Anemia sickel cell disease
Conditions
Interventions
Participants receiving 1500 mg GBT440 will receive five 300 mg capsules or
tablets, administered orally, once daily
participants receiving 900 mg GBT440
will receive three 300 mg capsules or tablets, and 2 placebo capsules or
tablets administered orally, once daily. Participants randomized to placebo
will receiv
Anemia
Sickle Cell Disease
Sponsors
Global Blood Therapeutics, Inc.
Eligibility
Age
12 Years to 64 Years
Inclusion criteria
Inclusion criteria: 1. Male or female study participants with Sickle Cell Disease: * Documentation of SCD genotype (HbSS, HbSC, HbS* thalassemia or other sickle cell syndrome variants) may be based on history of laboratory testing or must be confirmed by laboratory testing during screening 2. Participants have had at least 1 episode of VOC in the past 12 months. For study eligibility, VOC is defined as a previously documented episode of ACS or acute painful crisis (for which there was no explanation other than VOC) which required prescription or healthcare professionalinstructed use of analgesics for moderate to severe pain (documentation must exist in the patient medical record prior to Screening) 3. Age 12 to 65 years 4. Hemoglobin (Hb) *6.0 and *10.5 g/dL during screening 5. Absolute reticulocyte count and % reticulocyte count must be >1.5 × ULN during Screening 6. For participants taking hydroxyurea (HU), the dose of HU (mg/kg) must be stable for at least 3 months prior to signing the ICF and with no anticipated need for dose adjustments during the study, in the opinion of the Investigator 7. Participants must demonstrate 75% compliance with ePRO measure completion to be enrolled (participants will be given an ePRO device for at least 28 days during Screening; participants who are 60 to 74% compliant can re-screen once with Investigator approval; re-screening is not allowed for participants who are
Exclusion criteria
Exclusion criteria: 1. More than 10 VOCs within the past 12 months that required a hospital, emergency room or clinic visit 2. Female who is breast feeding or pregnant 3. Patients who are receiving regularly scheduled blood (RBC) transfusion therapy (also termed chronic, prophylactic, or preventive transfusion) or have received a RBC transfusion for any reason within 28 days of signing the ICF 4. Hospitalized for sickle cell crisis or other vaso-occlusive event within 14 days of signing the ICF (i.e., a vaso-occlusive event cannot be within 14 days prior to ICF) 5. Hepatic dysfunction characterized by alanine aminotransferase (ALT) >4 × ULN 6. Participants with clinically significant bacterial, fungal, parasitic or viral infection which require therapy: * Participants with acute bacterial infection requiring antibiotic use should delay screening/enrollment until the course of antibiotic therapy has been completed. * Participants with known active hepatitis A, B, or C or who are known to be human immunodeficiency virus (HIV) positive 7. Severe renal dysfunction (estimated glomerular filtration rate at the Screening visit; calculated by the central laboratory)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary efficacy measure is Hb response., defined as increase of Hb from baseline by > 1 g/dL at 24 weeks. Hb at 24 weeks is determined by the average value of Hb levels at Week 20 and Week 24. | — |
Secondary
| Measure | Time frame |
|---|---|
| The secondary efficacy endpoints are as follows: · Change from baseline in hemoglobin at Week 24 · Change and percent change from baseline in hemolysis measures, including unconjugated bilirubin, absolute reticulocyte, reticulocytes %, and LDH at Week 24 · Incidence of severe anemic episodes (Hb | — |
Countries
Belgium, Canada, Egypt, France, Germany, Ghana, Italy, Jamaica, Kenya, Lebanon, Netherlands, Nigeria, Oman, Qatar, Turkey, United Kingdom, United States of America
Outcome results
None listed