF interval, QTcB interval, PR interval, QRS duration and RR interval
Mean Change From Baseline in Electrocardiogram Measurements in the Placebo Controlled Period	from baseline to week 24	Mean change from baseline in Electrocardiogram readings for the following measures: QT interval, QTcF interval, QTcB interval, PR interval, QRS duration and RR interval
Number of Participants With Worst Increase From Baseline in Blood Pressure in the Active Extension Period	From re-randomization to 4 week follow up after end of treatment (approximately 84 weeks)	Number of participants with worst increase from baseline in systolic and diastolic blood pressure.
Number of Participants With Worst Increase From Baseline in Blood Pressure in the Placebo-controlled Period	from baseline to re-randomization (approximately 56 weeks for the IPF cohort and 28 weeks for the PPF cohort)	Number of participants with worst increase from baseline in systolic and diastolic blood pressure.

Trial Locations

Locations (112): Local Institution - 502
🇺🇸
Dallas, Texas, United States
University Hospitals Cleveland Medical Center
🇺🇸
Cleveland, Ohio, United States
University of Pittsburgh Medical Center
🇺🇸
Pittsburgh, Pennsylvania, United States
Communal Institution Dnipropetrovsk City Clinical Hospital #6 of Dnipropetrovsk Regional Council
🇺🇦
Dnipro, Ukraine
CI of Healthcare RCH - Center of Medical Emergency and Accident Medicine
🇺🇦
Kharkiv, Ukraine
Local Institution - 631
🇨🇴
Bogotá, Colombia
Centro Medico Imbanaco
🇨🇴
Cali, Colombia
Kaohsiung Medical University Hospital
🇨🇳
Kaohsiung, Taiwan
Ege Universitesi Tip Fakultesi Hastanesi Ege University Medical Faculty Hospital
🇹🇷
Bornova, Turkey
The Lung Centre Respiratory Clinic - Vancouver General Hospital Location
🇨🇦
Vancouver, British Columbia, Canada
Federal Medico-Biological Agency FMBA - Federal Research Clinical Center FGUZ Clinical Hospital No.
🇷🇺
Moscow, Russian Federation
Vvedenskaya Hospital
🇷🇺
St. Petersburg, Russian Federation
City clinical hospital No 9
🇷🇺
Izhevsk, Russian Federation
Local Institution - 623
🇨🇦
Windsor, Ontario, Canada
Spitalul Clinic de Pneumoftiziologie Leon Daniello Cluj Napoca
🇷🇴
Cluj-Napoca, Romania
State Institution National Scientific Center of Radiation Medicine of NAMS of Ukraine
🇺🇦
Kyiv, Ukraine
Istanbul Universitesi - Cerrahpasa Tip Fakultesi Cerrahpasa Medical Faculty
🇹🇷
Istanbul, Turkey
Local Institution - 598
🇬🇧
Newcastle, United Kingdom
Local Institution - 694
🇬🇧
Westbury-on-Trym/ Bristol, United Kingdom
Nizhny Novgorod Research Institute of Hygiene and Occupational Pathology
🇷🇺
Nizhny Novgorod, Russian Federation
AGAPLESION EV. KRANKENHAUS MITTELHESSEN gGmbH
🇩🇪
Giessen, Germany
University General Hospital of Alexandroupolis
🇬🇷
Alexandroupolis, Greece
General Hospital of Heraklion Benizeleio Pananeio
🇬🇷
Heraklion, Greece
Centro Especializado en Enfermedades Pulmonares
🇨🇴
Bogotá, Colombia
Local Institution - 667
🇷🇺
St. Petersburg, Russian Federation
Helios Klinikum Emil Von Behring
🇩🇪
Berlin, Germany
Dr. Syed Anees Medicine Professional Corporation
🇨🇦
Windsor, Ontario, Canada
University of Crete - University General Hospital of Heraklion
🇬🇷
Iraklio, Greece
Centro de Reumatologia y Ortopedia SAS
🇨🇴
Barranquilla, Colombia
SI F.H.Yanovskyi National Institute of Phthisiatry and Pulmonology of Academy of Medical Sciences
🇺🇦
Kyiv, Ukraine
Royal Victoria Infirmary
🇬🇧
Newcastle, United Kingdom
Norfolk and Norwich University Hospital
🇬🇧
Norwich, United Kingdom
Ruhrlandklinik University Hospital
🇩🇪
Essen, Germany
Pavlov First Saint Petersburg State Medical University
🇷🇺
Saint-Petersburg, Russian Federation
University General Hospital Attikon
🇬🇷
Haidari, Greece
Spitalul Clinic de Boli Infectioase si Pneumoftiziologie Dr. Victor Babes Timisoara
🇷🇴
Timisoara, Romania
Buddhist Dalin Tzu Chi General Hospital
🇨🇳
Dalin, Taiwan
China Medical University Hospital
🇨🇳
Taichung City, Taiwan
National Taiwan University Hospital
🇨🇳
Taipei, Zhongzheng Dist., Taiwan
Local Institution - 681
🇹🇷
Bornova, Turkey
Local Institution - 666
🇷🇺
Nizhny Novgorod, Russian Federation
Republican Hospital
🇷🇺
Petrozavodsk, Russian Federation
Uludag Universitesi Tip Fakultesi
🇹🇷
Bursa, Turkey
Hull and East Yorkshire Hospitals NHS Trust - Castle Hill Hospital
🇬🇧
Cottingham, United Kingdom
Local Institution - 697
🇬🇧
Norwich, United Kingdom
Saint-Petersburg State Institution of Healthcare
🇷🇺
St. Petersburg, Russian Federation
Regional Phthisiopulmonological Center
🇺🇦
Ivano-Frankivsk, Ukraine
The Leeds Teaching Hospitals NHS Trust - St James's University Hospital
🇬🇧
Leeds, United Kingdom
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
Institute for Respiratory Health Inc
🇦🇺
Nedlands, Western Australia, Australia
University of Florida
🇺🇸
Gainesville, Florida, United States
Duke University Health System - Duke Pulmonary Transplant Clinic
🇺🇸
Durham, North Carolina, United States
University of Cincinnati Medical Center
🇺🇸
Cincinnati, Ohio, United States
Izmir Dr.Suat Seren Chest Diseases Hospital
🇹🇷
Izmir, Turkey
FSBHI Clincial Research Institute of Phithisioplulmonoloyg
🇷🇺
Saint Petersburg, Russian Federation
Local Institution - 675
🇷🇺
Saratov, Russian Federation
Saratov Regional Clinical Hospital
🇷🇺
Saratov, Russian Federation
SAIH of Yaroslavl region Clinical Hospital for Emergency Medical Care n.a. N.V.Solovyev
🇷🇺
Yaroslavl, Russian Federation
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
Stanford University Pulmonary and Critical Care Clinic
🇺🇸
Stanford, California, United States
University of California Davis Health System
🇺🇸
Sacramento, California, United States
University of Miami and Sylvester Cancer Center
🇺🇸
Miami, Florida, United States
The Lung and Research Center, LLC
🇺🇸
Chesterfield, Missouri, United States
Mt. Sinai School of Medicine
🇺🇸
New York, New York, United States
Pulmonary & Sleep Center of Oklahoma
🇺🇸
Tulsa, Oklahoma, United States
Medical University of South Carolina
🇺🇸
Charleston, South Carolina, United States
Vanderbilt University Medical Center
🇺🇸
Nashville, Tennessee, United States
University of Vermont
🇺🇸
Burlington, Vermont, United States
University of Utah Health Care
🇺🇸
Salt Lake City, Utah, United States
Concord Repatriation General Hospital
🇦🇺
Concord, New South Wales, Australia
Local Institution - 608
🇦🇺
Camperdown, New South Wales, Australia
Incor - Instituto do Coracao HCFMUSP
🇧🇷
Sao Paulo, Brazil
Royal Prince Alfred Hospital
🇦🇺
Camperdown, 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
St Vincent Hospital - Sydney
🇦🇺
Darlinghurst, Australia
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 Andre, Brazil
Kelowna & Respiratory Allergy Clinic
🇨🇦
Kelowna, British Columbia, Canada
Waldburg-Zeil Kliniken -Fachkliniken Wangen
🇩🇪
Wangen Im Allgaeu, Germany
Universitatsklinikum Heidelberg
🇩🇪
Heidelberg, Germany
Democritus University of Thrace
🇬🇷
Alexandroupolis, Greece
Local Institution - 642
🇩🇪
Giessen, Germany
Ural State Medical Academy - Medical Association Novaya Bolnitsa
🇷🇺
Ekaterinburg, Russian Federation
Russian Academy of Medical Sciences RAMS - Central Scientific Research Institute of Tuberculosis CTR
🇷🇺
Moscow, Russian Federation
Federal State Budgetary Scientific Institution Research Institute for Complex Issues of Cardiovascul
🇷🇺
Kemerovo, Russian Federation
TSBIH Territorial Clinical Hospital
🇷🇺
Krasnoyarsk, Russian Federation
Kharkiv City Clinical Hospital #13
🇺🇦
Kharkiv, Ukraine
Birmingham Chest Clinic
🇬🇧
Birmingham, United Kingdom
Hinchingbrooke Hospital
🇬🇧
Huntingdon, United Kingdom
Aintree University Hospital
🇬🇧
Liverpool (Walton Centre), United Kingdom
University Hospitals of Leicester NHS Trust - Glenfield Hospital - Institute for Lung Health ILH
🇬🇧
Leicester, United Kingdom
University Hospital Llandough
🇬🇧
Llandough, United Kingdom
University College London Hospitals
🇬🇧
London, United Kingdom
The University of Nottingham - Nottingham Respiratory Research Unit NRRU
🇬🇧
Nottingham, United Kingdom
Southampton General Hospital
🇬🇧
Southhampton, United Kingdom
Salford Royal
🇬🇧
Salford, United Kingdom
Southmead Hospital
🇬🇧
Westbury-on-Trym/ Bristol, United Kingdom
Fiona Stanley Hospital
🇦🇺
Murdoch, Western Australia, Australia
Clinica de Pneumologia S/S
🇧🇷
Goiania, Goiás, Brazil
Local Institution - 621
🇨🇦
Kelowna, British Columbia, Canada
University of Louisville
🇺🇸
Louisville, Kentucky, United States
Baylor University Medical Center
🇺🇸
Dallas, Texas, United States
Local Institution - 620
🇨🇦
Vancouver, British Columbia, Canada