IDIOPATHIC PULMONARY FIBROSIS

Primary Objective To evaluate the effect of CC-90001, 200 mg and 400 mg, when orally administered (PO) once daily (QD), compared with placebo, on percent of predicted forced vital capacity (FVC) after 24 weeks of treatment in subjects with IPF. Secondary Objectives To evaluate the effects of CC-90001, 200 mg and 400 mg PO QD, compared to placebo, after 24 weeks of treatment in subjects with IPF, on:  FVC (milliliters [mL])  Six-minute Walk Test (6MWT)  Disease progression  Heath-related quality of life: St. George’s Respiratory Questionnaire (SGRQ) and University of California San Diego-Shortness of Breath Questionnaire (UCSDSOBQ)  Dose response  Safety and tolerability

CC-90001-IPF-001

CC- 90001

Tablet

200

Primary Outcome Measures :
Percentage point change in % predicted Forced vital capacity (FVC) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Up to approximately 104 weeks ]
Change in the distance walked during the 6MWT as measured in meters (m)

Disease Progression [ Time Frame: Up to approximately 24 weeks ]
Time to disease progression

Quality of Life - Saint George's Respiratory [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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?

Inclusion Criteria
Subjects must satisfy the following criteria to be enrolled in the study:
1. Subject is male or female ≥ 40 years of age at the time of signing the informed consent form (ICF)
2. Subject must understand and voluntarily sign an ICF prior to any study-related
assessments/procedures being conducted
3. Subject is willing and able to adhere to the study visit schedule and other protocol requirements
4. Subject was diagnosed with IPF within 4 years of Screening, according to the most recent
IPF guidelines (Raghu, 2011) for diagnosis and management
5. Diagnosis of IPF is supported by HRCT and historical surgical lung biopsy (SLB) as
outlined below and in Appendix F. (Note: HRCT scan performed within 12 months of
randomization may be used if it meets image acquisition guidelines and scan is reviewed by centralized review)
6. Extent of fibrotic changes (eg, honeycombing, reticular changes) greater than the extent
of emphysema on HRCT scan, as determined by central review
7. No features supporting an alternative diagnosis on transbronchial biopsy, bronchoalveolar
lavage (BAL), or SLB, if performed
8. Percent predicted forced vital capacity (% FVC) ≥ 45% at Screening confirmed by central review
9. Change in FVC (measured in milliliters [mL]) between Screening and Day 1 less than a
10% relative difference, calculated as: the absolute value of 100% * (Screening FVC
[mL] - Day 1 FVC [mL]) / Screening FVC (mL)
10. Percent predicted diffusion capacity of the lung for carbon monoxide (DLCO) ≥ 30% and
≤ 85% predicted at Screening
11. Able to walk ≥ 150 meters during the 6-minute walk test (6MWT) at Screening
12. Females of childbearing potential (FCBP) must:
a. Have two negative pregnancy tests as verified by the Investigator prior to starting IP.
She must agree to ongoing pregnancy testing during the course of the study, and after
end of study treatment. This applies even if the subject practices true abstinence*
from heterosexual contact
b. Either commit to true abstinence* from heterosexual contact (which must be reviewed
on a monthly basis and source documented) or agree to use two effective birth control
methods (for example: birth control pills, condoms, etc) at the same time, and be able
to comply with, effective contraception without interruption, 28 days prior to starting
IP, during the study therapy (including dose interruptions), and for 28 days after discontinuation of IP
13. Male subjects must:
a. Practice true abstinence* (which must be reviewed on a monthly basis) or agree to
use condoms not made out of natural [animal] membrane during sexual contact with a
pregnant female or a female of childbearing potential while participating in the study,
during dose interruptions and for at least 28 days following IP discontinuation, even if
he has undergone a successful vasectomy

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 has any condition including the presence of laboratory abnormalities, which
places the subject at unacceptable risk if he/she were to participate in the study
3. Subject has any condition that confounds the ability to interpret data from the study
4. Significant clinical worsening of IPF between Screening and Baseline (Day 1), in the
opinion of the Investigator
5. Subjects with any of the following laboratory criteria:
 White blood cell count (WBC) < 3500/mm3 (< 3.5 X 109 /L) or > 14,000/mm3 (> 14 X 109 /L)
 Platelet count < 120,000/μL (< 120 X 109 /L)
 Serum creatinine > 1.5 mg/dL (> 132.6 μmol/L)
 Aspartate aminotransferase (AST/SGOT) > 1.5 X upper limit of normal (ULN)
 Alanine aminotransferase (ALT/SGPT) > 1.5 X upper limit of normal (ULN)
 Total bilirubin > 2 mg/dL (> 34.2 µmol/L)
 Hemoglobin < 10 g/dL (< 100 g/L)
6. Subject with a QTcF > 450 msec
7. Any condition other than IPF that in the opinion of the Investigator is likely to result in
the death of the subject within the next year
8. Inability to obtain reproducible, high-quality pulmonary function tests.
9. Evidence of clinically relevant airways obstruction (ie, FEV1/FVC < 0.7) at Screening
and/or significant respiratory disorder/pathology (eg, pulmonary arterial hypertension,
asthma, tuberculosis, sarcoidosis, hypersensitivity pneumonitis, aspergillosis, asbestosis,
neoplastic disease, cystic fibrosis or other interstitial lung disease) other than IPF.
10. Subject is likely to have lung transplantation during the study (being on transplantation
list is acceptable for participation)
11. Impairment (other than dyspnea) limiting the ability to comply with study requirements
(eg, pulmonary function tests, 6-minute walk test)
12. Subjects using any therapy targeted to treat IPF including, but not limited to, pirfenidone,
nintedanib, endothelium receptor antagonists (eg, bosentan, ambrisentan), interferon
gamma-1b, imatinib mesylate, N-acetylcysteine, azathioprine, cyclophosphamide,
methotrexate and cyclosporine, inhaled and oral steroids (eg, prednisone > 12.5 mg/day
or equivalent) and oral anticoagulants within 4 weeks of the Screening Visit. (Note: Oral
anticoagulants for conditions other than IPF are permitted. Subjects should not
discontinue any of these therapies for the sole purpose of participating in this study.)
13. Use of any cytokine modulators, such as etanercept, adalimumab, efalizumab, infliximab
or rituximab within 12 weeks of randomization or alefacept within 24 months of randomization
14. Use of an inhaled long-acting bronchodilator within 24 hours of the Screening Visit or
short-acting bronchodilator within 8 hours of the Screening Visit
15. Use of ≥ 15 hours of supplemental oxygen per day or resting arterial oxygen saturation
by pulse oximetry (SpO2) of < 92% (room air at sea level) or resting SpO2 of < 88%
(room air at ≥ 5000 feet [1524 meters] above sea level)
16. Use of drugs that are known to cause hepatotoxicity, such as, but not limited to,
acetaminophen (paracetamol) at dosages of > 3 grams/day and niacin dosage of > 2
grams/day while on study or within 2 weeks of first dose of IP
17. Use of any medications that are substrates of one or more of the transporters P-gp, BCRP,
OAT3, OATP1B1, OATP1B3, and OCT2 and have a narrow therapeutic index (eg, digoxin)
18. History of recent (within 6 months of Screening) deep vein thrombosis (DVT) or
pulmonary embolism (PE) and/or recurrent DVT or recurrent PE
19. History of artificial valve replacement requiring chronic anticoagulation
20. History of congenital and/or acquired immunodeficiencies (eg, common variable
immunodeficiency, human immunodeficiency virus [HIV], etc)
21. History of hepatitis B and/or hepatitis C
22. Active or history of recurrent bacterial, viral, fungal, mycobacterial or other infections
(including, but not limited to, atypical mycobacterial disease and herpes zoster), or any
major episode of infection requiring hospitalization or treatment with intravenous or oral
antibiotics within 4 weeks of the Screening Visit and at any time during the Screening
Phase, up through the first dose of IP
23. History of latent or active TB, unless there is medical record documentation of successful
completion of a standard course of treatment
24. Clinical diagnosis of any connective tissue disease, including, but not limited to,
scleroderma, polymyositis/dermatomyositis, systemic lupus erythematosus, and rheumatoid arthritis
25. History of end-stage renal disease requiring dialysis
26. History of severe hepatic impairment or end-stage liver disease
27. History of Gilbert’s syndrome
28. History of alcohol or drug abuse within 6 months prior to Screening
29. Cigarette smoking within 3 months of Screening or unwillingness to avoid tobacco
products throughout the study
30. History of malignancy (exceptions: excised and cured basal/squamous cell skin
carcinomas) and cervical carcinoma in situ with no recurrence in 5 years
31. Pregnancy or lactation
32. Use of any investigational drug within one month of Screening, or 5 PD/PK half-lives (whichever is longer)