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

Agios Pharmaceuticals

Status and phase: Enrolling; Phase 2

Conditions: Sickle Cell Disease

Treatments: Drug: Tebapivat Matched Placebo; Drug: Tebapivat

Study type: Interventional

Funder types: Industry

Identifiers

NCT06924970

2024-519746-70-01 (EU Trial (CTIS) Number)

AG946-C-003

Details and patient eligibility

About

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.

Enrollment: 56 estimated patients

Sex: All

Ages: 16+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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56 participants in 4 patient groups, including a placebo group

Tebapivat 2.5 milligrams (mg)

Experimental group

Description:

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.

Treatment:

Drug: Tebapivat

Tebapivat 5.0 mg

Experimental group

Description:

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.

Treatment:

Drug: Tebapivat

Tebapivat 7.5 mg

Experimental group

Description:

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.

Treatment:

Drug: Tebapivat

Tebapivat Matched Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Tebapivat

Drug: Tebapivat Matched Placebo