Oral LGD-4665 Versus Placebo in Adults With Immune Thrombocytopenic Purpura (ITP) for 6 Weeks Plus Open Treatment Continuation

This is a Phase IIA study with two parts to the design.

- Part 1 is a randomized, double-blinded, placebo-controlled treatment of 7.5 mg/day
LGD-4665 versus placebo in approximately 24 patients with ITP who have been treated with
at least one prior therapy for ITP. Patients will be randomized in a ratio of 1:2
(placebo: 7.5 mg/day LGD-4665) for 6 weeks of treatment. Platelet counts, bleeding
scores, vital signs, physical exams and laboratory tests will be assessed weekly.
Treatment groups will be analyzed for efficacy by the percentage of patients with
platelet counts two times baseline and ≥ 50,000/uL at 6 weeks of treatment, and for
safety by adverse events, vital signs, physical exams, laboratory tests and use of ITP
rescue medications or transfusions.

- Part 2 is an extension of study treatment with open label LGD-4665. All patients who
participate in the Part 1 randomized double-blind treatment of this Ph IIA trial are
eligible to continue open label treatment with LGD-4665 for up to 3 months at an
appropriate dose for the safe maintenance of platelet counts (≥ 50,000/uL to ≤
200,000/uL). Assessments of effectiveness and safety will be made at 2 and 4 week
intervals.

Inclusion Criteria:

- Adults 18 years or older

- Diagnosis of ITP for at least 3 months consistent with ASH guidelines

- Treated with one or more prior therapies for ITP and platelet counts < 30,000/µL or <
50,000/µL if on a stable oral corticosteroid for ≥ 4 weeks, supported by 2 platelet
counts in prior 30 days

- Laboratory results within normal range except for the following analytes

- Hemoglobin ≥ 10 g/dL

- Absolute neutrophil counts > 1000/mL

- ALT ≤ 1.5X ULN

- AST ≤ 1.5X ULN

- Creatinine < 1.5X ULN

- Bilirubin < 1.5X ULN

- BUN < 1.5X ULN

- PT < 1.5X ULN

- aPTT <1.5X ULN

- Women of child-bearing potential must have a negative serum pregnancy test within 4
days prior to the first dose of study treatment and agree to practice an approved
method of contraception or abstinence from sexual intercourse.

- Willing to sign a written informed consent

Exclusion criteria:

- History of heart attack or cardiovascular disease

- Known history of arterial or venous thrombosis

- More than 3 risk factors for thromboembolic events (diabetes, smoker, using oral
contraception, using estrogen therapy, hypertriglyceridemia, average cholesterol > 240
mg/dL, treatment for hypertension)

- Active cancer or a history of bone marrow disorders

- Women who are pregnant or nursing

- History of alcohol/drug abuse or dependence within one year

- Listed medications dosed within:

- 4 weeks of the first dose of the study treatment:

- Use of Rituximab

- Use of cytotoxic agents

- Use of Cyclosporine and other immunomodulators

- Use of an investigational drug

- 2 weeks of the first dose of the study treatment:

- Use of Danazol

- Use of Azathioprine

- Use of Mycophenolate mofetil and pulsed-dose steroids

- 1 week of the first dose of the study treatment:

- Use of Anti-D (WinRho®)

- Use of IVIG

- Had a platelet transfusion

- Use of herbal/dietary supplements (excluding vitamins and mineral
supplements)

- 3 days of the first dose of the study treatment

- Use of aspirin, aspirin containing compounds

- salicylates

- milk of magnesia

- non-steroidal anti-inflammatory drugs (unless prescribed for heart disease)

- History of platelet aggregation that would prevent measurement of platelet counts

- Known active infection with HIV, hepatitis B, or hepatitis C

- In the Investigator's opinion, the patient is not able to comply with requirements of
the study