Trial from ClinicalTrials.gov

For full trial details, please see the original record at



Trial ID
NCT02289417
Ethics application status
Date submitted
10/11/2014
Date registered
10/11/2014
Date last updated
31/08/2017

Titles & IDs
Public title
Efficacy and Safety Study of Apremilast to Treat Active Ulcerative Colitis
Scientific title
A Phase 2, Randomized, Placebo-controlled, Multicenter Study to Investigate the Efficacy and Safety of Apremilast (CC-10004) for Treatment of Subjects With Active Ulcerative Colitis
Secondary ID [1] 0 0
2014-002981-64
Secondary ID [2] 0 0
CC-10004-UC-001
Universal Trial Number (UTN)
Trial acronym
UC
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ulcerative Colitis 0 0
Condition category
Condition code
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders
Oral and Gastrointestinal 0 0 0 0
Inflammatory bowel disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: drugs - Apremilast
Treatment: drugs - Placebo

Experimental: Apremilast 30 mg PO BID - Apremilast 30 mg by mouth (PO) twice a day (BID) for 12 weeks .
After 12 weeks:
Subjects who achieve at least a 20% decrease from baseline in the TMS will continue to receive apremilast 30 mg BID for an additional 40 weeks. (Wk 52)
Subjects who do not achieve at least a 20% decrease from baseline in the TMS will receive apremilast 40 mg BID for an additional 40 weeks (Wk 52).
After 52 weeks, subjects who are eligible for the Extension Phase will continue to receive the same dose of apremilast assigned at Wk 12 (30 mg BID or 40 mg BID) for an additional 52 weeks (Wk 104)

Experimental: Apremilast 40 mg PO BID - Apremilast 40 mg by mouth (PO) twice a day (BID) for 12 weeks.
After 12 weeks, subjects assigned to the 40 mg BID dose of apremilast at baseline will continue to receive apremilast 40 mg BID for an additional 40 weeks (Wk 52).
After 52 weeks, subjects who are eligible for the Extension Phase will continue to receive apremilast 40 mg BID for an additional 52 weeks (Wk 104)

Placebo Comparator: Placebo BID - Identically matching placebo by mouth (PO) twice a day (BID) for 12 weeks. After 12 weeks all subjects randomized to placebo at baseline will be re-randomized to receive apremilast 30 mg or 40 mg BID for an additional 40 weeks (Wk 52).
After Wk 52, subjects who are eligible for the Extension Phase will continue to to receive the same dose of apremilast assigned at Wk 12 (30 mg BID or 40 mg BID) for an additional 52 weeks (Wk 104)


Treatment: drugs: Apremilast


Treatment: drugs: Placebo


Intervention code [1] 0 0
Treatment: drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Proportion of subjects achieving a clinical remission in - Clinical remission is defined as TMS = 2 points, with no individual subscore exceeding 1 point. The TMS is a widely accepted standard for the evaluation of patients with UC and is commonly used as an endpoint in clinical trials. It consists of 4 subscores, each graded from 0 to 3 with higher scores indicating more severe disease:
Stool Frequency Subscore (SFS)
Rectal Bleeding Subscore (RBS)
Endoscopy Subscore
Physician's Global Assessment (PGA)
Timepoint [1] 0 0
Week 12
Secondary outcome [1] 0 0
The proportion of subjects achieving clinical response at Week 12 - : Clinical Response is defined as a decrease from baseline in the TMS of at least 3 points and at least 30%, along with a reduction in the rectal bleeding subscore (RBS) of at least 1 point or an absolute RBS of = 1
Timepoint [1] 0 0
Week 12
Secondary outcome [2] 0 0
The proportion of subjects achieving endoscopic remission at Week 12, defined as a Mayo endoscopic subscore of 0 - Endoscopic remission is defined as endoscopy subscore of 0.
Timepoint [2] 0 0
Week 12
Secondary outcome [3] 0 0
The proportion of subjects achieving endoscopic response at Week 12, defined as a decrease from baseline of at least 1 point in the Mayo endoscopic subscore - Endoscopic response is defined as a 1 point or greater decrease from baseline in the endoscopy subscore.
Timepoint [3] 0 0
Week 12
Secondary outcome [4] 0 0
The proportion of subjects achieving a Rectal Bleeding Score (RBS) = 1 at Week 12 - 0 = No blood seen
= Streaks of blood with stool less than half the time
= Obvious blood with stool most of the time
= Blood alone passed
The daily bleeding score represents the most severe bleeding of the day.
Timepoint [4] 0 0
Week 12
Secondary outcome [5] 0 0
The proportion of subjects achieving clinical remission in the modified Mayo Score (range: 0 to 9, based on stool frequency subscore (SFS), RBS and endoscopy) at Week 12 - Clinical remission in the modified Mayo Score is defined as a score of 2 points or lower, with no individual subscore exceeding 1 point
Timepoint [5] 0 0
Week 12
Secondary outcome [6] 0 0
The proportion of subjects achieving clinical response in the modified Mayo Score at Week 12 - Clinical response in the modified Mayo Score defined as a decrease from baseline at least 2 points and at least 25%, along with a reduction in the RBS of at least 1 point or an absolute RBS of = 1 point
Timepoint [6] 0 0
Week 12
Secondary outcome [7] 0 0
The proportion of subjects achieving clinical remission at Week 8 - Clinical remission at Week 8 is defined as a Partial Mayo Score (PMS) of = 2, with no individual subscore > 1
Timepoint [7] 0 0
Week 8
Secondary outcome [8] 0 0
The proportion of subjects achieving clinical response at Week 8 - Clinical response at Week 8 is defined as a decrease from baseline in the PMS of at least 2 points and at least 25%, along with a reduction in the RBS of at least 1 point or an absolute RBS of = 1 point
Timepoint [8] 0 0
Week 8
Secondary outcome [9] 0 0
Adverse Events (AEs) - An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, aworsening concomitant illness, an injury, or any concomitant impairment of the subject's health, including laboratory test values (as specified by the criteria in Section 11.3), regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a pre-existing condition) should be considered an AE
Timepoint [9] 0 0
Up to 56 weeks

Eligibility
Key inclusion criteria
Subjects must satisfy the following criteria to be enrolled in the study:

- Male or female aged 18 and over at the time of signing the informed consent.

- Must understand and voluntarily sign an informed consent form prior to any study
related assessments/procedures being conducted.

- Must be able to adhere to the study visit schedule and other protocol requirements.

- Diagnosis of Ulcerative Colitis (UC) with a duration of at least 3 months prior to the
Screening Visit..

- Total Mayo Score (TMS) = 6 to = 11 (range: 0-12) at baseline, prior to randomization
in the study.

- Endoscopic subscore = 2 (range: 0-3) on the Mayo score prior to randomization in the
study.

- Subjects are required to have a colonoscopy if not performed within 12 months of the
Screening Visit.

- Subjects must have had a therapeutic failure, been intolerant to, or have a
contraindication to, at least one of the following: oral aminosalicylates (ie,
5-aminosalicylic acid [5-ASA] compounds or sulfasalazine [SSZ]), budesonide, systemic
corticosteroids, or immunosuppressants (eg, 6-mercaptopurine [6-MP], azathioprine
[AZA], or methotrexate [MTX]).

- Subjects receiving oral corticosteroids may continue their use during the study,
provided that the dose (prednisone = 20 mg/day or equivalent, budesonide = 9 mg/day)
has been stable for 3 weeks prior to the Screening Visit. If oral corticosteroids were
recently discontinued, discontinuation must have been completed at least 3 weeks prior
to the Screening Visit. Corticosteroid doses should remain stable until the subject is
eligible to start corticosteroids tapering, beginning at the Week 12 Visit.

- Oral aminosalicylates are permitted during the study, provided that treatment started
at least 6 weeks prior to screening with a stable dose of at least 14 days prior to
the Screening Visit. The dose of oral aminosalicylates must remain stable through the
end of the study.

- Must meet the following laboratory criteria:

- White blood cell count = 3000/mm^3 (= 3.0 X 10^9/L) and <

- 14,000/mm^3 (< 14 X 10^9/L)

- Platelet count = 100,000/mm^3 (= 100 X 10^9/L)

- Serum creatinine = 1.5 mg/dL (= 132.6 µmol/L)

- Aspartate aminotransferase (AST) Serum glutamic-oxaloacetic transaminase (SGOT),
and alanine aminotransferase (ALT), serum glutamic :pyruvic transaminase (SGPT)
ALT (SGPT) - 2 X upper limit of normal (ULN). If initial test shows ALT or AST >
2 times the ULN, one repeat test is allowed during the screening period.

- Total bilirubin = 2 mg/dL (= 34 µmol/L) or albumin > lower limit of normal (LLN).
If initial test result is > 2 g/dL, one repeat test is allowed dirng the
screening period

- Hemoglobin =9 g/dL (=5.6 mmol/L)

- Females of childbearing potential (FCBP) must have a negative pregnancy test
at Screening and the Baseline Visit. While on IP and for at least 28 days
after taking the last dose of IP, FCBP who engage in activity in which
conception is possible must use one of the approved contraceptives.

- Male subjects (including those who have had a vasectomy) who engage in
activity in which conception is possible must use barrier contraception
(male latex condom or nonlatex condom NOT made out of natural [animal]
membrane [for example, polyurethane]) while on investigational product and
for at least 28 days after the last dose of investigational product
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
The presence of any of the following will exclude a subject from enrollment:

- Diagnosis of Crohn's disease, indeterminate colitis, ischemic colitis, microscopic
colitis, radiation colitis or diverticular disease-associated colitis.

- Ulcerative colitis restricted to the distal 15 cm or less (eg, ulcerative proctitis).

- Subjects who have had surgery as a treatment for UC or who, in the opinion of the
Investigator, are likely to require surgery for UC during the study.

- Clinical signs suggestive of fulminant colitis or toxic megacolon.

- Evidence of pathogenic enteric infection.

- History of colorectal cancer or colorectal dysplasia with the exception of adenomatous
colonic polyps that have been completely resected). .

- Prior use of any TNF inhibitor (or any biologic agent).

- Prior use of mycophenolic acid, tacrolimus, sirolimus, cyclosporine or thalidomide.

- Use of IV corticosteroids within 2 weeks of the Screening Visit.

- Use of immunosuppressants (AZA, 6-MP or MTX) within 8 weeks of the Screening Visit.

- Use of topical treatment with 5-ASA or corticosteroid enemas or suppositories within 2
weeks of the Screening Visit.

- History of any clinically significant neurological, renal, hepatic, gastrointestinal,
pulmonary, metabolic, cardiovascular, psychiatric, endocrine, hematological disorder
or disease, or any other medical condition that, in the investigator's opinion, would
preclude participation in the study.

- Prior history of suicide attempt at any time in the subject's lifetime prior to
ramdomization in the study or major psychiatric illness requiring hospitalization
within 3 years of study randomization.

- Any condition, including the presence of laboratory abnormalities, which places the
subject at unacceptable risk if he/she was to participate in the study or confounds
the ability to interpret data from the study.

- Pregnant or breast feeding.

- History of any of the following cardiac conditions within 6 months of screening:
myocardial infarction, acute coronary syndrome, unstable angina, new onset atrial
fibrillation, new onset atrial flutter, second- or third-degree atrioventricular
block, ventricular fibrillation, ventricular tachycardia, heart failure, cardiac
surgery, interventional cardiac catheterization (with or without a stent placement),
interventional electrophysiology procedure, or presence of implanted defibrillator.

- Known active current or history of recurrent bacterial, viral, fungal mycobacterial or
other infections (including but not limited to tuberculosis and atypical mycobacterial
disease and herpes zoster), human immunodeficiency virus (HIV), or any major episode
of infection requiring hospitalization or treatment with intravenous (IV) or oral
antibiotics within 4 weeks of screening.

- Subjects with active hepatitis B infection as described in Appendix E are ineligible
for the study. Subjects without current hepatitis B infection described in Appendix F
may participate in the study.

- Subjects who are confirmed positive for hepatitis C are not eligible for the study.

- History of congenital or acquired immunodeficiency (eg, Common Variable
Immunodeficiency Disease).

- History of malignancy, except for:

- a. Treated (ie, cured) basal cell or squamous

- b. Treated (ie, cured) cervical intraepithelial neoplasia (CIN) or carcinoma in
situ of the cervix with no evidence of recurrence within the previous 5 years

- Any condition that could affect oral drug absorption, including gastric resections,
gastroparesis or bariatric surgery, such as gastric bypass.

- Subjects has received any investigational drug or device within 1 month or 5
elimination half-lives, whichever is longer, prior to the Screening Visit .

- History of alcohol, drug, or chemical abuse within the 6 months prior to screening.

- Known hypersensitivity to apremilast or any excipients in the formulation

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Current
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Concord Repatriation General Hospital - Concord
Recruitment hospital [2] 0 0
Liverpool Hospital - Liverpool
Recruitment hospital [3] 0 0
Mater Adult Hospital - South Brisbane
Recruitment hospital [4] 0 0
Remove - Monash Medical Centre Clayton Campus - Clayton
Recruitment hospital [5] 0 0
Footscray Hospital - Footscray
Recruitment hospital [6] 0 0
Royal Melbourne Hospital - Parkville
Recruitment postcode(s) [1] 0 0
2139 - Concord
Recruitment postcode(s) [2] 0 0
2170 - Liverpool
Recruitment postcode(s) [3] 0 0
4101 - South Brisbane
Recruitment postcode(s) [4] 0 0
3168 - Clayton
Recruitment postcode(s) [5] 0 0
3011 - Footscray
Recruitment postcode(s) [6] 0 0
3050 - Parkville
Recruitment outside Australia
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United States of America
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Alabama
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California
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Connecticut
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Florida
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Illinois
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Iowa
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Kentucky
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Massachusetts
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Michigan
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Mississippi
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New York
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Ohio
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Utah
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Washington
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Plovdiv
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Sofia
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Varna
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Brno
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France
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Clichy
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Nantes
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Nice
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France
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Berlin
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Germany
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Frankfurt
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Germany
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Keil
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Germany
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Mainz
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Germany
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Minden
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Germany
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Szeged
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Bologna
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Italy
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Italy
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Palermo
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Roma
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Groningen
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Auckland
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Christchurch
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Dunedin
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New Zealand
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Hamilton
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Bialystok
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Sopot
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Szczecin
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Torun
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Warsaw
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Warszawa
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Wroclaw
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Russian Federation
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Kazan
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Russian Federation
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Moscow
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Russian Federation
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Rostov on Don
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Russian Federation
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Saratov
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Russian Federation
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St Petersburg
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Ukraine
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Chernivtsi
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Ukraine
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Ivano-Frankivsk
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Ukraine
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Kharkiv
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Ukraine
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Kirovograd
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Ukraine
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Kremenchuk
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Ukraine
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Lviv
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Ukraine
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Odesa
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Ukraine
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Uzhgorod
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Ukraine
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Vinnytsia
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Ukraine
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Zaporizhzhia

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Celgene
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of the study is to evaluate the clinical efficacy, safety and tolerability of
apremilast (30 mg twice daily [BID] and 40 mg BID), compared with placebo, in subjects with
active Ulcerative Colitis (UC).
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Denesh Chitkara, MD
Address 0 0
Celgene Corporation
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries
Contact person responsible for updating information