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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
23
University of California San Diego Medical Center
San Diego, California, United States
University of California, San Francisco
San Francisco, California, United States
Davis, Posteraro and Wasser, MD's LLP
Manchester, Connecticut, United States
Baptist Cancer Institute
Jacksonville, Florida, United States
Cancer Center of Florida
Orlando, Florida, United States
Georgia Cancer Specialists
Atlanta, Georgia, United States
Karmanos Cancer Center, Wertz Clinical Cancer Center 4HWCRC
Detroit, Michigan, United States
Henry Ford Health System
Detroit, Michigan, United States
Washington University School of Medicine - St Louis, MO
St Louis, Missouri, United States
New Mexico Oncology Hematology Consultants
Albuquerque, New Mexico, United States
...and 5 more locations
Percentage of participants with platelet count >= 50000/µL
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.
Time frame: At Week 6
Number of participants with time to response by Platelet Counts (platelet counts >= 50,000/µL)
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.
Time frame: Week 1, 2, 4 and 6 of part 1
Change From Baseline to Last Bleeding Observation During Double-Blind Treatment
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.
Time frame: Day 1 (Baseline) and Week 6
Duration of platelet counts >= 50,000/µL of LGD4665
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.
Time frame: Up to Week 6
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