Efficacy and Safety Study of CC-292 Versus Placebo as Co-therapy With Methotrexate in Active Rheumatoid Arthritis

This is a Phase 2a, multicenter, randomized, double-blind, placebo-controlled,
proof-of-concept study to determine the efficacy and safety of CC-292 (375 mg PO daily) on a
stable background of MTX therapy in female subjects with active RA.

Approximately 80 female subjects with active RA will be randomized 1:1 into two dose groups:
active CC-292 (375 mg PO daily) or identically-appearing placebo capsules for 4 weeks

Inclusion Criteria:

- Female between 18 and 80 years of age (inclusive) at the time of signing the informed
consent.

- Must meet the 2010 ACR/EULAR Classification Criteria for RA (Appendix A), have RA for
at least 6 months and must continue to have active RA at the time of randomization
despite at least 3 months of treatment with stable doses of MTX (7.5 to 25 mg/week
oral or parenteral) for at least 4 weeks prior to randomization.

- Must have been treated with MTX for at least 3 months prior to randomization, and
must be on a stable dose between 7.5 and 25 mg/week (PO or parenteral, not both) for
at least 4 weeks prior to randomization. Subjects will be required to maintain their
stable dose through Day 28/Week 4 of the study. Oral folate supplementation is
required with a minimum dose of 5 mg/week (ie, folic acid) while the subject is
taking MTX. Leucovorin may be used instead of folic acid and may be dosed up to 10
mg/week orally.

- Sulfasalazine is allowed as a concomitant medication, however, subject must be on a
stable dose for at least 4 weeks prior to randomization and through Day 28/Week 4 of
the study.

- Hydroxychloroquine or chloroquine is allowed as concomitant medications, however,
subject must be on a stable dose for at least 4 weeks prior to randomization and
through Day 28/Week 4 of the study.

- Modification of Diet in Renal Disease formula (MDRD) estimated glomerular filtration
rate (MDRD eGFR) ≥ 60 mL/min/1.73m2+

Exclusion Criteria:

- Male subjects

- Any condition that could affect CC-292 absorption, including gastric restrictions,
bariatric surgery, such as gastric bypass, and clinical conditions that are
associated with decreased intragastric acid production such as acid pernicious
anemia.

- Currently using treatment with DMARDs (other than sulfasalazine, hydroxychloroquine
or chloroquine and MTX), including biologics. Previous use is only allowed after
adequate washout (4 weeks or 5 half-lives, whichever is longer) prior to
randomization.

- Previous treatment with any cell depleting therapies, including investigational
agents (eg, CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19 and anti-CD20) within 6
months of screening.

- Treatment with intravenous gamma globulin, plasmapheresis or Prosorba® column within
2 weeks prior to randomization.

- Intra-articular or parenteral corticosteroids are not allowed within 2 weeks prior to
randomization.