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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00621894
Recruitment Status : Completed
First Posted : February 22, 2008
Last Update Posted : January 18, 2018
Information provided by (Responsible Party):

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.

Condition or disease Intervention/treatment Phase
Immune Thrombocytopenic Purpura Drug: LGD-4665 Drug: Placebo Phase 2

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 23 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : March 1, 2008
Actual Primary Completion Date : May 1, 2009
Actual Study Completion Date : May 1, 2009

Arm Intervention/treatment
Experimental: LGD4665
LGD-4665: Experimental Thrombopoietin mimetic
Drug: LGD-4665
LGD-4665 Thrombopoietin mimetic
Placebo Comparator: Placebo
Drug: Placebo

Primary Outcome Measures :
  1. Percentage of participants with platelet count >= 50000/µL [ Time Frame: At Week 6 ]
    Response was defined as platelet count >= 50 x1000/uL for participants without Baseline steroid uses; or platelet counts >= 50 x1000/uL and doubling the Baseline platelet counts for participants with baseline steroid uses. Confidence interval of response rate was computed using exact method of binomial proportion.

Secondary Outcome Measures :
  1. Number of participants with time to response by Platelet Counts (platelet counts >= 50,000/µL) [ Time Frame: Week 1, 2, 4 and 6 of part 1 ]
    Response was defined as platelet count >= 50 x1000/uL for participants without baseline steroid uses; or platelet counts >= 50 x1000/uL and doubling the Baseline platelet counts for participants with baseline steroid uses.

  2. Change From Baseline to Last Bleeding Observation During Double-Blind Treatment [ Time Frame: Day 1 (Baseline) and Week 6 ]
    ITP Bleeding Severity Scale was used for the analysis of bleeding score. Bleeding scores were, 0=None, 1=minor, and 2=major. Body sites and bleeding grade analysis was as follows: cutaneous (1= 1-5 bruises; scattered petechiae and 2= > 5 bruises, >2 centimeter [cm]; petechiae), oral mucosa (1= 1 blood blister or > 5 petechiae, gum bleeding < 5 minute[min], 2= multiple blood blisters; gum bleeding > 5 min), epistaxis (1= blood on blowing nose or epistaxis < 5 min, 2= bleeding > 5 min), gastrointestinal (1= occult blood, 2= gross blood), gynecological (1= spotting not at time of period, 2= bleeding not at time of period or very heavy period), urinary (1= microscopic (+ by dipstick), 2= macroscopic), pulmonary(1= possible symptoms but mild, 2= yes), subconjunctival (1= yes, 2= both eyes significantly involved), Intracranial (1= possible symptoms, 2= yes, clinically confirmed). Change from Baseline was calculated as Baseline value minus post-randomization value. Baseline was Day 1value.

  3. Duration of platelet counts >= 50,000/µL of LGD4665 [ Time Frame: Up to Week 6 ]
    Response was defined as platelet count >= 50 x1000/uL for participants without baseline steroid uses; or platelet counts >= 50 x1000/uL and doubling the Baseline platelet counts.A Kaplan-Meier projection of time to response by platelet counts was analyzed.

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00621894

United States, California
University of California San Diego Medical Center
San Diego, California, United States, 92103-8409
University of California, San Francisco
San Francisco, California, United States, 94143-1270
United States, Connecticut
Davis, Posteraro and Wasser, MD's LLP
Manchester, Connecticut, United States, 06040
United States, Florida
Baptist Cancer Institute
Jacksonville, Florida, United States, 32207
Cancer Center of Florida
Orlando, Florida, United States, 32806
United States, Georgia
Georgia Cancer Specialists
Atlanta, Georgia, United States, 30341
United States, Michigan
Karmanos Cancer Center, Wertz Clinical Cancer Center 4HWCRC
Detroit, Michigan, United States, 48201
Henry Ford Health System
Detroit, Michigan, United States, 48202
United States, Missouri
Washington University School of Medicine - St Louis, MO
Saint Louis, Missouri, United States, 63110
United States, New Mexico
New Mexico Oncology Hematology Consultants
Albuquerque, New Mexico, United States, 87109
United States, New York
Joan and Sanford I. Weill Medical College, Cornell University
New York, New York, United States, 10021
Mount Sinai School of Medicine
New York, New York, United States, 10029
United States, Ohio
Case Western Reserve University School of Medicine
Cleveland, Ohio, United States, 44106-7284
Cleveland Clinic Foundation, Univ. of Ohio
Cleveland, Ohio, United States, 44195
United States, Texas
Hematology Oncology Associates of South Texas
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
Study Director: GSK Clinical Trials GlaxoSmithKline

Additional Information:
Responsible Party: GlaxoSmithKline Identifier: NCT00621894     History of Changes
Other Study ID Numbers: L4665-03
First Posted: February 22, 2008    Key Record Dates
Last Update Posted: January 18, 2018
Last Verified: January 2018

Keywords provided by GlaxoSmithKline:
Immune thrombocytopenic purpura
thrombopoietin mimetic

Additional relevant MeSH terms:
Purpura, Thrombocytopenic
Purpura, Thrombocytopenic, Idiopathic
Blood Coagulation Disorders
Hematologic Diseases
Pathologic Processes
Skin Manifestations
Signs and Symptoms
Thrombotic Microangiopathies
Blood Platelet Disorders
Immune System Diseases
Hemorrhagic Disorders
Autoimmune Diseases