A Study to Evaluate the Efficacy and Safety of CC-90001 i... | NCT03142191 | Trialant
NCT03142191
Sponsor
Celgene
Status
Terminated
Last Update Posted
Jun 28, 2023Actual
Enrollment
138Actual
Phase
Phase 2
Conditions
Idiopathic Pulmonary Fibrosis
Fibrosis
Idiopathic Interstitial Pneumonias
Pathologic Processes
Lung Diseases, Interstitial
Lung Diseases
Respiratory Tract Diseases
Interventions
CC-90001
Placebo
Countries
United States
Australia
Brazil
Canada
Colombia
Germany
Greece
Romania
Russia
Taiwan
Turkey (Türkiye)
Ukraine
United Kingdom
Protocol Section
Identification Module
NCT ID
NCT03142191
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
CC-90001-IPF-001
Secondary IDs
ID
Type
Description
Link
2016-003473-17
EudraCT Number
U1111-1192-8549
Registry Identifier
WHO
Brief Title
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
Acronym
Not provided
Organization
CelgeneINDUSTRY
Status Module
Record Verification Date
Jun 2023
Overall Recruitment Status or Expanded Access Status
Terminated
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Business objectives have changed.
Expanded Access Info
No
Start Date
Jul 26, 2017Actual
Primary Completion Date
Dec 24, 2021Actual
Completion Date
Dec 24, 2021Actual
First Submitted Date
Apr 24, 2017
First Submission Date that Met QC Criteria
May 3, 2017
First Posted Date
May 5, 2017Actual
Results Waived
Not provided
Results First Submitted Date
Dec 22, 2022
Results First Submitted that Met QC Criteria
Jun 6, 2023
Results First Posted Date
Jun 28, 2023Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Jun 6, 2023
Last Update Posted Date
Jun 28, 2023Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
CelgeneINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
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 Module
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
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
138Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
CC-90001 400 mg PO QD
Experimental
55 subjects will be randomized to CC-90001 400mg
Drug: CC-90001
CC-90001 200 mg PO QD
Experimental
55 subjects will be randomized to CC-90001 200mg
Drug: CC-90001
Placebo PO QD
Placebo Comparator
55 subjects will be randomized to placebo
Other: Placebo
CC-90001 400 mg PO QD- Sub-Study
Experimental
30 subjects will be randomized to CC-90001 400mg
Drug: CC-90001
Placebo PO QD- Sub-Study
Placebo Comparator
15 subjects will be randomized to placebo
Other: Placebo
Interventions
Name
Type
Description
Arm Group Labels
Other Names
CC-90001
Drug
CC-90001 is a potent, selective inhibitor of JNK.
CC-90001 200 mg PO QD
CC-90001 400 mg PO QD
CC-90001 400 mg PO QD- Sub-Study
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
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 Outcomes
Measure
Description
Time Frame
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
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
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
Participants in the placebo arm during treatment period were re-randomized during the active treatment period to receive either CC-90001 200mg or CC-90001 400mg.
1 participant in the active treatment period did not have the end of study form filled out and therefore was listed in the missing row.
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
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
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
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
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
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)
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)
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)
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)
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:
from baseline to re-randomization (approximately 56 weeks for the IPF cohort and 28 weeks for the PPF cohort)
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)
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
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)
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)
Los Angeles
California
90048
United States
Local Institution - 514
Sacramento
California
95817
United States
University of California Davis Health System
Sacramento
California
95817
United States
Stanford University Pulmonary and Critical Care Clinic
Stanford
California
94305
United States
University of Florida
Gainesville
Florida
32610
United States
University of Miami and Sylvester Cancer Center
Miami
Florida
33136
United States
University of Louisville
Louisville
Kentucky
40202
United States
The Lung and Research Center, LLC
Chesterfield
Missouri
63017
United States
Mt. Sinai School of Medicine
New York
New York
10029
United States
Duke University Health System - Duke Pulmonary Transplant Clinic
Durham
North Carolina
27710
United States
University of Cincinnati Medical Center
Cincinnati
Ohio
45267
United States
University Hospitals Cleveland Medical Center
Cleveland
Ohio
44121
United States
Pulmonary & Sleep Center of Oklahoma
Tulsa
Oklahoma
74137
United States
University of Pittsburgh Medical Center
Pittsburgh
Pennsylvania
15213
United States
Medical University of South Carolina
Charleston
South Carolina
29425
United States
Vanderbilt University Medical Center
Nashville
Tennessee
37212
United States
Baylor University Medical Center
Dallas
Texas
75246
United States
Local Institution - 502
Dallas
Texas
75246
United States
University of Utah Health Care
Salt Lake City
Utah
84132
United States
University of Vermont
Burlington
Vermont
05405
United States
Local Institution - 608
Camperdown
New South Wales
2050
Australia
Royal Prince Alfred Hospital
Camperdown
New South Wales
2050
Australia
Concord Repatriation General Hospital
Concord
New South Wales
2139
Australia
Mater Medical Centre
South Brisbane
Queensland
4101
Australia
Local Institution - 601
Adelaide
South Australia
5000
Australia
Royal Adelaide Hospital
Adelaide
South Australia
5000
Australia
Flinders Medical Centre
Bedford Park
South Australia
5042
Australia
Local Institution - 605
Parkville
Victoria
3050
Australia
Royal Melbourne Hospital
Parkville
Victoria
3050
Australia
Fiona Stanley Hospital
Murdoch
Western Australia
6150
Australia
Institute for Respiratory Health Inc
Nedlands
Western Australia
6009
Australia
St Vincent Hospital - Sydney
Darlinghurst
2010
Australia
Clinica de Pneumologia S/S
Goiânia
Goiás
74110-030
Brazil
Irmandade da Santa Casa de Misericordia de Porto Alegre
Porto Alegre
Rio Grande do Sul
90085-074
Brazil
Hospital Nossa Senhora da Conceicao
Porto Alegre
Rio Grande do Sul
91350-200
Brazil
Hospital Ernesto Dornelles
Porto Alegre
90610-093
Brazil
Universidade Federal do Rio de Janeiro (UFRJ)-Hospital Universitario Clementino Fraga Filho (HUCFF)
Rio de Janeiro
21941
Brazil
Faculdade de Medicina do ABC
Santo André
09060-650
Brazil
Incor - Instituto do Coracao HCFMUSP
São Paulo
01414-001
Brazil
Kelowna & Respiratory Allergy Clinic
Kelowna
British Columbia
V1W 1V3
Canada
Local Institution - 621
Kelowna
British Columbia
V1W 1V3
Canada
Local Institution - 620
Vancouver
British Columbia
V5Z 1M9
Canada
The Lung Centre Respiratory Clinic - Vancouver General Hospital Location
Vancouver
British Columbia
V5Z 1M9
Canada
Dr. Syed Anees Medicine Professional Corporation
Windsor
Ontario
N8X 1T3
Canada
Local Institution - 623
Windsor
Ontario
N8X 1T3
Canada
Centro de Reumatologia y Ortopedia SAS
Barranquilla
080020
Colombia
Local Institution - 631
Bogotá
0
Colombia
Centro Especializado en Enfermedades Pulmonares
Bogotá
Colombia
Centro Medico Imbanaco
Cali
Colombia
Helios Klinikum Emil Von Behring
Berlin
14165
Germany
Ruhrlandklinik University Hospital
Essen
45239
Germany
AGAPLESION EV. KRANKENHAUS MITTELHESSEN gGmbH
Giessen
35398
Germany
Local Institution - 642
Giessen
35398
Germany
Universitatsklinikum Heidelberg
Heidelberg
69120
Germany
Waldburg-Zeil Kliniken -Fachkliniken Wangen
Wangen
88239
Germany
Democritus University of Thrace
Alexandroupoli
68100
Greece
University General Hospital of Alexandroupolis
Alexandroupoli
68100
Greece
University General Hospital Attikon
Haidari
12462
Greece
University of Crete - University General Hospital of Heraklion
Heraklion
711 10
Greece
General Hospital of Heraklion Benizeleio Pananeio
Heraklion
71409
Greece
Spitalul Clinic de Pneumoftiziologie Leon Daniello Cluj Napoca
Cluj-Napoca
Romania
Spitalul Clinic de Boli Infectioase si Pneumoftiziologie Dr. Victor Babes Timisoara
Timișoara
300312
Romania
City clinical hospital No 9
Izhevsk
426063
Russia
Federal State Budgetary Scientific Institution Research Institute for Complex Issues of Cardiovascul
Kemerovo
650002
Russia
TSBIH Territorial Clinical Hospital
Krasnoyarsk
660022
Russia
Russian Academy of Medical Sciences RAMS - Central Scientific Research Institute of Tuberculosis CTR
Moscow
107564
Russia
Federal Medico-Biological Agency FMBA - Federal Research Clinical Center FGUZ Clinical Hospital No.
Moscow
Russia
Local Institution - 666
Nizhny Novgorod
603011
Russia
Nizhny Novgorod Research Institute of Hygiene and Occupational Pathology
Nizhny Novgorod
603011
Russia
Republican Hospital
Petrozavodsk
185019
Russia
FSBHI Clincial Research Institute of Phithisioplulmonoloyg
Saint Petersburg
191036
Russia
Local Institution - 667
Saint Petersburg
191180
Russia
Vvedenskaya Hospital
Saint Petersburg
191180
Russia
Saint-Petersburg State Institution of Healthcare
Saint Petersburg
193312
Russia
Pavlov First Saint Petersburg State Medical University
Saint Petersburg
197022
Russia
Local Institution - 675
Saratov
410053
Russia
Saratov Regional Clinical Hospital
Saratov
410053
Russia
SAIH of Yaroslavl region Clinical Hospital for Emergency Medical Care n.a. N.V.Solovyev
Yaroslavl
150003
Russia
Ural State Medical Academy - Medical Association Novaya Bolnitsa
Yekaterinburg
620109
Russia
Buddhist Dalin Tzu Chi General Hospital
Dalin
62247
Taiwan
Kaohsiung Medical University Hospital
Kaohsiung City
807
Taiwan
China Medical University Hospital
Taichung
40447
Taiwan
National Taiwan University Hospital
Taipei, Zhongzheng Dist.
10002
Taiwan
Ege Universitesi Tip Fakultesi Hastanesi Ege University Medical Faculty Hospital
Bornova
35100
Turkey (Türkiye)
Local Institution - 681
Bornova
35100
Turkey (Türkiye)
Uludag Universitesi Tip Fakultesi
Bursa
16059
Turkey (Türkiye)
Istanbul Universitesi - Cerrahpasa Tip Fakultesi Cerrahpasa Medical Faculty
Istanbul
34098
Turkey (Türkiye)
Izmir Dr.Suat Seren Chest Diseases Hospital
Izmir
35100
Turkey (Türkiye)
Communal Institution Dnipropetrovsk City Clinical Hospital #6 of Dnipropetrovsk Regional Council
Dnipro
49023
Ukraine
Regional Phthisiopulmonological Center
Ivano-Frankivsk
76018
Ukraine
Kharkiv City Clinical Hospital #13
Kharkiv
61124
Ukraine
CI of Healthcare RCH - Center of Medical Emergency and Accident Medicine
Kharkiv
61204
Ukraine
State Institution National Scientific Center of Radiation Medicine of NAMS of Ukraine
Kyiv
03115
Ukraine
SI F.H.Yanovskyi National Institute of Phthisiatry and Pulmonology of Academy of Medical Sciences
Kyiv
03680
Ukraine
Birmingham Chest Clinic
Birmingham
B3 3HX
United Kingdom
Hull and East Yorkshire Hospitals NHS Trust - Castle Hill Hospital
Cottingham
HU16 5JQ
United Kingdom
Hinchingbrooke Hospital
Huntingdon
PE29 6NT
United Kingdom
The Leeds Teaching Hospitals NHS Trust - St James's University Hospital
Leeds
LS9 7TF
United Kingdom
University Hospitals of Leicester NHS Trust - Glenfield Hospital - Institute for Lung Health ILH
Leicester
LE3 9QP
United Kingdom
Aintree University Hospital
Liverpool (Walton Centre)
L9 7LJ
United Kingdom
University Hospital Llandough
Llandough
CF64 2XX
United Kingdom
University College London Hospitals
London
NW1 2PG
United Kingdom
Local Institution - 598
Newcastle
NE1 4LP
United Kingdom
Royal Victoria Infirmary
Newcastle
NE1 4LP
United Kingdom
Local Institution - 697
Norwich
NR4 7UY
United Kingdom
Norfolk and Norwich University Hospital
Norwich
NR4 7UY
United Kingdom
The University of Nottingham - Nottingham Respiratory Research Unit NRRU
Nottingham
NG5 1PB
United Kingdom
Salford Royal
Salford
M6 8HD
United Kingdom
Southampton General Hospital
Southhampton
SO01 6YD
United Kingdom
Local Institution - 694
Westbury-on-Trym/ Bristol
BS10 5NB
United Kingdom
Southmead Hospital
Westbury-on-Trym/ Bristol
BS10 5NB
United Kingdom
Derived
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.
Participants who were in the placebo arm during treatment period and are now taking CC-90001 200mg
FG0000 subjects
FG0010 subjects
FG00215 subjects
FG003
CC-90001 400mg
Participants who were in the placebo arm during treatment period and are now taking CC-90001 400mg
FG0000 subjects
FG0010 subjects
FG00215 subjects
FG003
COMPLETED
FG0005 subjects
FG00113 subjects
FG00215 subjects
FG0033 subjects
FG004
NOT COMPLETED
FG00026 subjects
FG00114 subjects
FG00215 subjects
FG00312 subjects
FG004
Type
Comment
Reasons
Death
FG0002 subjects
FG0011 subjects
FG0021 subjects
FG003
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
CC-90001 200mg (IPF Study)
CC-90001 200mg PO QD
BG001
CC-90001 400mg (IPF Study)
CC-90001 400mg PO QD
BG002
Placebo (IPF Study)
Placebo
BG003
CC-90001 400mg (PPF Sub-Study)
CC-90001 400mg PO QD
BG004
Placebo (PPF Sub-Study)
Placebo
BG005
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00039
BG00137
BG00236
BG00315
BG0048
BG005135
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Categorical
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
<=18 years
BG0000
BG0010
BG0020
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG00011
BG0018
BG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Hispanic or Latino
BG0004
BG0014
BG002
Race (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
American Indian or Alaska Native
BG0000
BG0010
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
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.
Full Analysis Set in IPF Cohort
Posted
Mean
Standard Deviation
Percentage Point
from baseline to week 24
ID
Title
Description
OG000
CC-90001 200mg (IPF Study)
CC-90001 200mg PO QD
OG001
CC-90001 400mg (IPF Study)
CC-90001 400mg PO QD
OG002
Placebo (IPF Study)
Placebo
Units
Counts
Participants
OG00039
OG00137
OG00236
Title
Denominators
Categories
Week 1
ParticipantsOG00038
ParticipantsOG00132
ParticipantsOG00236
Title
Measurements
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.
Full Analysis Set participants with evaluable measures in IPF cohort at week 24
Posted
Mean
Standard Deviation
mL
from baseline to week 24
ID
Title
Description
OG000
CC-90001 200mg (IPF Study)
CC-90001 200mg PO QD
OG001
CC-90001 400mg (IPF Study)
CC-90001 400mg PO QD
OG002
Placebo (IPF Study)
Placebo
Units
Counts
Participants
OG000
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.
Full Analysis Set in the IPF cohort
Posted
Mean
Standard Deviation
meters
From baseline up to week 104
ID
Title
Description
OG000
CC-90001 200mg (IPF Study)
CC-90001 200mg PO QD
OG001
CC-90001 400mg (IPF Study)
CC-90001 400mg PO QD
OG002
Placebo (IPF Study)
Placebo
OG003
Placebo/CC-90001 200mg (IPF Study)
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.
Full Analysis Set in the IPF cohort
Posted
Mean
Standard Deviation
Score on a Scale
From baseline up to week 104
ID
Title
Description
OG000
CC-90001 200mg (IPF Study)
CC-90001 200mg PO QD
OG001
CC-90001 400mg (IPF Study)
CC-90001 400mg PO QD
OG002
Placebo (IPF Study)
Placebo
OG003
Placebo/CC-90001 200mg (IPF Study)
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.
Full analysis set in IPF Cohort
Posted
Number
Percentage of participants
From Baseline up to week 24
ID
Title
Description
OG000
CC-90001 200mg (IPF Study)
CC-90001 200mg PO QD
OG001
CC-90001 400mg (IPF Study)
CC-90001 400mg PO QD
OG002
Placebo (IPF Study)
Placebo
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.
Full analysis set with evaluable SGRQ measures in IPF Cohort
Posted
Mean
Standard Deviation
Score on a Scale
From Baseline up to week 24
ID
Title
Description
OG000
CC-90001 200mg (IPF Study)
CC-90001 200mg PO QD
OG001
CC-90001 400mg (IPF Study)
CC-90001 400mg PO QD
OG002
Placebo (IPF Study)
Placebo
Units
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.
Full analysis set with evaluable UCSD-SOBQ measures in IPF Cohort
Posted
Mean
Standard Deviation
Score on a Scale
From Baseline up to week 24
ID
Title
Description
OG000
CC-90001 200mg (IPF Study)
CC-90001 200mg PO QD
OG001
CC-90001 400mg (IPF Study)
CC-90001 400mg PO QD
OG002
Placebo (IPF Study)
Placebo
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
Re-randomized safety set
Posted
Count of Participants
Participants
From re-randomization to end of treatment (approximately 84 weeks)
ID
Title
Description
OG000
CC-90001 200mg (IPF Study)
CC-90001 200mg PO QD
OG001
CC-90001 400mg (IPF Study)
CC-90001 400mg PO QD
OG002
Placebo/CC-90001 200mg (IPF Study)
Participants who received placebo in the placebo treatment phase and then CC-90001 200mg PO QD in the active treatment extension phase
OG003
Placebo/CC-90001 400mg (IPF Study)
Participants who received placebo in the placebo treatment phase and then CC-90001 400mg PO QD in the active treatment extension phase
OG004
Secondary
Number of Participants With Adverse Events in the Placebo Controlled Period
Number of participants with Adverse events
Safety Set
Posted
Count of Participants
Participants
from baseline to re-randomization (approximately 56 weeks for the IPF cohort and 28 weeks for the PPF cohort)
ID
Title
Description
OG000
CC-90001 200mg (IPF Study)
CC-90001 200mg PO QD
OG001
CC-90001 400mg (IPF Study)
CC-90001 400mg PO QD
OG002
Placebo (IPF Study)
Placebo
OG003
CC-90001 400mg (PPF Sub-Study)
CC-90001 400mg PO QD
OG004
Placebo (PPF Sub-Study)
Placebo
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.
Re-randomized safety set
Posted
Count of Participants
Participants
From re-randomization to end of treatment (approximately 84 weeks)
ID
Title
Description
OG000
CC-90001 200mg (IPF Study)
CC-90001 200mg PO QD
OG001
CC-90001 400mg (IPF Study)
CC-90001 400mg PO QD
OG002
Placebo/CC-90001 200mg (IPF Study)
Participants who received placebo in the placebo treatment phase and then CC-90001 200mg PO QD in the active treatment extension phase
OG003
Placebo/CC-90001 400mg (IPF Study)
Participants who received placebo in the placebo treatment phase and then CC-90001 400mg PO QD in the active treatment extension phase
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.
Safety Set
Posted
Count of Participants
Participants
from baseline to re-randomization (approximately 56 weeks for the IPF cohort and 28 weeks for the PPF cohort)
ID
Title
Description
OG000
CC-90001 200mg (IPF Study)
CC-90001 200mg PO QD
OG001
CC-90001 400mg (IPF Study)
CC-90001 400mg PO QD
OG002
Placebo (IPF Study)
Placebo
OG003
CC-90001 400mg (PPF Sub-Study)
CC-90001 400mg PO QD
OG004
Placebo (PPF Sub-Study)
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:
from baseline to re-randomization (approximately 56 weeks for the IPF cohort and 28 weeks for the PPF cohort)
ID
Title
Description
OG000
CC-90001 200mg (IPF Study)
CC-90001 200mg PO QD
OG001
CC-90001 400mg (IPF Study)
CC-90001 400mg PO QD
OG002
Placebo (IPF Study)
Placebo
OG003
CC-90001 400mg (PPF Sub-Study)
CC-90001 400mg PO QD
OG004
Placebo (PPF Sub-Study)
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
Re-Randomized Safety Set
Posted
Mean
Standard Deviation
msec
From re-randomization to 4 week follow up after end of treatment (approximately 84 weeks)
ID
Title
Description
OG000
CC-90001 200mg (IPF Study)
CC-90001 200mg PO QD
OG001
CC-90001 400mg (IPF Study)
CC-90001 400mg PO QD
OG002
Placebo/CC-90001 200mg (IPF Study)
Participants who received placebo in the placebo treatment phase and then CC-90001 200mg PO QD in the active treatment extension phase
OG003
Placebo/CC-90001 400mg (IPF Study)
Participants who received placebo in the placebo treatment phase and then CC-90001 400mg PO QD in the active treatment extension phase
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
Safety Set
Posted
Mean
Standard Deviation
msec
from baseline to week 24
ID
Title
Description
OG000
CC-90001 200mg (IPF Study)
CC-90001 200mg PO QD
OG001
CC-90001 400mg (IPF Study)
CC-90001 400mg PO QD
OG002
Placebo (IPF Study)
Placebo
OG003
CC-90001 400mg (PPF Sub-Study)
CC-90001 400mg PO QD
OG004
Placebo (PPF Sub-Study)
Placebo
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.
Re-Randomized Safety Set
Posted
Count of Participants
Participants
From re-randomization to 4 week follow up after end of treatment (approximately 84 weeks)
ID
Title
Description
OG000
CC-90001 200mg (IPF Study)
CC-90001 200mg PO QD
OG001
CC-90001 400mg (IPF Study)
CC-90001 400mg PO QD
OG002
Placebo/CC-90001 200mg (IPF Study)
Participants who received placebo in the placebo treatment phase and then CC-90001 200mg PO QD in the active treatment extension phase
OG003
Placebo/CC-90001 400mg (IPF Study)
Participants who received placebo in the placebo treatment phase and then CC-90001 400mg PO QD in the active treatment extension phase
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.
Safety Set
Posted
Count of Participants
Participants
from baseline to re-randomization (approximately 56 weeks for the IPF cohort and 28 weeks for the PPF cohort)
ID
Title
Description
OG000
CC-90001 200mg (IPF Study)
CC-90001 200mg PO QD
OG001
CC-90001 400mg (IPF Study)
CC-90001 400mg PO QD
OG002
Placebo (IPF Study)
Placebo
OG003
CC-90001 400mg (PPF Sub-Study)
CC-90001 400mg PO QD
OG004
Placebo (PPF Sub-Study)
Placebo
Time Frame
Adverse Events and Serious Adverse Events: (From first dose to last dose + 28 days): Approximately 84 weeks All-Cause mortality (From randomization to end of study): Approximately 104 weeks
Description
The number at Risk for All-Cause Mortality represents all Randomized Participants.
The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
CC-90001 200mg IPF Study
CC-90001 200mg PO QD
5
39
16
39
32
39
EG001
CC-90001 400mg IPF Study
CC-90001 400mg PO QD
5
37
9
37
33
37
EG002
Placebo IPF Study
Placebo
2
36
2
36
31
36
EG003
Active Treatment Phase CC-90001 200mg Following Placebo IPF Study
CC-90001 200mg PO QD
2
15
3
15
10
15
EG004
Active Treatment Phase CC-90001 400mg Following Placebo IPF Study
CC-90001 400mg PO QD
2
15
4
15
13
15
EG005
CC-90001 400mg PPF Sub-Study
CC-90001 400mg PO QD
1
15
3
15
12
15
EG006
Placebo PPF Sub-Study
Placebo
0
8
0
8
1
8
EG007
Active Treatment Phase CC-90001 200mg Following Placebo PPF Sub-Study
CC-90001 200mg PO QD
0
3
0
3
2
3
EG008
Active Treatment Phase CC-90001 400mg Following Placebo PPF Sub-Study
CC-90001 400mg PO QD
0
3
0
3
3
3
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Neutropenia
Blood and lymphatic system disorders
MedDRA 24.1
Systematic Assessment
EG0001 affected39 at risk
EG0010 affected37 at risk
EG0020 affected36 at risk
EG0030 affected15 at risk
EG0040 affected15 at risk
EG0050 affected15 at risk
EG0060 affected8 at risk
EG0070 affected3 at risk
EG0080 affected3 at risk
Acute coronary syndrome
Cardiac disorders
MedDRA 24.1
Systematic Assessment
EG0000 affected39 at risk
EG0011 affected37 at risk
EG0020 affected36 at risk
EG003
Acute myocardial infarction
Cardiac disorders
MedDRA 24.1
Systematic Assessment
EG0000 affected39 at risk
EG0011 affected37 at risk
EG0020 affected36 at risk
EG003
Angina pectoris
Cardiac disorders
MedDRA 24.1
Systematic Assessment
EG0001 affected39 at risk
EG0010 affected37 at risk
EG0020 affected36 at risk
EG003
Obstructive pancreatitis
Gastrointestinal disorders
MedDRA 24.1
Systematic Assessment
EG0001 affected39 at risk
EG0010 affected37 at risk
EG0020 affected36 at risk
EG003
Pancreatitis acute
Gastrointestinal disorders
MedDRA 24.1
Systematic Assessment
EG0000 affected39 at risk
EG0011 affected37 at risk
EG0020 affected36 at risk
EG003
Salivary hypersecretion
Gastrointestinal disorders
MedDRA 24.1
Systematic Assessment
EG0000 affected39 at risk
EG0011 affected37 at risk
EG0020 affected36 at risk
EG003
Multiple organ dysfunction syndrome
General disorders
MedDRA 24.1
Systematic Assessment
EG0000 affected39 at risk
EG0010 affected37 at risk
EG0021 affected36 at risk
EG003
Non-cardiac chest pain
General disorders
MedDRA 24.1
Systematic Assessment
EG0000 affected39 at risk
EG0010 affected37 at risk
EG0020 affected36 at risk
EG003
Drug-induced liver injury
Hepatobiliary disorders
MedDRA 24.1
Systematic Assessment
EG0001 affected39 at risk
EG0010 affected37 at risk
EG0020 affected36 at risk
EG003
Atypical pneumonia
Infections and infestations
MedDRA 24.1
Systematic Assessment
EG0001 affected39 at risk
EG0010 affected37 at risk
EG0020 affected36 at risk
EG003
Bronchitis
Infections and infestations
MedDRA 24.1
Systematic Assessment
EG0000 affected39 at risk
EG0011 affected37 at risk
EG0020 affected36 at risk
EG003
COVID-19
Infections and infestations
MedDRA 24.1
Systematic Assessment
EG0001 affected39 at risk
EG0010 affected37 at risk
EG0020 affected36 at risk
EG003
COVID-19 pneumonia
Infections and infestations
MedDRA 24.1
Systematic Assessment
EG0000 affected39 at risk
EG0010 affected37 at risk
EG0020 affected36 at risk
EG003
Diverticulitis
Infections and infestations
MedDRA 24.1
Systematic Assessment
EG0000 affected39 at risk
EG0011 affected37 at risk
EG0020 affected36 at risk
EG003
Haemophilus infection
Infections and infestations
MedDRA 24.1
Systematic Assessment
EG0001 affected39 at risk
EG0010 affected37 at risk
EG0020 affected36 at risk
EG003
Lower respiratory tract infection
Infections and infestations
MedDRA 24.1
Systematic Assessment
EG0000 affected39 at risk
EG0011 affected37 at risk
EG0020 affected36 at risk
EG003
Pneumonia
Infections and infestations
MedDRA 24.1
Systematic Assessment
EG0001 affected39 at risk
EG0011 affected37 at risk
EG0020 affected36 at risk
EG003
Pneumonia aspiration
Infections and infestations
MedDRA 24.1
Systematic Assessment
EG0001 affected39 at risk
EG0010 affected37 at risk
EG0020 affected36 at risk
EG003
Pneumonia bacterial
Infections and infestations
MedDRA 24.1
Systematic Assessment
EG0000 affected39 at risk
EG0011 affected37 at risk
EG0020 affected36 at risk
EG003
Suspected COVID-19
Infections and infestations
MedDRA 24.1
Systematic Assessment
EG0001 affected39 at risk
EG0010 affected37 at risk
EG0020 affected36 at risk
EG003
Subdural haematoma
Injury, poisoning and procedural complications
MedDRA 24.1
Systematic Assessment
EG0000 affected39 at risk
EG0010 affected37 at risk
EG0021 affected36 at risk
EG003
Troponin increased
Investigations
MedDRA 24.1
Systematic Assessment
EG0000 affected39 at risk
EG0010 affected37 at risk
EG0020 affected36 at risk
EG003
Adenocarcinoma gastric
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 24.1
Systematic Assessment
EG0001 affected39 at risk
EG0010 affected37 at risk
EG0020 affected36 at risk
EG003
Chronic myeloid leukaemia
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 24.1
Systematic Assessment
EG0001 affected39 at risk
EG0010 affected37 at risk
EG0020 affected36 at risk
EG003
Lung neoplasm malignant
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 24.1
Systematic Assessment
EG0000 affected39 at risk
EG0010 affected37 at risk
EG0020 affected36 at risk
EG003
Pancreatic carcinoma metastatic
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 24.1
Systematic Assessment
EG0001 affected39 at risk
EG0010 affected37 at risk
EG0020 affected36 at risk
EG003
Transitional cell carcinoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)