- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00621894
Oral LGD-4665 Versus Placebo in Adults With Immune Thrombocytopenic Purpura (ITP) for 6 Weeks Plus Open Treatment Continuation
January 16, 2018 updated by: GlaxoSmithKline
A Phase IIA Randomized, Double-Blind, Placebo-Controlled Study of LGD-4665 in Patients With Immune Thrombocytopenic Purpura (ITP) With an Open Label Extension
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
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
Enrollment (Actual)
23
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
California
-
San Diego, California, United States, 92103-8409
- University of California San Diego Medical Center
-
San Francisco, California, United States, 94143-1270
- University of California, San Francisco
-
-
Connecticut
-
Manchester, Connecticut, United States, 06040
- Davis, Posteraro and Wasser, MD's LLP
-
-
Florida
-
Jacksonville, Florida, United States, 32207
- Baptist Cancer Institute
-
Orlando, Florida, United States, 32806
- Cancer Center of Florida
-
-
Georgia
-
Atlanta, Georgia, United States, 30341
- Georgia Cancer Specialists
-
-
Michigan
-
Detroit, Michigan, United States, 48202
- Henry Ford Health System
-
Detroit, Michigan, United States, 48201
- Karmanos Cancer Center, Wertz Clinical Cancer Center 4HWCRC
-
-
Missouri
-
Saint Louis, Missouri, United States, 63110
- Washington University School of Medicine - St Louis, MO
-
-
New Mexico
-
Albuquerque, New Mexico, United States, 87109
- New Mexico Oncology Hematology Consultants
-
-
New York
-
New York, New York, United States, 10029
- Mount Sinai School of Medicine
-
New York, New York, United States, 10021
- Joan and Sanford I. Weill Medical College, Cornell University
-
-
Ohio
-
Cleveland, Ohio, United States, 44106-7284
- Case Western Reserve University School of Medicine
-
Cleveland, Ohio, United States, 44195
- Cleveland Clinic Foundation, Univ. of Ohio
-
-
Texas
-
San Antonio, Texas, United States, 78229
- Hematology Oncology Associates of South Texas
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: Placebo
|
Placebo
|
Experimental: LGD4665
LGD-4665: Experimental Thrombopoietin mimetic
|
LGD-4665 Thrombopoietin mimetic
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
At Week 6
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Week 1, 2, 4 and 6 of part 1
|
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.
|
Day 1 (Baseline) and Week 6
|
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.
|
Up to Week 6
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
March 1, 2008
Primary Completion (Actual)
May 1, 2009
Study Completion (Actual)
May 1, 2009
Study Registration Dates
First Submitted
February 12, 2008
First Submitted That Met QC Criteria
February 21, 2008
First Posted (Estimate)
February 22, 2008
Study Record Updates
Last Update Posted (Actual)
January 18, 2018
Last Update Submitted That Met QC Criteria
January 16, 2018
Last Verified
January 1, 2018
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Immune System Diseases
- Autoimmune Diseases
- Hematologic Diseases
- Hemorrhage
- Hemorrhagic Disorders
- Blood Coagulation Disorders
- Skin Manifestations
- Thrombocytopenia
- Blood Platelet Disorders
- Thrombotic Microangiopathies
- Purpura
- Purpura, Thrombocytopenic
- Purpura, Thrombocytopenic, Idiopathic
Other Study ID Numbers
- L4665-03
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Immune Thrombocytopenic Purpura
-
Harbour BioMed (Guangzhou) Co. Ltd.RecruitingPrimary Immune Thrombocytopenic PurpuraChina
-
Novartis PharmaceuticalsCompletedImmune Thrombocytopenic Purpura (ITP)Spain, Italy, Greece, Switzerland, United Kingdom, France, Turkey, Russian Federation, Brazil, Austria, Mexico, Oman, Chile, Japan, United States
-
Institute of Hematology & Blood Diseases HospitalRecruitingPrimary Immune Thrombocytopenic PurpuraChina
-
Momenta Pharmaceuticals, Inc.TerminatedImmune Thrombocytopenic Purpura (ITP)United States, Poland, Hungary, Netherlands, Italy, Spain, Belgium
-
National Institute of Blood and Marrow Transplant...NovartisUnknownImmune Thrombocytopenic Purpura (ITP)Pakistan
-
Instituto Grifols, S.A.CompletedImmune (Idiopathic) Thrombocytopenic PurpuraSpain, Russian Federation, United Kingdom
-
AmgenCompletedThrombocytopenia | Immune Thrombocytopenia | Idiopathic Thrombocytopenic Purpura | Thrombocytopenia in Pediatric Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP) | Thrombocytopenia in Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP) | Thrombocytopenic PurpuraUnited States, Canada, Australia
-
Neufeld, Ellis J, MD, PhDGenentech, Inc.; Biogen; Glaser Pediatric Research Network; Terrana ITP Research...CompletedImmune Thrombocytopenic Purpura (ITP) | Idiopathic Thrombocytopenic Purpura (ITP)United States
-
David Gomez AlmaguerUnknownThrombotic Thrombocytopenic Purpura | Immune ThrombocytopeniaMexico
-
Anthera PharmaceuticalsWithdrawnIdiopathic Thrombocytopenic Purpura | Immune Thrombocytopenic Purpura
Clinical Trials on Placebo
-
SamA Pharmaceutical Co., LtdUnknownAcute Bronchitis | Acute Upper Respiratory Tract InfectionKorea, Republic of
-
National Institute on Drug Abuse (NIDA)CompletedCannabis UseUnited States
-
AstraZenecaParexel; Spandauer Damm 130; 14050; Berlin, GermanyCompletedMale Subjects With Type II Diabetes (T2DM)Germany
-
Heptares Therapeutics LimitedCompletedPharmacokinetics | Safety IssuesUnited Kingdom
-
GlaxoSmithKlineCompletedPulmonary Disease, Chronic ObstructiveUnited Kingdom, Netherlands
-
Shijiazhuang Yiling Pharmaceutical Co. LtdXuanwu Hospital, BeijingCompleted
-
GlaxoSmithKlineCompletedInfections, BacterialUnited States
-
ItalfarmacoCompletedBecker Muscular DystrophyNetherlands, Italy
-
West Penn Allegheny Health SystemCompletedAsthma | Allergic RhinitisUnited States