Skip to content
Clinical Trials – home
Not recruitingRare disease

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

Verified siteInvestigational
Clinical Trials Concierge

Prefer not to search? Our Concierge searches the trials for you.

What is this trial about?

A plain-language summary of the goals, design and what participants do

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.

The research process

The trial runs in 8 steps – from screening to follow-up. Each step says what happens and what the team monitors.

  1. Step 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. Step 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. Step 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. Step 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. Step 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. Step 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. Step 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. Step 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 trial?

9 criteria

  • 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 trial?

12 criteria

  • 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
Clinical Trials Concierge

Prefer not to search? Our Concierge searches the trials for you.

Tell us about your condition – we search every trial in Europe and connect you with the right site.

We usually reply within a few days

Verified sites

All sites with verified contact details – recruitment status may not be available; ask directly

Trial locations

Where you can join this trial

Countries are shaded by recruitment status. Click a recruiting country to ask about joining there.

Not recruiting
Not finding your country?

Not sure what to do next?

Joining a clinical trial can seem overwhelming. We guide you step by step, so you know exactly what to expect and how we support you through the process.

See the full process and FAQ

Investigated drugs

  • 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.

What is already known about the treatment

Tebapivat – A medication being studied in clinical trials for sickle cell disease, administered orally to help improve anemia in affected patients. Tebapivat is an investigational drug that works by activating pyruvate kinase, an enzyme that may help increase the energy metabolism in red blood cells and potentially reduce sickling of these cells. The medication belongs to the class of pyruvate kinase activators and aims to address the underlying mechanisms of sickle cell disease rather than just managing symptoms. Currently, tebapivat is in Phase 2 clinical trials to determine its optimal dosing, safety profile, and effectiveness in improving hemoglobin levels in people with sickle cell disease.

Investigated diseases

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 detailsLast updated 7 Oct 2026
Age18+ yearsPhasePhase IITrial ID2024-519746-70-01Protocol codeAG946-C-003Estimated enrolment56 patientsSponsorAgios Pharmaceuticals Inc.

sourced from the EU Clinical Trials Register and site verification

Want to learn more about this trial or check if you can participate?

Clinical Trials Concierge

Prefer not to search? Our Concierge searches the trials for you.

Tell us about your condition – we search every trial in Europe and connect you with the right site.