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

NCT06924970 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: AG946-C-0032024-519746-70-01
• Study Type: interventional
• Target: 59
• Locations: 7 countries
• Sites: 30

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.

Conditions

Sickle Cell Disease

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Hb Response

  Baseline, Week 10 through Week 12

Secondary Outcomes (16)

• 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

Study Arms (4)

Tebapivat 2.5 milligrams (mg)

EXPERIMENTAL

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

Tebapivat 5.0 mg

EXPERIMENTAL

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

Tebapivat 7.5 mg

EXPERIMENTAL

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

Tebapivat Matched Placebo

PLACEBO COMPARATOR

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; Drug: Tebapivat Matched Placebo

Interventions

Tebapivat DRUG

Oral tablets.

Also known as: AG-946

Tebapivat 2.5 milligrams (mg); Tebapivat 5.0 mg; Tebapivat 7.5 mg; Tebapivat Matched Placebo

Tebapivat Matched Placebo DRUG

Oral tablets.

Tebapivat Matched Placebo

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Agios Pharmaceuticals, Inc.: lead

Study Sites (30)

UCHealth at University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

UConn Health

Farmington, Connecticut, 06030-0001, United States

Location

Children's National Hospital

Washington D.C., District of Columbia, 20010, United States

Location

MedStar Washington Hospital Center

Washington D.C., District of Columbia, 20010, United States

Location

Emory-Children's Center/ Children's Healthcare of Atlanta: Arthur M. Blank Hospital

Atlanta, Georgia, 30322, United States

Location

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

Boston Medical Center & Boston University School of Medicine

Boston, Massachusetts, 02118, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Children's Hospital of Michigan

Detroit, Michigan, 48304, United States

Location

Icahn School of Medicine at Mt. Sinai

New York, New York, 10029, United States

Location

Montefiore Medical Center

The Bronx, New York, 10460, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Lifespan at Rhode Island Hospital

Providence, Rhode Island, 02903-4923, United States

Location

Prisma Health Cancer Institute - Farris Road

Greenville, South Carolina, 29605, United States

Location

University of Texas Health Science Center of Houston

Houston, Texas, 77030, United States

Location

Fred Hutchinson Cancer Center, University of Washington

Seattle, Washington, 98195, United States

Location

CHR de la Citadelle

Liège, Wallonne, 4000, Belgium

Location

Clinique CHC MontLégia

Liège, Wallonne, 4420, Belgium

Location

CHU Montreal

Montreal, Quebec, H2X 3E4, Canada

Location

Hôpital Edouard Herriot, CHU de Lyon

Lyon, Auvergne-Rhône-Alpes, 69003, France

Location

Institut Universitaire du Cancer de Toulouse - Oncopole

Toulouse, Midi Pyrenees, 31059, France

Location

CHU Hôpital Henri Mondor

Créteil, Île-de-France Region, 94010, France

Location

St. James Hospital

Dublin, Leinster, D08 A978, Ireland

Location

Amsterdam Universitair Medisch Centrum, Locatie AMC

Amsterdam, North Holland, 1105AZ, Netherlands

Location

Erasmus MC

Rotterdam, South Holland, 3015 GD, Netherlands

Location

Universitair Medisch Centrum Utrecht

Utrecht, 3584 CX, Netherlands

Location

Evelina London Children's Hospital, Guy's and St. Thomas' NHS Foundation Trust

London, SE5 9RS, United Kingdom

Location

Kings College Hospital NHS Foundation Trust

London, SE5 9RS, United Kingdom

Location

University College London

London, WC1E 6BT, United Kingdom

Location

MeSH Terms

Conditions

Anemia, Sickle Cell

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 10, 2025
• First Posted: April 13, 2025
• Study Start: May 1, 2025
• Primary Completion: May 1, 2026
• Study Completion (Estimated): May 1, 2027
• Last Updated: April 23, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (3); NL (3); GB (3); IE (1); BE (2); US (17); CA (1)