Investigation to Efficacy and Safety of CC-90001 in patients with Idiopathic Pulmonary Fibrosis

Phase 1

Conditions: IDIOPATHIC PULMONARY FIBROSIS
MedDRA version: 20.0Level: LLTClassification code 10067761Term: Exacerbation of idiopathic pulmonary fibrosisSystem Organ Class: 100000004855
Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Registration Number: EUCTR2016-003473-17-GB

Lead Sponsor: Celgene Corporation

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 135

Inclusion Criteria

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. Investigator has considered all available IPF treatment options with
the potential subject before consenting the subject for participation in
the study
5. Diagnosis of IPF is supported by HRCT as described in the Protocol
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.Hemoglobin-corrected percent predicted diffusion capacity of the lung
for carbon monoxide (DLCO) = 25% and = 85% predicted at Screening
11. Able to walk = 150 meters during the 6-minute walk test (6MWT) at
Screening
12. Investigator has considered all available IPF treatment options with
the potential subject before consenting the subject for participation in
the study
Females of childbearing potential (FCBP) 1 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.
[refer to protocol]
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 (one of which is highly
effective) 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 [Refer to protocol]
13. Male subjects must:
Practice true abstinence (which must be reviewed on a monthly basis) or
agree to use a latex condom or nonlatex condom not made out of natural
(animal) membrane (eg, polyurethane) 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.
14. For subjects stratified to the protocol-allowable standard of care
therapy group (only): Subjects must be receiving and agree to maintain
the same dose of protocol-allowable standard of care (SOC) therapy for
at least 8 weeks prior to Screening Visit 1 and must agree to continue
this dose through Visit 9/Week 24. Adjustments in pirfenidone dose
after randomization (Visit 2) may be allowed for safety or tolerability
reasons, according
to the pirfenidone label.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 62
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 148

Exclusion Criteria

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
(Visit 2), 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 requiring treatment, 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 first 24
weeks of 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 the following medications: nintedanib, endothelium
receptor antagonists (eg, bosentan, ambrisentan), interferon gamma-1b,
imatinib mesylate, N-acetylcysteine, azathioprine, cyclophosphamide,
methotrexate, mycophenolate mofetil, cyclosporine, and oral steroids
(eg, prednisone > 12.5 mg/day or equivalent) within 4 weeks prior to
the Screening Visit. (Note: Refer to protocol.)
13. Use of any cytokine modulator/biologic, such as etanercept,
adalimumab, efalizumab, infliximab, or rituximab within 12 weeks 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 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
16. 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, mycophenolate mofetil)
17. History of recent (within 6 months of Screening) deep vein
thrombosis (DVT) or pulmonary embolism (PE) and/or recurrent DVT or
recurrent PE
18. History of cardiac valve replacement requiring chronic
anticoagulation therapy
19. History of congenital and/or acquired immunodeficiencies (eg,
common variable immunodeficiency, human immunodeficiency virus
[HIV], etc)
20. History of hepatitis B and/or hepatitis C, including those consider

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the effect of CC-90001, 200 mg and 400 mg, when orally administered (PO) once<br>daily (QD), compared with placebo, on percent of predicted forced vital capacity (FVC) after<br>24 weeks of treatment in subjects with IPF.;Secondary Objective: 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:<br>- FVC (milliliters [mL])<br>- Six-minute Walk Test (6MWT)<br>- Disease progression<br>- Heath-related quality of life: St. George’s Respiratory Questionnaire (SGRQ) and University of California San Diego-Shortness of Breath Questionnaire (UCSDSOBQ)<br>- Dose response<br>- Safety and tolerability;Primary end point(s): Forced vital capacity (FVC) - Percentage point difference in % predicted FVC;Timepoint(s) of evaluation of this end point: Baseline to Week 24

Secondary Outcome Measures

Name	Time	Method

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