Clinical trial NCT00621894: Oral LGD-4665 Versus Placebo in Adults With Immune Thrombocytopenic Purpura (ITP) for 6 Weeks Plus Open Treatment Continuation
Official title: A Phase IIA Randomized, Double-Blind, Placebo-Controlled Study of LGD-4665 in Patients With Immune Thrombocytopenic Purpura (ITP) With an Open Label Extension
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Immune Thrombocytopenic Purpura
Keywords: Immune thrombocytopenic purpura
thrombopoietin mimetic
ITP
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2008-02-22
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Percentage of participants with platelet count >= 50000/µL
timeFrame: At Week 6
Secondary outcomes:
measure: Number of participants with time to response by Platelet Counts (platelet counts >= 50,000/µL)
timeFrame: Week 1, 2, 4 and 6 of part 1
measure: Change From Baseline to Last Bleeding Observation During Double-Blind Treatment
timeFrame: Day 1 (Baseline) and Week 6
measure: Duration of platelet counts >= 50,000/µL of LGD4665
timeFrame: Up to Week 6
Other outcomes:
Locations:
city: San Diego
country: United States
facility: University of California San Diego Medical Center
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Manchester
country: United States
facility: Davis, Posteraro and Wasser, MD's LLP
state: Connecticut
city: Jacksonville
country: United States
facility: Baptist Cancer Institute
state: Florida
city: Orlando
country: United States
facility: Cancer Center of Florida
state: Florida
city: Atlanta
country: United States
facility: Georgia Cancer Specialists
state: Georgia
city: Detroit
country: United States
facility: Karmanos Cancer Center, Wertz Clinical Cancer Center 4HWCRC
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine - St Louis, MO
state: Missouri
city: Albuquerque
country: United States
facility: New Mexico Oncology Hematology Consultants
state: New Mexico
city: New York
country: United States
facility: Joan and Sanford I. Weill Medical College, Cornell University
state: New York
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: Cleveland
country: United States
facility: Case Western Reserve University School of Medicine
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation, Univ. of Ohio
state: Ohio
city: San Antonio
country: United States
facility: Hematology Oncology Associates of South Texas
state: Texas
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: