A Dose-Finding Study of Tebapivat to Assess Efficacy, and Safety in Participants With Sickle Cell Disease (SCD)

Phase 2

Recruiting

• Conditions: Sickle Cell Disease
• Interventions: Drug: Tebapivat; Drug: Tebapivat Matched Placebo

• Registration Number: NCT06924970
• Lead Sponsor: Agios Pharmaceuticals, Inc.

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2025-04-10
• Study First Submitted QC: 2025-04-10
• Study First Posted: 2025-04-13
• Study Start: 2025-05-01
• Status Verified: 2025-06
• Last Update Submitted: 2025-06-19
• Last Update Posted: 2025-06-22
• Primary Completion: 2026-05
• Study Completion: 2027-05-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 56

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Tebapivat 2.5 milligrams (mg)	Tebapivat	Participants will receive 2.5 mg tebapivat orally, once daily (QD) for 12-weeks in the double-blind (DB) period. Participants who complete the DB Period will be eligible to receive the same dose in the Open-Label Extension (OLE) period for up to 52 weeks.
Tebapivat 5.0 mg	Tebapivat	Participants will receive 5.0 mg tebapivat orally, QD, for 12-weeks in the DB period. Participants who complete the DB Period will be eligible to receive the same dose in the OLE period for up to 52 weeks.
Tebapivat Matched Placebo	Tebapivat Matched Placebo	Participants will receive a matched placebo, orally, QD, for 12-weeks in the DB period. Participants who complete the DB Period will be randomized in 1:1:1 to receive tebapivat 2.5 mg QD, tebapivat 5.0 mg QD, or tebapivat 7.5 mg QD in the OLE period for up to 52 weeks
Tebapivat 7.5 mg	Tebapivat	Participants will receive 7.5 mg tebapivat orally, QD, for 12-weeks in the DB period. Participants who complete the DB Period will be eligible to receive the same dose in the OLE period for up to 52 weeks.
Tebapivat Matched Placebo	Tebapivat	Participants will receive a matched placebo, orally, QD, for 12-weeks in the DB period. Participants who complete the DB Period will be randomized in 1:1:1 to receive tebapivat 2.5 mg QD, tebapivat 5.0 mg QD, or tebapivat 7.5 mg QD in the OLE period for up to 52 weeks

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Hb Response	Baseline, Week 10 through Week 12

Secondary Outcome Measures

Name	Time	Method
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 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 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
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
Time to Cmax (tmax) of Tebapivat	Pre-dose and at multiple timepoints post-dose up to Week 8
Average Change From Baseline in Absolute Reticulocyte Count	Baseline, Week 10 through Week 12
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

Trial Locations

Locations (2)

MedStar Washington Hospital Center; 🇺🇸 Washington, District of Columbia, United States

Icahn School of Medicine at Mt. Sinai; 🇺🇸 New York, New York, United States