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

Primary Purpose

Immune Thrombocytopenic Purpura

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
LGD-4665
Placebo
Sponsored by
GlaxoSmithKline
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Immune Thrombocytopenic Purpura focused on measuring Immune thrombocytopenic purpura, thrombopoietin mimetic, ITP

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of California San Diego Medical Center
  • University of California, San Francisco
  • Davis, Posteraro and Wasser, MD's LLP
  • Baptist Cancer Institute
  • Cancer Center of Florida
  • Georgia Cancer Specialists
  • Karmanos Cancer Center, Wertz Clinical Cancer Center 4HWCRC
  • Henry Ford Health System
  • Washington University School of Medicine - St Louis, MO
  • New Mexico Oncology Hematology Consultants
  • Joan and Sanford I. Weill Medical College, Cornell University
  • Mount Sinai School of Medicine
  • Case Western Reserve University School of Medicine
  • Cleveland Clinic Foundation, Univ. of Ohio
  • Hematology Oncology Associates of South Texas

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

LGD4665

Placebo

Arm Description

LGD-4665: Experimental Thrombopoietin mimetic

Placebo

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.

Full Information

First Posted
February 12, 2008
Last Updated
January 16, 2018
Sponsor
GlaxoSmithKline
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1. Study Identification

Unique Protocol Identification Number
NCT00621894
Brief Title
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

2. Study Status

Record Verification Date
January 2018
Overall Recruitment Status
Completed
Study Start Date
March 1, 2008 (Actual)
Primary Completion Date
May 1, 2009 (Actual)
Study Completion Date
May 1, 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Immune Thrombocytopenic Purpura
Keywords
Immune thrombocytopenic purpura, thrombopoietin mimetic, ITP

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
23 (Actual)

8. Arms, Groups, and Interventions

Arm Title
LGD4665
Arm Type
Experimental
Arm Description
LGD-4665: Experimental Thrombopoietin mimetic
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo
Intervention Type
Drug
Intervention Name(s)
LGD-4665
Intervention Description
LGD-4665 Thrombopoietin mimetic
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
Percentage of participants with platelet count >= 50000/µL
Description
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
Secondary Outcome Measure Information:
Title
Number of participants with time to response by Platelet Counts (platelet counts >= 50,000/µL)
Description
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
Title
Change From Baseline to Last Bleeding Observation During Double-Blind Treatment
Description
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
Title
Duration of platelet counts >= 50,000/µL of LGD4665
Description
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
University of California San Diego Medical Center
City
San Diego
State/Province
California
ZIP/Postal Code
92103-8409
Country
United States
Facility Name
University of California, San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94143-1270
Country
United States
Facility Name
Davis, Posteraro and Wasser, MD's LLP
City
Manchester
State/Province
Connecticut
ZIP/Postal Code
06040
Country
United States
Facility Name
Baptist Cancer Institute
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32207
Country
United States
Facility Name
Cancer Center of Florida
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States
Facility Name
Georgia Cancer Specialists
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30341
Country
United States
Facility Name
Karmanos Cancer Center, Wertz Clinical Cancer Center 4HWCRC
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Henry Ford Health System
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
Washington University School of Medicine - St Louis, MO
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
New Mexico Oncology Hematology Consultants
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87109
Country
United States
Facility Name
Joan and Sanford I. Weill Medical College, Cornell University
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Mount Sinai School of Medicine
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Case Western Reserve University School of Medicine
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106-7284
Country
United States
Facility Name
Cleveland Clinic Foundation, Univ. of Ohio
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Hematology Oncology Associates of South Texas
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States

12. IPD Sharing Statement

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

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