Sickle Cell Disease
Conditions
Brief summary
The main purpose of this study is to compare the effect of tebapivat versus placebo on anemia and to detect a dose-response for hemoglobin (Hb) response in participants with SCD.
Interventions
DRUGTebapivat
Oral tablets.
DRUGTebapivat Matched Placebo
Oral tablets.
Sponsors
Agios Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Documented diagnosis of SCD (HbSS, HbSC \[combined heterozygosity for hemoglobins S and C\], sickle hemoglobin \[HbS\]/β0-thalassemia, HbS/β+-thalassemia, or other sickle cell syndrome variants). * Hemoglobin ≥5.5 and ≤10.5 grams per decilitre (g/dL). Hemoglobin concentration must be based on an average of at least 2 Hb concentration measurements (separated by ≥7 days) collected during the screening period. * If taking hydroxyurea, the hydroxyurea dose must be stable for at least 90 days before randomization. Discontinuation of hydroxyurea requires a 90-day washout before providing informed consent. Key
Exclusion criteria
* Receiving regularly scheduled red blood cell (RBC) transfusion therapy (also termed chronic, prophylactic, or preventative transfusion); episodic transfusion in response to worsened anemia or vaso-occlusive crisis (VOC) is permitted. Additionally, a participant who requires episodic transfusion(s) may not have received a transfusion(s) within 60 days before providing informed consent or during the screening period. * \>10 sickle cell pain crisis (SCPCs) in the 12 months before providing informed consent. * Receiving anabolic steroids that have not been stopped for at least 4 weeks before randomization. Testosterone replacement therapy to treat hypogonadism is allowed; the testosterone dose and preparation must be stable for ≥10 weeks before randomization. * Hospitalized for an SCPC and/or other vaso-occlusive event within 14 days before providing informed consent or within 14 days before randomization. If an SCPC occurs during the screening period, the screening period may be extended with Medical Monitor approval. * Receiving treatment with voxelotor, crizanlizumab, or L-glutamine within 90 days before randomization. * Platelet count \<lower limit of normal (LLN) for the local laboratory or \<150×109/liter (L) (whichever is lower) during screening. Platelet transfusions received within 28 days before consent or during screening. * Receiving treatment with hematopoietic stimulating agents within 90 days before randomization. * Prior exposure to gene therapy or prior bone marrow or stem cell transplantation, including any conditioning regimen.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of Participants With Hb Response | Baseline, Week 10 through Week 12 |
Secondary
| Measure | Time frame |
|---|---|
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Up to Week 72 |
| Average Change From Baseline in Hb Concentration | Baseline, Week 10 through Week 12 |
| Average Change From Baseline in Indirect Bilirubin | Baseline, Week 10 through Week 12 |
| Average Change From Baseline in Lactate Dehydrogenase (LDH) | Baseline, Week 10 through Week 12 |
| Average Change From Baseline in Absolute Reticulocyte Count | Baseline, Week 10 through Week 12 |
| Average Change From Baseline in Percent Reticulocytes | Baseline, Week 10 through Week 12 |
| Average Change From Baseline in Erythropoietin | Baseline, Week 10 through Week 12 |
| Average Change From Baseline in Patient Reported Outcomes Measurement Information System® (PROMIS) Fatigue 13a Short Form Score | Baseline, Week 10 through Week 12 |
| Average Change From Baseline in PROMIS Pain Intensity 1a Score | Baseline, Week 10 through Week 12 |
| Average Change From Baseline in Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me) Pain Impact Score | Baseline, Week 10 through Week 12 |
| Plasma Concentration of Tebapivat | Pre-dose and at multiple timepoints post-dose up to Week 8 |
| Maximum (Peak) Concentration (Cmax) of Tebapivat | Pre-dose and at multiple timepoints post-dose up to Week 8 |
| Time to Cmax (tmax) of Tebapivat | Pre-dose and at multiple timepoints post-dose up to Week 8 |
| Area Under the Concentration-time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUC0-t) of Tebapivat | Pre-dose and at multiple timepoints post-dose up to Week 8 |
| Whole Blood Concentrations of 2,3-Diphosphoglycerate (2,3-DPG) | Pre-dose and at multiple timepoints post-dose up to Week 8 |
| Whole Blood Concentrations of Adenosine Triphosphate (ATP) | Pre-dose and at multiple timepoints post-dose up to Week 8 |
Countries
Belgium, Canada, France, Ireland, Netherlands, United Kingdom, United States
Outcome results
None listed