TRF-1101 Assessment in Sickle Cell Disease

Study Overview
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Brief Summary
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This study is designed to assess the safety, tolerability, and activity of TRF-1101 on microvascular blood flow, vascular endothelial injury, and vasoocclusive pain associated with sickle cell disease.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety and Activity of TRF-1101 on Microvascular Blood Flow, Vascular Endothelial Injury, and Vasoocclusive Pain in Patients With Sickle Cell Disease

Conditions
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Sickle Cell Disease

Intervention / Treatment
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* Drug: TRF-1101
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be 18 years of age or older at the time of informed consent; Have a diagnosis of homozygous sickle cell anemia or sickle cell-beta° thalassemia; Have had 2 - 10 documented pain crises in the past year (pain crises are defined as visits to a medical clinic, Emergency Department or hospital, being bedridden and requiring constant analgesia at home for at least three days, or having a three-day interruption of life's activities [i.e., school, work, planned leisure activity] because of pain); If female and of child bearing potential, have a negative serum or urine pregnancy test and be using an effective birth-control method with a history of reliability for the individual patient (use of mifepristone is not allowed); Be properly informed of the nature and risks of the clinical investigation, be willing and able to comply with all clinical investigation-related procedures and assessments, and sign an Institutional Review Board (IRB) approved Informed Consent Form prior to entering the clinical investigation. Exclusion Criteria: Have a history of abnormal bleeding, stroke, moya moya vascular malformations, or any other contraindication to anticoagulation; Be currently taking anticoagulant or thrombolytic medication; Be currently taking an endothelin receptor antagonist, e.g., bosentan (Tracleer®); Have a known sensitivity or allergy to heparin or related drugs; Have a history of thrombocytopenia (platelet count < 100 x 103/mm3) induced by heparin or related drugs; Have had fewer than 2 documented pain crises in the past year; Have had a pain crisis within one month of screening or randomization; If currently on or recently discontinued hydroxyurea treatment, have initiated or discontinued treatment or changed regimen within the past 6 months; Have had a transfusion within last 120 days or have HbA% > 15% from prior transfusion; Creatinine levels > 1.53 mg/dL (135 umol/L); ALT levels ≥ 3 times normal; Platelet count < 100 x 103/mm3; INR > 2.0; Be unable to tolerate oral medications; Have unreliable venous access; Be noncompliant with regular care; Have a positive pregnancy test, be currently lactating, or be trying to become pregnant; Have participation in an investigational drug or medical device study within previous 30 days; Have any other condition or circumstance that in the opinion of the Investigator makes the patient a poor candidate for participation in the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TRF-1101<br>Daily treatment with TRF-1101 | Drug: TRF-1101<br>* once daily treatment with 300 mg orally for 12 weeks<br>|
| Placebo Comparator: Placebo<br>Daily treatment with placebo | Drug: Placebo<br>* Daily treatment with TRF-1101 vehicle for 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| endothelial cell injury/inflammation |  | Throughout trial | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Microvascular blood flow and trends in frequency of vasoocclusive pain |  | throughout trial |