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

A Phase IIA Randomized, Double-Blind, Placebo-Controlled Study of LGD-4665 in Patients With Immune Thrombocytopenic Purpura (ITP) With an Open Label Extension

The purpose of this study is to assess the ability of LGD-4665 given daily by mouth to increase platelet counts in the treatment of patients with ITP (immune thrombocytopenic purpura). LGD-4665 increased platelet counts safely and tolerably compared to placebo in healthy volunteers. This study will examine the safety, tolerability and efficacy of 7.5 mg capsules of LGD-4665 to increase platelets compared to placebo, randomized 2:1, during blinded treatment for 6 weeks. Evaluation of platelet counts, bleeding scores and safety parameters will be done weekly. All patients are eligible to continue on active, open LGD-4665 treatment for an additional 12 weeks with optimal adjustment of dose for each patient.

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