Sickle Cell DiseasePhase 2NCT06924970
A Dose-Finding Study of Tebapivat to Assess Efficacy, and Safety in Participants With Sickle Cell Disease (SCD)
A Phase 2 study testing Tebapivat in people with Sickle Cell Disease, run by Agios Pharmaceuticals, Inc. at 20 sites in 7 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Sickle Cell Disease
- What is being tested?
- Tebapivat
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 59 participants
- Where
- 20 sitesin 7 countries
- Study dates
- 1 May 2025to May 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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 locations and contacts
20 sites in 7 countries.
20 sites in 7 countries
United States10 sites
Emory-Children's Center/ Children's Healthcare of Atlanta: Arthur M. Blank Hospital
Atlanta, Georgia, 30322
Henry Ford Health System
Detroit, Michigan, 48202
Children's Hospital of Michigan
Detroit, Michigan, 48304
UConn Health
Farmington, Connecticut, 06030-0001
Prisma Health Cancer Institute - Farris Road
Greenville, South Carolina, 29605
University of Texas Health Science Center of Houston
Houston, Texas, 77030
Icahn School of Medicine at Mt. Sinai
New York, New York, 10029
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15232
Fred Hutchinson Cancer Center, University of Washington
Seattle, Washington, 98195
MedStar Washington Hospital Center
Washington D.C., District of Columbia, 20010
France3 sites
CHU Hôpital Henri Mondor
Créteil, Île-de-France Region, 94010
Hôpital Edouard Herriot, CHU de Lyon
Lyon, Auvergne-Rhône-Alpes, 69003
Institut Universitaire du Cancer de Toulouse - Oncopole
Toulouse, Midi Pyrenees, 31059
Netherlands3 sites
Amsterdam Universitair Medisch Centrum, Locatie AMC
Amsterdam, North Holland, 1105AZ
Erasmus MC
Rotterdam, South Holland, 3015 GD
Universitair Medisch Centrum Utrecht
Utrecht, 3584 CX
About this study
Official title: 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.
- Conditions
- Sickle Cell Disease
- Being tested
- Tebapivat, Tebapivat Matched Placebo
- Medical subject headings
- Anemia, Sickle Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TebapivatDrug
Also called AG-946
Oral tablets.
Tebapivat Matched PlaceboDrug
Oral tablets.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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 Receives: Drug: Tebapivat; Drug: Tebapivat Matched Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Hb Response
Measured: Baseline, Week 10 through Week 12
Secondary outcomes (16)
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Measured: Up to Week 72
Average Change From Baseline in Hb Concentration
Measured: Baseline, Week 10 through Week 12
Average Change From Baseline in Indirect Bilirubin
Measured: Baseline, Week 10 through Week 12
Average Change From Baseline in Lactate Dehydrogenase (LDH)
Measured: Baseline, Week 10 through Week 12
Average Change From Baseline in Absolute Reticulocyte Count
Measured: Baseline, Week 10 through Week 12
Average Change From Baseline in Percent Reticulocytes
Measured: Baseline, Week 10 through Week 12
Average Change From Baseline in Erythropoietin
Measured: Baseline, Week 10 through Week 12
Average Change From Baseline in Patient Reported Outcomes Measurement Information System® (PROMIS) Fatigue 13a Short Form Score
Measured: Baseline, Week 10 through Week 12
Average Change From Baseline in PROMIS Pain Intensity 1a Score
Measured: 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
Measured: Baseline, Week 10 through Week 12
Plasma Concentration of Tebapivat
Measured: Pre-dose and at multiple timepoints post-dose up to Week 8
Maximum (Peak) Concentration (Cmax) of Tebapivat
Measured: Pre-dose and at multiple timepoints post-dose up to Week 8
Time to Cmax (tmax) of Tebapivat
Measured: 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
Measured: Pre-dose and at multiple timepoints post-dose up to Week 8
Whole Blood Concentrations of 2,3-Diphosphoglycerate (2,3-DPG)
Measured: Pre-dose and at multiple timepoints post-dose up to Week 8
Whole Blood Concentrations of Adenosine Triphosphate (ATP)
Measured: Pre-dose and at multiple timepoints post-dose up to Week 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Apr 2025
- Study start1 May 2025
- Primary completion12 May 2026
- Study completionMay 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
- More trials run by Agios Pharmaceuticals, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 59 participants (actual)
Sponsor and investigators
- Lead sponsor
- Agios Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06924970
- Sponsor's protocol ID
- AG946-C-003
- Other IDs
- 2024-519746-70-01
- Status last verified
- Oct 2026
- First submitted
- 10 Apr 2025
- Last updated
- 28 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Double-blind, Randomized, Placebo-Controlled, Multicenter, Dose- Finding, Efficacy, and Safety Study of Tebapivat in Participants With Sickle Cell Disease
- ClinicalTrials.gov ID
- NCT06924970
- Acronym / sponsor ID
- AG946-C-003
- Conditions
- Sickle Cell Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 59 participants (actual)
- Lead sponsor
- Agios Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 1 May 2025 (actual)
- Primary completion
- 12 May 2026 (actual)
- Study completion
- May 2027 (estimated)
- First posted
- 13 Apr 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Tebapivat 2.5 milligrams (mg) | Experimental | Drug: TebapivatParticipants 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. |
| Tebapivat 5.0 mg | Experimental | Drug: TebapivatParticipants 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. |
| Tebapivat 7.5 mg | Experimental | Drug: TebapivatParticipants 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. |
| Tebapivat Matched Placebo | Placebo comparator | Drug: Tebapivat, Drug: Tebapivat Matched PlaceboParticipants 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 |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- 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 (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TebapivatAlso: AG-946Oral tablets. | Drug | Tebapivat 2.5 milligrams (mg), Tebapivat 5.0 mg, Tebapivat 7.5 mg, Tebapivat Matched Placebo |
| Tebapivat Matched PlaceboOral tablets. | Drug | Tebapivat Matched Placebo |
Primary outcome
Percentage of Participants With Hb Response
Time frame: Baseline, Week 10 through Week 12
16 secondary outcomes
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Up to Week 72
Average Change From Baseline in Hb Concentration
Time frame: Baseline, Week 10 through Week 12
Average Change From Baseline in Indirect Bilirubin
Time frame: Baseline, Week 10 through Week 12
Average Change From Baseline in Lactate Dehydrogenase (LDH)
Time frame: Baseline, Week 10 through Week 12
Average Change From Baseline in Absolute Reticulocyte Count
Time frame: Baseline, Week 10 through Week 12
Average Change From Baseline in Percent Reticulocytes
Time frame: Baseline, Week 10 through Week 12
Average Change From Baseline in Erythropoietin
Time frame: Baseline, Week 10 through Week 12
Average Change From Baseline in Patient Reported Outcomes Measurement Information System® (PROMIS) Fatigue 13a Short Form Score
Time frame: Baseline, Week 10 through Week 12
Average Change From Baseline in PROMIS Pain Intensity 1a Score
Time frame: 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
Time frame: Baseline, Week 10 through Week 12
Plasma Concentration of Tebapivat
Time frame: Pre-dose and at multiple timepoints post-dose up to Week 8
Maximum (Peak) Concentration (Cmax) of Tebapivat
Time frame: Pre-dose and at multiple timepoints post-dose up to Week 8
Time to Cmax (tmax) of Tebapivat
Time frame: 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
Time frame: Pre-dose and at multiple timepoints post-dose up to Week 8
Whole Blood Concentrations of 2,3-Diphosphoglycerate (2,3-DPG)
Time frame: Pre-dose and at multiple timepoints post-dose up to Week 8
Whole Blood Concentrations of Adenosine Triphosphate (ATP)
Time frame: Pre-dose and at multiple timepoints post-dose up to Week 8
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Oct 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
20 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tebapivat in people with Sickle Cell Disease, run by Agios Pharmaceuticals, Inc. at 20 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 28 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in United States, France, Netherlands, Belgium, Canada and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Hb Response (time frame: Baseline, Week 10 through Week 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Oct 2026.