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

Sponsor

Celgene (Industry)

Overall Status

Completed

CT.gov ID

NCT03142191

Collaborator

(none)

138

Enrollment

Locations

Arms

Actual Duration (Months)

1.5

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Idiopathic Pulmonary Fibrosis Fibrosis Idiopathic Interstitial Pneumonias Pathologic Processes Lung Diseases, Interstitial Lung Diseases Respiratory Tract Diseases	Drug: CC-90001 Other: Placebo	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

138 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jul 26, 2017

Actual Primary Completion Date :

Dec 24, 2021

Actual Study Completion Date :

Dec 24, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CC-90001 400 mg PO QD 55 subjects will be randomized to CC-90001 400mg	Drug: CC-90001 CC-90001 is a potent, selective inhibitor of JNK.
Experimental: CC-90001 200 mg PO QD 55 subjects will be randomized to CC-90001 200mg	Drug: CC-90001 CC-90001 is a potent, selective inhibitor of JNK.
Placebo Comparator: Placebo PO QD 55 subjects will be randomized to placebo	Other: Placebo Placebo
Experimental: CC-90001 400 mg PO QD- Sub-Study 30 subjects will be randomized to CC-90001 400mg	Drug: CC-90001 CC-90001 is a potent, selective inhibitor of JNK.
Placebo Comparator: Placebo PO QD- Sub-Study 15 subjects will be randomized to placebo	Other: Placebo Placebo

Outcome Measures

Primary Outcome Measures

Percentage point change in % predicted Forced vital capacity (FVC) [Up to approximately 24 weeks]
Mean change from Baseline of percent predicted FVC value between either active treatment group and the placebo group.

Secondary Outcome Measures

Absolute change and rate of decline in FVC [Up to approximately 24 weeks]
Absolute change and rate of decline in FVC (expressed in mL) from baseline through Week 24
6-minute Walk Test (6MWT) with Borg Scale [Up to approximately 104 weeks]
Change in the distance walked during the 6MWT as measured in meters (m)
Disease Progression [Up to approximately 24 weeks]
Time to disease progression
Quality of Life - Saint George's Respiratory [Up to approximately 24 weeks]
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.
Quality of life- University of California San Diego Shortness of Breath Questionnaire (UCSD- SOBQ) [Up to approximately 24 weeks]
The UCSD-SOBQ is a 24-item dyspnea questionnaire that asks subjects 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).
Adverse Events (AEs) [Up to Week 108]
Type, frequency, severity, and relationship of AEs, clinical laboratory tests including urine cytology, 12-lead ECG, vital signs, and physical examination
Borg Scale [Up to approximately 104 weeks]
This is a scale that asks you to rate the difficulty of your breathing. It starts at number 0 where your breathing is causing you no difficulty at all and progresses through to number 10 where your breathing difficulty is maximal. How much difficulty is your breathing causing you right now?

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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
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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Loma Linda Univ Medical Center	Loma Linda	California	United States	92354
2	Cedars Sinai Medical Center Rheumatology	Los Angeles	California	United States	90048
3	University of California Davis Health System	Sacramento	California	United States	95817
4	Stanford University Pulmonary and Critical Care Clinic	Stanford	California	United States	94305
5	University of Florida	Gainesville	Florida	United States	32610
6	University of Miami and Sylvester Cancer Center	Miami	Florida	United States	33136
7	University of Louisville	Louisville	Kentucky	United States	40202
8	The Lung and Research Center, LLC	Chesterfield	Missouri	United States	63017
9	Mt. Sinai School of Medicine	New York	New York	United States	10029
10	Duke University Health System - Duke Pulmonary Transplant Clinic	Durham	North Carolina	United States	27710
11	University of Cincinnati Medical Center	Cincinnati	Ohio	United States	45267
12	University Hospitals Cleveland Medical Center	Cleveland	Ohio	United States	44121
13	Pulmonary & Sleep Center of Oklahoma	Tulsa	Oklahoma	United States	74137
14	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania	United States	15213
15	Medical University of South Carolina	Charleston	South Carolina	United States	29425
16	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37212
17	Baylor University Medical Center	Dallas	Texas	United States	75246
18	University of Utah Health Care	Salt Lake City	Utah	United States	84132
19	University of Vermont	Burlington	Vermont	United States	05405
20	Royal Prince Alfred Hospital	Camperdown	New South Wales	Australia	2050
21	Concord Repatriation General Hospital	Concord	New South Wales	Australia	2139
22	Mater Medical Centre	South Brisbane	Queensland	Australia	4101
23	Royal Adelaide Hospital	Adelaide	South Australia	Australia	5000
24	Flinders Medical Centre	Bedford Park	South Australia	Australia	5042
25	Royal Melbourne Hospital	Parkville	Victoria	Australia	3050
26	Fiona Stanley Hospital	Murdoch	Western Australia	Australia	6150
27	Institute for Respiratory Health Inc	Nedlands	Western Australia	Australia	6009
28	St Vincent Hospital - Sydney	Darlinghurst		Australia	2010
29	Clinica de Pneumologia S/S	Goiania	Goiás	Brazil	74110-030
30	Irmandade da Santa Casa de Misericordia de Porto Alegre	Porto Alegre	Rio Grande Do Sul	Brazil	90085-074
31	Hospital Nossa Senhora da Conceicao	Porto Alegre	Rio Grande Do Sul	Brazil	91350-200
32	Hospital Ernesto Dornelles	Porto Alegre		Brazil	90610-093
33	Universidade Federal do Rio de Janeiro (UFRJ)-Hospital Universitario Clementino Fraga Filho (HUCFF)	Rio de Janeiro		Brazil	21941
34	Faculdade de Medicina do ABC	Santo Andre		Brazil	09060-650
35	Incor - Instituto do Coracao HCFMUSP	Sao Paulo		Brazil	01414-001
36	Kelowna & Respiratory Allergy Clinic	Kelowna	British Columbia	Canada	V1W 1V3
37	The Lung Centre Respiratory Clinic - Vancouver General Hospital Location	Vancouver	British Columbia	Canada	V5Z 1M9
38	Dr. Syed Anees Medicine Professional Corporation	Windsor	Ontario	Canada	N8X 1T3
39	Centro de Reumatologia y Ortopedia SAS	Barranquilla		Colombia	080020
40	Centro Especializado en Enfermedades Pulmonares	Bogotá		Colombia
41	Centro Medico Imbanaco	Cali		Colombia
42	Helios Klinikum Emil Von Behring	Berlin		Germany	14165
43	Ruhrlandklinik University Hospital	Essen		Germany	45239
44	AGAPLESION EV. KRANKENHAUS MITTELHESSEN gGmbH	Giessen		Germany	35398
45	Universitatsklinikum Heidelberg	Heidelberg		Germany	69120
46	Waldburg-Zeil Kliniken -Fachkliniken Wangen	Wangen Im Allgaeu		Germany	88239
47	Democritus University of Thrace	Alexandroupolis		Greece	68100
48	University General Hospital of Alexandroupolis	Alexandroupolis		Greece	68100
49	University General Hospital Attikon	Haidari		Greece	12462
50	General Hospital of Heraklion Benizeleio Pananeio	Heraklion		Greece	71409
51	University of Crete - University General Hospital of Heraklion	Iraklio		Greece	711 10
52	Spitalul Clinic de Pneumoftiziologie Leon Daniello Cluj Napoca	Cluj-Napoca		Romania
53	Spitalul Clinic de Boli Infectioase si Pneumoftiziologie Dr. Victor Babes Timisoara	Timisoara		Romania	300312
54	Ural State Medical Academy - Medical Association Novaya Bolnitsa	Ekaterinburg		Russian Federation	620109
55	City clinical hospital No 9	Izhevsk		Russian Federation	426063
56	Federal State Budgetary Scientific Institution Research Institute for Complex Issues of Cardiovascul	Kemerovo		Russian Federation	650002
57	TSBIH Territorial Clinical Hospital	Krasnoyarsk		Russian Federation	660022
58	Russian Academy of Medical Sciences RAMS - Central Scientific Research Institute of Tuberculosis CTR	Moscow		Russian Federation	107564
59	Federal Medico-Biological Agency FMBA - Federal Research Clinical Center FGUZ Clinical Hospital No.	Moscow		Russian Federation
60	Nizhny Novgorod Research Institute of Hygiene and Occupational Pathology	Nizhny Novgorod		Russian Federation	603011
61	Republican Hospital	Petrozavodsk		Russian Federation	185019
62	FSBHI Clincial Research Institute of Phithisioplulmonoloyg	Saint Petersburg		Russian Federation	191036
63	Pavlov First Saint Petersburg State Medical University	Saint-Petersburg		Russian Federation	197022
64	Saratov Regional Clinical Hospital	Saratov		Russian Federation	410053
65	Vvedenskaya Hospital	St. Petersburg		Russian Federation	191180
66	Saint-Petersburg State Institution of Healthcare	St. Petersburg		Russian Federation	193312
67	SAIH of Yaroslavl region Clinical Hospital for Emergency Medical Care n.a. N.V.Solovyev	Yaroslavl		Russian Federation	150003
68	Buddhist Dalin Tzu Chi General Hospital	Dalin		Taiwan	62247
69	Kaohsiung Medical University Hospital	Kaohsiung		Taiwan	807
70	China Medical University Hospital	Taichung City		Taiwan	40447
71	National Taiwan University Hospital	Taipei, Zhongzheng Dist.		Taiwan	10002
72	Ege Universitesi Tip Fakultesi Hastanesi Ege University Medical Faculty Hospital	Bornova		Turkey	35100
73	Uludag Universitesi Tip Fakultesi	Bursa		Turkey	16059
74	Istanbul Universitesi - Cerrahpasa Tip Fakultesi Cerrahpasa Medical Faculty	Istanbul		Turkey	34098
75	Izmir Dr.Suat Seren Chest Diseases Hospital	Izmir		Turkey	35100
76	Communal Institution Dnipropetrovsk City Clinical Hospital #6 of Dnipropetrovsk Regional Council	Dnipro		Ukraine	49023
77	Regional Phthisiopulmonological Center	Ivano-Frankivsk		Ukraine	76018
78	Kharkiv City Clinical Hospital #13	Kharkiv		Ukraine	61124
79	CI of Healthcare RCH - Center of Medical Emergency and Accident Medicine	Kharkiv		Ukraine	61204
80	State Institution National Scientific Center of Radiation Medicine of NAMS of Ukraine	Kyiv		Ukraine	03115
81	SI F.H.Yanovskyi National Institute of Phthisiatry and Pulmonology of Academy of Medical Sciences	Kyiv		Ukraine	03680
82	Birmingham Chest Clinic	Birmingham		United Kingdom	B3 3HX
83	Hull and East Yorkshire Hospitals NHS Trust - Castle Hill Hospital	Cottingham		United Kingdom	HU16 5JQ
84	Hinchingbrooke Hospital	Huntingdon		United Kingdom	PE29 6NT
85	The Leeds Teaching Hospitals NHS Trust - St James's University Hospital	Leeds		United Kingdom	LS9 7TF
86	University Hospitals of Leicester NHS Trust - Glenfield Hospital - Institute for Lung Health ILH	Leicester		United Kingdom	LE3 9QP
87	Aintree University Hospital	Liverpool (Walton Centre)		United Kingdom	L9 7LJ
88	University Hospital Llandough	Llandough		United Kingdom	CF64 2XX
89	University College London Hospitals	London		United Kingdom	NW1 2PG
90	Royal Victoria Infirmary	Newcastle		United Kingdom	NE1 4LP
91	Norfolk and Norwich University Hospital	Norwich		United Kingdom	NR4 7UY
92	The University of Nottingham - Nottingham Respiratory Research Unit NRRU	Nottingham		United Kingdom	NG5 1PB
93	Salford Royal	Salford		United Kingdom	M6 8HD
94	Southampton General Hospital	Southhampton		United Kingdom	SO01 6YD
95	Southmead Hospital	Westbury-on-Trym/ Bristol		United Kingdom	BS10 5NB