Sickle Cell Disease MedDRA version: 21.0 Level: PT Classification code 10040644 Term: Sickle cell disease System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: Voxelotor 500 mg
Product Code: GBT440
Pharmaceutical Form: Tablet
INN or Proposed INN: VOXELOTOR
CAS Number: 1446321-46-5
Current Sponsor code: GBT440
Concentration unit: mg milligram(s)
Sponsors
Global Blood Therapeutics, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Participants who meet all the following criteria will be eligible for enrollment in the study: 1. Male or female with sickle cell disease 2. Documentation of SCD genotype HbSS or HbSB0 3. Age 18 to =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Participants meeting any of the following exclusion criteria will not be eligible for study enrollment: 1. More than 10 vaso-occlusive crises (VOCs) within 12 months of screening that required a hospital, emergency room, or clinic visit 2. Female participant who is breast feeding or pregnant 3. Receiving regularly scheduled blood (red blood cell [RBC]) transfusion therapy (also termed chronic, prophylactic, or preventive transfusion) or have received an RBC transfusion for any reason within 60 days of signing the ICF or at any time during the screening period 4. Hospitalized for sickle cell crisis or other vaso-occlusive event within 30 days prior to dosing (ie, a vaso-occlusive event cannot be within 30 days prior to dosing) 5. Screening laboratory test of alanine aminotransferase (ALT) > 4 × upper level of normal (ULN) 6. Clinically significant bacterial, fungal, parasitic, or viral infection which requires therapy, including acute bacterial infection requiring antibiotics 7. Known to be COVID-19 positive from within 3 weeks of screening through Day 1 8. Participants with known active hepatitis A, B, or C or who are known to be human immunodeficiency virus (HIV) positive 9. Severe renal dysfunction (estimated glomerular filtration rate [GFR] 220 msec in any participant b. QRS interval > 120 msec or QT interval corrected using Fridericia’s formula (QTcF) > 480 msec (both genders) in participants without bundle branch block c. QRS interval > 120 msec in participants with newly (within 3 months) emerged bundle branch block d. A participant with stable bundle branch block with or without stable cardiac disease may be enrolled; QRS interval > 120 msec and QTcF interval > 480 msec are acceptable in these participants. 13. Any condition affecting drug absorption, such as major surgery involving the stomach or small intestine (prior cholecystectomy is acceptable) 14. Participated in another clinical trial of an investigational agent or medical device within 30 days or 5 half-lives of date of informed consent, whichever is longer, or is currently participating in another trial of an investigational agent or medical device 15. Inadequate venous access as determined by the Investigator/site staff 16. Medical, psychological, or behavioral conditions, which, in the opinion of the investigator, may preclude safe participation, confound study interpretation, interfere with compliance, or preclude informed consent 17. Received erythropoietin or other hematopoietic growth factor treatment within 28 days of signing ICF or is anticipated to require such agents during the study 18. Ongoing or recent (within 2 years) substance abuse 19. Known allergy to voxelotor 20. Use of herbal medications (eg, St. John’s Wort), se
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the tolerability and safety of voxelotor at daily doses of >1500 mg (2000 mg to 3000 mg) in participants with sickle cell disease (SCD);Secondary Objective: Secondary Objectives: - To evaluate the change in Hb and hemolysis measures - To evaluate the incidence rate of vaso-occlusive crises (VOCs) Exploratory Objectives: - To evaluate the pharmacodynamic (PD) properties (effect on Hb-oxygen equilibrium curve [OEC]) as measured by P50 and P20 - To assess voxelotor pharmacokinetics (PK) as evaluated by population PK analysis and % Hb occupancy - To evaluate the PK-PD relationship of voxelotor at daily doses of >1500 mg - To evaluate the effects of voxelotor on Clinical Global Impression of Change (CGI-C) and Patient Global Impression of Change (PGI-C) ;Primary end point(s): Treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs);Timepoint(s) of evaluation of this end point: Any new or worsening events which occurs after first dose or through 28 days after study drug discontinuation | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Endpoints: The secondary endpoints are: • Change in Hb and clinical measures of hemolysis (unconjugated bilirubin, % reticulocyte, absolute reticulocyte, and LDH) from Baseline • Proportion of participants with an Hb increase > 1 g/dL compared to Baseline • Incidence rate of VOCs Exploratory Endpoints: The exploratory endpoints are: • P50 and P20 at 8 hours and 24 hours postdose • PK of voxelotor as assessed by population PK analysis using nonlinear mixed-effect modeling • % Hb occupancy at 8 hours and 24 hours postdose • CGI-C • PGI-C;Timepoint(s) of evaluation of this end point: For the timepoints for the evaluation of the Secondary Endpoints and Exploratory Endpoints, please refer to the Schedule of assessment Appendix A- E in the GBT440-029 Study Protocol Amendment 2.0, dated 05 October 2020 | — |
Countries
United Kingdom
Contacts
Public ContactShaimaa Shafie
Global Blood Therapeutics, Inc.
Outcome results
None listed