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

Sponsored by:	Ligand Pharmaceuticals
Information provided by:	Ligand Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT00621894

Purpose

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	Intervention	Phase
Immune Thrombocytopenic Purpura	Drug: LGD-4665 Drug: Placebo	Phase II

Genetics Home Reference related topics: hemophilia thrombotic thrombocytopenic purpura

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study
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

Further study details as provided by Ligand Pharmaceuticals:

Primary Outcome Measures:

Platelet counts [ Time Frame: Week 6 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Bleeding score [ Time Frame: Weeks 1 - 20 ] [ Designated as safety issue: No ]

Estimated Enrollment:	24
Study Start Date:	March 2008
Estimated Study Completion Date:	May 2009
Estimated Primary Completion Date:	December 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental LGD-4665: Experimental Thrombopoietin mimetic	Drug: LGD-4665 LGD-4665 Thrombopoietin mimetic
2: Placebo Comparator	Drug: Placebo Placebo

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

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00621894

Locations

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
St. Louis, Missouri, United States, 63110
United States, New Mexico
New Mexico Oncology Hematology Consultants
Albuquerque, New Mexico, United States, 87109
United States, New York
Mount Sinai School of Medicine
New York, New York, United States, 10029
Joan and Sanford I. Weill Medical College, Cornell University
New York, New York, United States, 10021
United States, Ohio
Cleveland Clinic Foundation, Univ. of Ohio
Cleveland, Ohio, United States, 44195
Case Western Reserve University School of Medicine
Cleveland, Ohio, United States, 44106-7284
United States, Texas
Hematology Oncology Associates of South Texas
San Antonio, Texas, United States, 78229

Sponsors and Collaborators

Ligand Pharmaceuticals

Investigators

Principal Investigator:

James Bussel, M.D.

Joan and Sanford I. Weill Medical College, Cornell University

More Information

No publications provided

Responsible Party:	Ligand Pharmaceuticals ( Victor Stevens, Ph.D, Director of Clinical Research )
Study ID Numbers:	L4665-03
Study First Received:	February 12, 2008
Last Updated:	January 9, 2009
ClinicalTrials.gov Identifier:	NCT00621894 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by Ligand Pharmaceuticals:

ITP
Immune thrombocytopenic purpura
thrombopoietin mimetic

oral
Ph II
Patients diagnosed with ITP who have had one or more prior treatments and are thrombocytopenic with platelet counts < 30,000/µL

Study placed in the following topic categories:

Purpura
Thrombocytopathy
Signs and Symptoms
Thrombocytopenia
Hematologic Diseases

Blood Platelet Disorders
Blood Coagulation Disorders
Hemostatic Disorders
Purpura, Thrombocytopenic

Additional relevant MeSH terms:

Purpura
Signs and Symptoms
Skin Manifestations
Thrombocytopenia
Immune System Diseases

Hematologic Diseases
Blood Platelet Disorders
Blood Coagulation Disorders
Purpura, Thrombocytopenic

ClinicalTrials.gov processed this record on May 06, 2009