Effect of UV Exposure on the PD of Multiple Doses of CC-90001 and Pilot Food Effect Study

Part 1 is an open-label, multiple-dose, 3-period, fixed-sequence study, to evaluate the
effect of CC-90001 on JNK activity following UV irradiation. On the first day prior to
dosing (baseline), and on the 6th day of each dosing period (Days 6, 12, and 18), twice the
MED intensity of UV light will be administered to delineated sites on the subjects'
buttocks. The irradiation at baseline (Day -1) should be administered at approximately the
same time that irradiation is scheduled on Days 6, 12, and 18, which is at 2 hours post
dose. Eight hours after UV irradiation, a skin punch biopsy will be taken from the UV
exposure site. The end of confinement will be Day 19. The follow-up visit will occur 7-10
days (ie, Day 25 to Day 28) following the last dose in Period 3. An early termination (ET)
visit will occur within 10 days of the day of discontinuation. The MED will be determined
within 10 days of dosing in Period 1. All subjects will receive the following doses of
CC-90001 in the fixed sequence below: Treatment A: 60 mg CC-90001 as AIC, QD x 6 days;
Treatment B: 160 mg CC-90001 as AIC, QD x 6 days; and Treatment C: 400 mg of CC-90001 as
AIC, QD x 6 days. Subjects will be confined at the unit from Day -1 until discharge on Day
19 after all safety assessments.

In Part 2 subjects will be assigned randomly to one of three dosing sequences during which
they will receive one of the following dosing regimens:

- Treatment D: 2 x 100 mg CC-90001 as AIC, single oral dose administered under fasted
conditions.

- Treatment E: 1 x 200 mg CC-90001 [formulated tablet(s)] single oral dose administered
under fasted conditions

- Treatment F: 1 x 200 mg CC-90001 [formulated tablet(s)] single oral dose administered
under fed conditions (standard high fat breakfast).

Inclusion Criteria:

1. Must understand and voluntarily sign a written Informed Consent Document (ICD) prior
to any study-related assessments/procedures being performed

2. Must be able to communicate with the Investigator and to understand and adhere to the
study visit schedule and other protocol requirements

3. Must be a male or female*, aged 18 years of age to 65 years of age (inclusive) at the
time of signing the ICD

* Women of child-bearing potential (WCBP)*must agree to ongoing pregnancy testing
during the course of the study, and at the end of the study. This applies even if the
subject practices true abstinence from heterosexual contact

1. The female subjects must either commit to true abstinence** from heterosexual
contact (which must be reviewed on a monthly basis) or agree to use, and be able
to comply with, 2 highly effective contraception without interruption, 28 days
prior to starting study drug, during the study therapy (including dose
interruptions), and for at least 28 days after discontinuation of study drug

2. Females not of child-bearing potential should have been either surgically
sterilized at least 6 months prior to screening (hysterectomy or bilateral tubal
ligation) or be postmenopausal (defined as 24 months with no menses prior to
Screening, AND with a plasma follicle stimulating hormone (FSH) > 40 IU/L at
screening). Documentation will be required in cases of tubal ligation

4. Males must practice true abstinence** or agree to use a condom (a latex condom is
recommended) during sexual contact with a pregnant female or a WCBP while on study
drug, or while participating in this study, during dose interruptions and for at
least 28 days following study drug discontinuation, even if he has undergone a
successful vasectomy

** True abstinence is acceptable when this is in line with the preferred and usual
lifestyle of the subject [Periodic abstinence (eg, calendar, ovulation,
symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of
contraception]

5. Has a body mass index (BMI = weight [kg]/(height [m2]) between 18 and 33 kg/m2
(inclusive)

6. Must be healthy as determined by the Investigator on the basis of medical history,
physical examination, clinical laboratory test results, vital signs, and 12-lead ECGs

- Must be afebrile (febrile is defined as ≥ 38 °C or 100.3° Fahrenheit)

- Systolic blood pressure must be in the range of 80 to 140 mmHg, diastolic blood
pressure must be in the range of 40 to 90 mmHg, and pulse rate must be in the
range of 40 to 110 bpm

- QTcF value ≤ 430 msec for male subjects and ≤ 450 msec for female subjects. An
ECG may be repeated up to 3 times to determine subject eligibility

7. Additional criteria for Part 1 only:

1. Must be Fitzpatrick skin type I or II

2. Must have a valid MED obtained within 10 days prior to dosing

Exclusion Criteria:

1. History (ie, within 3 years) of any clinically significant neurological,
gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, endocrine,
hematological, dermatological, psychological, or other major disorders

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

3. Use of any prescribed systemic or topical medication, including vaccines, within 30
days of the first dose

4. Use of any non-prescribed systemic or topical medication (including herbal medicines)
within 14 days of the first dose administration (with the exception of
vitamin/mineral supplements)

5. Use of any metabolic enzyme inhibitors or inducers (ie, CYP3A inducers and inhibitors
or St. John's wort) within 30 days of the first dose administration

a. The University of Indiana "Cytochrome P450 Drug Interaction Table" should be used
to determine inhibitors and/or inducers of CYP 3A4
(http://medicine.iupui.edu/clinpharm/ddis/table/aspx)

6. Presence of any surgical or medical conditions possibly affecting drug absorption,
distribution, metabolism and excretion (ADME), eg, bariatric procedure

a. Appendectomy and cholecystectomy are acceptable

7. Donated blood or plasma within 8 weeks before the first dose administration

8. History of drug abuse (as defined by the current version of the Diagnostic and
Statistical Manual [DSM]) within 2 years before dosing, or positive drug screening
test reflecting consumption of illicit drugs)

9. History of alcohol abuse (as defined by the current version of the DSM) within 2
years before dosing, or positive alcohol screen

10. Known to have serum hepatitis or known to be a carrier of the hepatitis B surface
antigen (HBsAg), or hepatitis C antibody (HCVAb), or have a positive result to the
test for HIV antibodies at Screening

11. Exposed to an investigational drug (new chemical entity) within 30 days preceding the
first dose administration, or 5 half-lives of that investigational drug, if known
(whichever is longer)

12. Smoke more than 10 cigarettes per day, or the equivalent in other tobacco products
(self reported)

13. Subject has a history of multiple drug allergies (ie, 2 or more)

Additional Exclusion Criteria for Subjects in Part 1 Only:

1. Inability to evaluate the skin in and around the test sites due to sunburn, tans,
uneven skin tones, tattoos, scars, excessive hair, numerous freckles, or any other
disfiguration

2. Used any creams or lotions (ie, containing sun protection factor [SPF]) in the test
area (ie, buttocks) within 7 days of study start (Day 1)

3. Participation in any test for irritation or sensitization or any test involving UV
exposures on the test area within four weeks of study start

4. Participation in another study requiring biopsy (on the planned test area) within the
past 2 months

5. History of wound healing or blood-clotting abnormality

6. History of keloid formation or hypertrophic scarring following skin injury

7. History of severe reactions from exposure to sunlight

8. History of allergy to lidocaine or other similar local anesthetics

9. History of allergy to epinephrine