TRF-1101 Assessment in Sickle Cell Disease

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

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.

Study Overview

• Status: Terminated
• Conditions: Sickle Cell Disease
• Intervention / Treatment: Drug: TRF-1101; Drug: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20060
      • Howard University
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Medical College of Georgia
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University of Illinios Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Wayne State University Medical Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina

Participation Criteria

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:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: TRF-1101; Daily treatment with TRF-1101	Drug: TRF-1101; once daily treatment with 300 mg orally for 12 weeks
PLACEBO_COMPARATOR: Placebo; Daily treatment with placebo	Drug: Placebo; Daily treatment with TRF-1101 vehicle for 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
endothelial cell injury/inflammation	Throughout trial

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: TRF Pharma, Inc
• Investigators: Study Director: Stephen H Embury, M.D., TRF Pharma, Inc

Study record dates

Study Major Dates

• Study Start: July 1, 2008
• Primary Completion (ACTUAL): May 1, 2009
• Study Completion (ACTUAL): May 1, 2009

Study Registration Dates

• First Submitted: October 14, 2008
• First Submitted That Met QC Criteria: October 14, 2008
• First Posted (ESTIMATE): October 16, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): May 11, 2009
• Last Update Submitted That Met QC Criteria: May 7, 2009
• Last Verified: May 1, 2009

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Anemia, Sickle Cell
• Other Study ID Numbers: 1101-201