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

A Phase 2, Double-blind, Randomized, Placebo-Controlled, Multicenter, Dose- Finding, Efficacy, and Safety Study of Tebapivat in Participants With Sickle Cell Disease

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Sickle Cell Disease
• Intervention / Treatment: Drug: Tebapivat; Drug: Tebapivat Matched Placebo

• Study Type: Interventional
• Enrollment (Actual): 59
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Wallonne
    • Liège, Wallonne, Belgium, 4000
      • CHR de la Citadelle
    • Liège, Wallonne, Belgium, 4420
      • Clinique CHC MontLégia
• Canada
  • Quebec
    • Montreal, Quebec, Canada, H2X 3E4
      • CHU Montreal
• France
  • Auvergne-Rhône-Alpes
    • Lyon, Auvergne-Rhône-Alpes, France, 69003
      • Hopital Edouard Herriot, CHU de Lyon
  • Midi Pyrenees
    • Toulouse, Midi Pyrenees, France, 31059
      • Institut Universitaire du Cancer de Toulouse - Oncopole
  • Île-de-France Region
    • Créteil, Île-de-France Region, France, 94010
      • CHU Hôpital Henri Mondor
• Ireland
  • Leinster
    • Dublin, Leinster, Ireland, D08 A978
      • St. James Hospital
• Netherlands
  • Utrecht, Netherlands, 3584 CX
    • Universitair Medisch Centrum Utrecht
  • North Holland
    • Amsterdam, North Holland, Netherlands, 1105AZ
      • Amsterdam Universitair Medisch Centrum, Locatie AMC
  • South Holland
    • Rotterdam, South Holland, Netherlands, 3015 GD
      • Erasmus MC
• United Kingdom
  • London, United Kingdom, SE5 9RS
    • Kings College Hospital NHS Foundation Trust
  • London, United Kingdom, WC1E 6BT
    • University College London
  • London, United Kingdom, SE5 9RS
    • Evelina London Children's Hospital, Guy's and St. Thomas' NHS Foundation Trust
• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • UCHealth at University of Colorado Anschutz Medical Campus
  • Connecticut
    • Farmington, Connecticut, United States, 06030-0001
      • UConn Health
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20010
      • Children's National Hospital
    • Washington D.C., District of Columbia, United States, 20010
      • Medstar Washington Hospital Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory-Children's Center/ Children's Healthcare of Atlanta: Arthur M. Blank Hospital
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann & Robert H. Lurie Children's Hospital of Chicago
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center & Boston University School of Medicine
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
    • Detroit, Michigan, United States, 48304
      • Children's Hospital of Michigan
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mt. Sinai
    • The Bronx, New York, United States, 10460
      • Montefiore Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Medical Center
  • Rhode Island
    • Providence, Rhode Island, United States, 02903-4923
      • Lifespan at Rhode Island Hospital
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Prisma Health Cancer Institute - Farris Road
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas Health Science Center of Houston
  • Washington
    • Seattle, Washington, United States, 98195
      • Fred Hutchinson Cancer Center, University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tebapivat 2.5 milligrams (mg); 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.	Drug: Tebapivat; Oral tablets.; Other Names: AG-946
Experimental: Tebapivat 5.0 mg; 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.	Drug: Tebapivat; Oral tablets.; Other Names: AG-946
Experimental: Tebapivat 7.5 mg; 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.	Drug: Tebapivat; Oral tablets.; Other Names: AG-946
Placebo Comparator: 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	Drug: Tebapivat; Oral tablets.; Other Names: AG-946; Drug: Tebapivat Matched Placebo; Oral tablets.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of Participants With Hb Response	Baseline, Week 10 through Week 12

Secondary Outcome Measures

Outcome 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

Collaborators and Investigators

• Sponsor: Agios Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2025
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: April 10, 2025
• First Submitted That Met QC Criteria: April 10, 2025
• First Posted (Actual): April 13, 2025

Study Record Updates

• Last Update Posted (Actual): May 29, 2026
• Last Update Submitted That Met QC Criteria: May 28, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; Anemia, Sickle Cell
• Other Study ID Numbers: AG946-C-003; 2024-519746-70-01 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No