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

Lung Diseases Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03142191
• Other study ID #: CC-90001-IPF-001
• Secondary ID: 2016-003473-17U1
• Status: Terminated
• Phase: Phase 2
• Start date: July 26, 2017
• Est. completion date: December 24, 2021

Study information

• Verified date: June 2023
• Source: Celgene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 138
• Est. completion date: December 24, 2021
• Est. primary completion date: December 24, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

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

Other:
• Placebo
Placebo

Locations

Country	Name	City	State
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 - 608	Camperdown	New South Wales
Australia	Royal Prince Alfred Hospital	Camperdown	New South Wales
Australia	Concord Repatriation General Hospital	Concord	New South Wales
Australia	St Vincent Hospital - Sydney	Darlinghurst
Australia	Fiona Stanley Hospital	Murdoch	Western Australia
Australia	Institute for Respiratory Health Inc	Nedlands	Western Australia
Australia	Local Institution - 605	Parkville	Victoria
Australia	Royal Melbourne Hospital	Parkville	Victoria
Australia	Mater Medical Centre	South Brisbane	Queensland
Brazil	Clinica de Pneumologia S/S	Goiania	Goiás
Brazil	Hospital Ernesto Dornelles	Porto Alegre
Brazil	Hospital Nossa Senhora da Conceicao	Porto Alegre	Rio Grande Do Sul
Brazil	Irmandade da Santa Casa de Misericordia de Porto Alegre	Porto Alegre	Rio Grande Do Sul
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	Incor - Instituto do Coracao HCFMUSP	Sao Paulo
Canada	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
Colombia	Centro de Reumatologia y Ortopedia SAS	Barranquilla
Colombia	Centro Especializado en Enfermedades Pulmonares	Bogotá
Colombia	Local Institution - 631	Bogotá
Colombia	Centro Medico Imbanaco	Cali
Germany	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 Im Allgaeu
Greece	Democritus University of Thrace	Alexandroupolis
Greece	University General Hospital of Alexandroupolis	Alexandroupolis
Greece	University General Hospital Attikon	Haidari
Greece	General Hospital of Heraklion Benizeleio Pananeio	Heraklion
Greece	University of Crete - University General Hospital of Heraklion	Iraklio
Romania	Spitalul Clinic de Pneumoftiziologie Leon Daniello Cluj Napoca	Cluj-Napoca
Romania	Spitalul Clinic de Boli Infectioase si Pneumoftiziologie Dr. Victor Babes Timisoara	Timisoara
Russian Federation	Ural State Medical Academy - Medical Association Novaya Bolnitsa	Ekaterinburg
Russian Federation	City clinical hospital No 9	Izhevsk
Russian Federation	Federal State Budgetary Scientific Institution Research Institute for Complex Issues of Cardiovascul	Kemerovo
Russian Federation	TSBIH Territorial Clinical Hospital	Krasnoyarsk
Russian Federation	Federal Medico-Biological Agency FMBA - Federal Research Clinical Center FGUZ Clinical Hospital No.	Moscow
Russian Federation	Russian Academy of Medical Sciences RAMS - Central Scientific Research Institute of Tuberculosis CTR	Moscow
Russian Federation	Local Institution - 666	Nizhny Novgorod
Russian Federation	Nizhny Novgorod Research Institute of Hygiene and Occupational Pathology	Nizhny Novgorod
Russian Federation	Republican Hospital	Petrozavodsk
Russian Federation	FSBHI Clincial Research Institute of Phithisioplulmonoloyg	Saint Petersburg
Russian Federation	Pavlov First Saint Petersburg State Medical University	Saint-Petersburg
Russian Federation	Local Institution - 675	Saratov
Russian Federation	Saratov Regional Clinical Hospital	Saratov
Russian Federation	Local Institution - 667	St. Petersburg
Russian Federation	Saint-Petersburg State Institution of Healthcare	St. Petersburg
Russian Federation	Vvedenskaya Hospital	St. Petersburg
Russian Federation	SAIH of Yaroslavl region Clinical Hospital for Emergency Medical Care n.a. N.V.Solovyev	Yaroslavl
Taiwan	Buddhist Dalin Tzu Chi General Hospital	Dalin
Taiwan	Kaohsiung Medical University Hospital	Kaohsiung
Taiwan	China Medical University Hospital	Taichung City
Taiwan	National Taiwan University Hospital	Taipei, Zhongzheng Dist.
Turkey	Ege Universitesi Tip Fakultesi Hastanesi Ege University Medical Faculty Hospital	Bornova
Turkey	Local Institution - 681	Bornova
Turkey	Uludag Universitesi Tip Fakultesi	Bursa
Turkey	Istanbul Universitesi - Cerrahpasa Tip Fakultesi Cerrahpasa Medical Faculty	Istanbul
Turkey	Izmir Dr.Suat Seren Chest Diseases Hospital	Izmir
Ukraine	Communal Institution Dnipropetrovsk City Clinical Hospital #6 of Dnipropetrovsk Regional Council	Dnipro
Ukraine	Regional Phthisiopulmonological Center	Ivano-Frankivsk
Ukraine	CI of Healthcare RCH - Center of Medical Emergency and Accident Medicine	Kharkiv
Ukraine	Kharkiv City Clinical Hospital #13	Kharkiv
Ukraine	SI F.H.Yanovskyi National Institute of Phthisiatry and Pulmonology of Academy of Medical Sciences	Kyiv
Ukraine	State Institution National Scientific Center of Radiation Medicine of NAMS of Ukraine	Kyiv
United Kingdom	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 States	University of Vermont	Burlington	Vermont
United States	Medical University of South Carolina	Charleston	South Carolina
United States	The Lung and Research Center, LLC	Chesterfield	Missouri
United States	University of Cincinnati Medical Center	Cincinnati	Ohio
United States	University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	Baylor University Medical Center	Dallas	Texas
United States	Local Institution - 502	Dallas	Texas
United States	Duke University Health System - Duke Pulmonary Transplant Clinic	Durham	North Carolina
United States	University of Florida	Gainesville	Florida
United States	Loma Linda Univ Medical Center	Loma Linda	California
United States	Cedars Sinai Medical Center Rheumatology	Los Angeles	California
United States	University of Louisville	Louisville	Kentucky
United States	University of Miami and Sylvester Cancer Center	Miami	Florida
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Mt. Sinai School of Medicine	New York	New York
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Local Institution - 514	Sacramento	California
United States	University of California Davis Health System	Sacramento	California
United States	University of Utah Health Care	Salt Lake City	Utah
United States	Stanford University Pulmonary and Critical Care Clinic	Stanford	California
United States	Pulmonary & Sleep Center of Oklahoma	Tulsa	Oklahoma

Sponsors (1)

Lead Sponsor	Collaborator
Celgene

Countries where clinical trial is conducted

United States,  Australia,  Brazil,  Canada,  Colombia,  Germany,  Greece,  Romania,  Russian Federation,  Taiwan,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage Point Difference in % Predicted Forced Vital Capacity (FVC).	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.	from baseline to week 24
Secondary	Mean Change From Baseline in Absolute Forced Vital Capacity (FVC).	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.	from baseline to week 24
Secondary	Mean Change in Distance Walked in the 6-minute Walk Test (6MWT)	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.	From baseline up to week 104
Secondary	Mean Change From Baseline in Dyspnea Rating on Borg Scale	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.	From baseline up to week 104
Secondary	Percentage of Participants Who Had Disease Progression	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.	From Baseline up to week 24
Secondary	Mean Change From Baseline in Total Score and Domains on the Saint George's Respiratory Questionnaire (SGRQ)	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.	From Baseline up to week 24
Secondary	Mean Change From Baseline in The University of California San Diego Shortness of Breath Questionnaire (UCSD-SOBQ)	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.	From Baseline up to week 24
Secondary	Number of Participants With Adverse Events at the End of the Active Treatment Phase	Number of participants with Adverse events at the end of the active treatment phase	From re-randomization to end of treatment (approximately 84 weeks)
Secondary	Number of Participants With Adverse Events in the Placebo Controlled Period	Number of participants with Adverse events	from baseline to re-randomization (approximately 56 weeks for the IPF cohort and 28 weeks for the PPF cohort)
Secondary	Number of Participants With Worst Changes in Hematology Laboratory Parameters During the Active Treatment Extension Period	Number of participants with worst changes in hematology laboratory parameters including: basophils, hemoglobin, lymphocytes, neutrophils and platelets.	From re-randomization to end of treatment (approximately 84 weeks)
Secondary	Number of Participants With Worst Changes in Hematology Laboratory Parameters During the in the Placebo Controlled Period	Number of participants with worst changes in hematology laboratory parameters including: basophils, hemoglobin, lymphocytes, neutrophils and platelets.	from baseline to re-randomization (approximately 56 weeks for the IPF cohort and 28 weeks for the PPF cohort)
Secondary	Number of Participants With a Change From Worst Post-baseline in Urinalysis Laboratory Analysis in the Active Treatment Extension Period	Number of participants who had a change from worst post- baseline in urinalysis laboratory analysis for the following measures: Erythrocytes, Leukocytes, Tubular Epithelial Cells	From re-randomization to end of treatment (approximately 84 weeks)
Secondary	Number of Participants With a Change From Worst Post-baseline in Urinalysis Laboratory Analysis in the Placebo Controlled Period	Number of participants who had a change from worst post- baseline in urinalysis laboratory analysis for the following measures: Erythrocytes, Leukocytes, Tubular Epithelial Cells	from baseline to re-randomization (approximately 56 weeks for the IPF cohort and 28 weeks for the PPF cohort)
Secondary	Mean Change From Baseline in Electrocardiogram Measurements in the Active Treatment Extension Period	Mean change from baseline in Electrocardiogram readings for the following measures: QT interval, QTcF interval, QTcB interval, PR interval, QRS duration and RR interval	From re-randomization to 4 week follow up after end of treatment (approximately 84 weeks)
Secondary	Mean Change From Baseline in Electrocardiogram Measurements in the Placebo Controlled Period	Mean change from baseline in Electrocardiogram readings for the following measures: QT interval, QTcF interval, QTcB interval, PR interval, QRS duration and RR interval	from baseline to week 24
Secondary	Number of Participants With Worst Increase From Baseline in Blood Pressure in the Active Extension Period	Number of participants with worst increase from baseline in systolic and diastolic blood pressure.	From re-randomization to 4 week follow up after end of treatment (approximately 84 weeks)
Secondary	Number of Participants With Worst Increase From Baseline in Blood Pressure in the Placebo-controlled Period	Number of participants with worst increase from baseline in systolic and diastolic blood pressure.	from baseline to re-randomization (approximately 56 weeks for the IPF cohort and 28 weeks for the PPF cohort)

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