Study on the Effects of Tebapivat and AG-946 in Patients with Sickle Cell Disease

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What is this study about?

This clinical trial is studying Tebapivat for the treatment of Sickle Cell Disease (SCD). Sickle Cell Disease is a group of inherited blood disorders where red blood cells become crescent or sickle-shaped instead of round, which can lead to blocked blood flow, pain, infections, and anemia (low red blood cell count). The purpose of this study is to compare different doses of Tebapivat versus placebo to determine its effect on anemia in people with Sickle Cell Disease.

The study is designed to find the optimal dose of Tebapivat by measuring its impact on hemoglobin levels (the protein in red blood cells that carries oxygen) and other markers of blood health. Participants will take either Tebapivat or placebo for 12 weeks during the initial double-blind period. During this time, researchers will monitor changes in hemoglobin concentration, markers of red blood cell breakdown (hemolysis), and how participants feel regarding fatigue and pain.

After the initial 12-week period, participants may continue in an open-label extension period where all participants receive Tebapivat. Throughout the study, participants will undergo various assessments including blood tests, questionnaires about pain and quality of life, and tests measuring physical and cognitive function. The study will also evaluate the safety of Tebapivat by monitoring any side effects that occur during treatment.

1 Study Introduction

This is a Phase 2 clinical trial studying tebapivat (also called AG-946) in patients with Sickle Cell Disease (SCD). The trial will assess different doses to determine how effectively tebapivat treats anemia compared to placebo.

The study is designed as a double-blind trial, which means neither you nor the study doctors will know whether you are receiving tebapivat or placebo until the study is complete.

2 Screening Period

Before starting treatment, you will undergo screening to confirm eligibility. This includes at least two hemoglobin measurements taken at least 7 days apart.

Your hemoglobin level must be between 5.5 and 10.5 g/dL to participate in the study.

If you are currently taking hydroxyurea, your dose must have been stable for at least 90 days before randomization. If you recently stopped taking hydroxyurea, there must be a 90-day washout period before you can provide consent.

3 Randomization

After confirming your eligibility, you will be randomly assigned to receive either tebapivat or a placebo.

The medication comes in the form of coated tablets that you will take orally according to the dosing schedule determined by your study group.

4 Double-blind Treatment Period

This initial treatment period lasts 12 weeks.

You will take the assigned study medication (either tebapivat or placebo) as directed by the study team.

Throughout this period, your hemoglobin levels and other blood markers will be regularly monitored.

At Week 8, blood samples will be collected to evaluate biomarkers related to inflammation, vascular biology, and SCD pathogenesis.

At Week 10, blood samples will be collected to evaluate biomarkers related to iron metabolism.

Between Weeks 10-12, your response to treatment will be assessed, with the primary goal being to see if your hemoglobin has increased by at least 1.0 g/dL from your baseline level.

5 Assessment Procedures

Throughout the study, you will complete several questionnaires about your fatigue levels, pain intensity, and quality of life.

At Week 12, you will perform a 6-Minute Walk Test (6MWT), which measures how far you can walk in 6 minutes.

You will also complete cognitive tests including the Identification Test, One Back Test, and Groton Maze Learning Test.

A Work Productivity and Activity Impairment (WPAI) assessment will be conducted to measure how your condition affects your ability to work and perform regular activities.

6 Safety Monitoring

Throughout the study, you will be monitored for any side effects or adverse events.

Blood samples will be collected to measure the concentration of tebapivat in your system and to evaluate its effects on certain blood components like 2,3-DPG (2,3-diphosphoglycerate) and ATP (adenosine triphosphate).

The study will track any Sickle Cell Pain Crises (SCPCs) you experience during the 12-week period.

7 Open-label Extension Period

After completing the initial 12-week double-blind period, you may have the option to enter an Open-label Extension (OLE) Period.

During this extension, all participants receive tebapivat (no placebo).

The study will continue to monitor changes in your hemoglobin concentration, markers of erythropoiesis (red blood cell production) and hemolysis (red blood cell breakdown), patient-reported outcomes, and biomarkers.

Safety monitoring will continue throughout this extension period.

8 Study Completion

The anticipated study completion date is September 30, 2027, though individual participation may vary.

After completing the study, you will have a follow-up assessment to evaluate your overall health and any lasting effects from the treatment.

Who Can Join the Study?

You must be at least 16 years old to join the study (at least 18 years old if in France)
You must have a confirmed diagnosis of sickle cell disease (a blood disorder that affects the shape of red blood cells)
Your hemoglobin (protein in red blood cells that carries oxygen) level must be between 5.5 and 10.5 g/dL, measured at least twice during screening
If you’re taking hydroxyurea (a medication for sickle cell disease), your dose must have been stable for at least 90 days before starting the study
If you stopped taking hydroxyurea, you must have been off it for at least 90 days before joining the study
Women who can become pregnant must either abstain from sexual activities or use highly effective birth control methods throughout the study and for 28 days after
Men with partners who can become pregnant must either abstain from sexual activities or use condoms throughout the study and for 28 days after
You must be willing to provide written informed consent (agreement) to participate
For participants under 18 years old: your parent or legal guardian must also provide consent for your participation

Who Cannot Join the Study?

If you have sickle cell disease types other than hemoglobin SS (HbSS) or hemoglobin Sβ0 thalassemia (HbSβ0)
If you have had a blood transfusion in the past 90 days
If you are pregnant or breastfeeding
If you have severe kidney disease
If you have active liver disease (problems with liver function)
If you have a history of high blood pressure that is not well controlled
If you are taking hydroxyurea (a medication for sickle cell disease) and have not been on a stable dose for at least 90 days
If you are currently participating in another clinical trial
If you have had a vaso-occlusive crisis (painful episode when blood vessels get blocked by sickle cells) that required medical care within 30 days before starting the study
If you have been hospitalized for complications of sickle cell disease within 30 days before starting the study
If you have a history of substance abuse in the past year
If you have serious mental health conditions that might interfere with your participation

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country	Status
Oncopole Claudius Regaud	Toulouse	France

Other Sites

Site Name	City	Country
Centre Hospitalier Regional De La Citadelle	Liege	Belgium
Hospital Edouard Herriot	Lyon	France
Universitair Medisch Centrum Utrecht	Utrecht	The Netherlands
Hopital Beaujon	Clichy	France
Apkhtdqmc Uiu	Amsterdam	The Netherlands
Ezzmqkw Urtdsllwauen Mbgknby Cwhxelz Rfzmzyysa (rccqevp Mqq	Rotterdam	The Netherlands
Hxrqdol Hogwo Mdintg &msiqcq 1 rgx Guavkhh Ewjptt	Creteil	France

Trial status

Country	Status	Recruitment Start
Belgium	Not recruiting	01.07.2025
France	Not recruiting	01.07.2025
Ireland	Not recruiting	01.07.2025
The Netherlands	Not recruiting	01.07.2025

Trial locations

Tebapivat is a medication being studied for people with sickle cell disease. It is being tested to see if it can help improve anemia (low red blood cell count) in patients with this condition. The study is looking at how different doses of the medication affect hemoglobin levels, which is the protein in red blood cells that carries oxygen throughout the body.

Placebo is an inactive substance that looks like the real treatment but has no medical effect. It’s used as a comparison to see if the active medication (tebapivat) works better than no treatment at all.

Investigated diseases:

Sickle cell disease

Sickle Cell Disease – A genetic blood disorder characterized by abnormal, sickle-shaped red blood cells. These irregularly shaped cells can block blood vessels, reducing blood flow and oxygen delivery to tissues. The disease causes anemia due to the premature destruction of red blood cells, a process called hemolysis. Patients typically experience episodes of severe pain called sickle cell pain crises, which occur when blood flow is obstructed. Over time, the condition can affect multiple organs including the lungs, kidneys, spleen, and brain. The disease is present from birth and is caused by mutations in the gene that produces hemoglobin, the protein that carries oxygen in red blood cells.

Trial ID:

2024-519746-70-01

Protocol code:

AG946-C-003

Trial Phase:

Therapeutic exploratory (Phase II)

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Study on the Effects of Tebapivat and AG-946 in Patients with Sickle Cell Disease

What is this study about?

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Who Cannot Join the Study?