Sickle Cell DiseasePhase 2HIBISCUS 3NCT05953584
A Phase 2 Open-label Study to Evaluate the Activity of Etavopivat on Transcranial Doppler Velocities in Pediatric Patients With Sickle Cell Disease Who Are at Increased Risk for Primary Stroke
A Phase 2 study testing Etavopivat and Hydroxyurea in people with Sickle Cell Disease, run by Forma Therapeutics, Inc. at 9 sites in 3 countries.
Trial summary
The study will test a new medicine, etavopivat, for sickle cell disease and see if it is safe and help-ful for participants with sickle cell disease who are at an increased risk of stroke. Read more about this study
- Who is it for?
- Ages 12 to 16 years
- Conditions the study is for
- Sickle Cell Disease
- What is being tested?
- Etavopivat and Hydroxyurea
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 9 sitesin 3 countries
- Study dates
- 20 Jun 2023to 28 Jun 2028
- 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 12 to 16 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Patient's parent, legal guardian, or legal representative has provided documented informed consent and patients have provided age-appropriate assent
- Age:
- 12 to 16 years of age (inclusive) at time of screening
- Type of Participant and Disease Characteristics:
- Confirmed diagnosis of SCD
- Documentation of any SCD genotype (e.g. HbSS, HbSβ0 -thalassemia) based on prior history of laboratory testing. Molecular genotyping is not required. SCD genotype may be determined from the results of Hb electrophoresis, high-performance liquid chromatography, or similar testing.
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- TAMMV greater than or equal to (≥) 170 cm/s in the ICA and/or MCA during the Screening Period and confirmed on 2 occasions and without history of primary ischemic or hemorrhagic stroke, transient ischemic attack, or severe central nervous system (CNS) vasculopathy on magnetic resonance angiography (MRA). This includes patients with cTCD (170-199 centimeter per second [cm/s]) or aTCD (≥ 200 cm/s). Patients with aTCD cohort must have refused transfusion therapy.
- Hb ≥ 6 grams per deciliter (g/dL) and lesser than or equal to (≤) 9 g/dL at screening
- For participants with aTCD and cTCD and already taking HU, the dose of HU milligram per kilogram (mg/kg) must be stable (no more than a 20% change in dosing except for weight-based changes) for at least 90 days prior to start of study treatment with no anticipated need for dose adjustments except for weight-based changes during the study, in the opinion of the Investigator.
- Sex and Contraceptive Requirements
- Patients, who if female and of childbearing potential, are using acceptable methods of contraception and agree not to donate ova from study start to 90 days after the last dose of study drug, and who if male, are willing to use acceptable methods of contraception and agree not to donate sperm, from study start to 90 days after the last dose of study drug
Who cannot join
- Medical Conditions
- Female who is breast feeding or pregnant
- History of seizure disorder
- Prior overt stroke (a focal neurological deficit of acute onset) by history or significant concerns for history of overt stroke based on Screening MRL, history of transient ischemic attack, focal neurological deficit on standardized neurological examination, or concern for moderate or severe neurological deficit (which could be due to stroke) based on a positive "10 questions" screening. Patients with significant or suggestive severe CNS vasculopathy (ie, moya moya) of Grade 4 or higher based on MRA read locally.
- Significant cytopenias (absolute neutrophil count [ANC] < 1.5 × 10^3/microliter (µL), platelets < 150,000/µL, reticulocytes < 80,000/µL)
- Severe renal dysfunction (estimated glomerular filtration rate at the Screening visit; calculated by the local laboratory < 30 mL/min/1.73 m^2) or on chronic dialysis
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- Hepatic dysfunction characterized by alanine aminotransferase (ALT) > 4 × upper limit of normal (ULN) and/or direct bilirubin > 3 × ULN
- Patients with clinically significant bacterial, fungal, parasitic, or viral infection requiring systemic therapy or history of such infections leading to significant neurological impairment:
- Patients with acute bacterial, fungal, parasitic, or viral infection requiring systemic therapy should delay screening/enrollment until active therapy has been completed.
- Patients with acute viral infections (eg, coronavirus disease 2019 [COVID-19]) should delay screening/enrollment until the acute infection has resolved.
- Patients enrolled in areas where malaria is prevalent must be on malaria prophylaxis based on regional guidance and resistance results. Note: Infection prophylaxis is allowed (see concomitant medication restrictions).
- Known human immunodeficiency virus (HIV) positivity
- Known infection with hepatitis B virus (hepatitis B surface antigen [HepBsAg] and hepatitis B core antibody [HepBcAb] positive.
Trial locations and contacts
9 sites in 3 countries. Contact the study team or a site near you to ask about taking part.
9 sites in 3 countries
India5 sites, 1 recruiting
- Completed
All India Institute of Medical Sciences-Delhi
Delhi, 110029
- Completed
Nirmal Hospital Pvt. Ltd.
Gujarat, 395002
- Completed
Suretech Hospital and Research Centre Ltd.
Maharashtra, 440012
- Not yet recruiting
Indira Gandhi Government Medical College & Hospital
Nagpur, 440018
- Completed
All India Institute of Medical Sciences (AIIMS), Raipur
Raipur, Chhattisgarh, 492099
Nigeria3 sites, 3 recruiting
- Recruiting
University College Hospital (UCH)
Ibadan, Oyo State, 200285
- Recruiting
Lagos University Teaching Hospital, Lagos
Lagos, 102215
- Recruiting
Aminu Kano Teaching Hospital (AKTH)
Tarauni, 700101
Oman1 site, 1 recruiting
- Recruiting
Sultan Qaboos University Hospital
Muscat, Sultanet of Oman/Muscat/Al Khoud, 123
About this study
The study will test a new medicine, etavopivat, for sickle cell disease and see if it is safe and help-ful for participants with sickle cell disease who are at an increased risk of stroke. Participants will be divided into two cohorts depending on their transcranial doppler (TCD) ultrasound results and whether or not they receive hydroxyurea (medication that they may already be taking). In one cohort, participants with conditional transcranial doppler (TCD) or participants with abnormal TCD who are not able to receive hydroxyurea will be included. The study doctor will determine if the TCD result is conditional or abnormal. In another cohort, participants with conditional TCD or participants with abnormal TCD who are receiving a stable dose of hydroxyurea will be included. The study doctor will determine if the TCD result is conditional or abnormal. The participant will start a 52-week (1 year) treatment period. The participant will take 400 milligrams (mg) of etavopivat once a day for the 52 weeks. The dose of 400 mg will be taken as 2 tablets by mouth, each containing 200 mg of etavopivat. Etavopivat may be taken with or without food. Each dose should be taken with a glass of water. As part of the study, the participants will be asked to visit the clinic frequently. The participant will have the opportunity to participate in a 48-week optional extension treatment period. The optional extension treatment period will allow continued as-sessment of safety of etavopivat in paediatric patients. At the end of the study, if deemed appro-priate the participant, the caregiver, and the study doctor, the participant may be offered the op-portunity to participate in a separate study to continue receiving etavopivat. If/when this separate study becomes available, the participant may only transfer to the new study after completion of the 52-week primary treatment period and at any time during the 48-week optional extension treatment period.
- Conditions
- Sickle Cell Disease
- Being tested
- Etavopivat, Hydroxyurea
- 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.
EtavopivatDrug
Participants will receive a dose of 400 mg (two 200 mg oral tablets) etavopivat once daily.
HydroxyureaDrug
Participants will receive a stable dose of HU.
| Study group | Role | What they receive |
|---|---|---|
| Etavopivat | Experimental | Participants will receive Etavopivat 400 mg once daily (QD) orally. Receives: Drug: Etavopivat |
| Etavopivat with HU | Experimental | Participants will receive Etavopivat 400 mg QD orally in combination with HU. The dose of HU (mg/kg) will be stable (no more than a 20% change in dosing except for weight-based changes) during the study, in the opinion of the Investigator. Receives: Drug: Etavopivat; Drug: Hydroxyurea |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in the highest TAMMV in any of the L/R internal carotid artery [ICA] and L/R middle cerebral artery [MCA], whichever is highest, as measured by TCD
Measured: Baseline and Week 12
Secondary outcomes (2)
Change in the highest TAMMV in any of the L/R internal carotid artery [ICA] and L/R middle cerebral artery [MCA], whichever is highest, as measured by TCD
Measured: Baseline, Weeks 2,4, 24 and 52
Incidence of conversion to normal (< 170 cm/s), conditionally abnormal (170-199 cm/s), and abnormal (≥ 200 cm/s) TCD velocities
Measured: Weeks 2, 4, 12, 24, and 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jul 2023
- Study start20 Jun 2023
- Primary completion20 Aug 2027 (estimated)
- Study completion28 Jun 2028 (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.
- 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 27 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Forma Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Transparency (dept. 2834), Study director, Novo Nordisk A/S
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05953584
- Sponsor's protocol ID
- 4202-HEM-204
- Other IDs
- PACTR202301655446404
- Acronym
- HIBISCUS 3
- Status last verified
- Sep 2026
- First submitted
- 11 Jul 2023
- Last updated
- 10 Sep 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com
Study at a glance
From the registry record, last updated by the sponsor on 10 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Open-label Study to Evaluate the Activity of Etavopivat on Transcranial Doppler Velocities in Pediatric Patients With Sickle Cell Disease Who Are at Increased Risk for Primary Stroke
- ClinicalTrials.gov ID
- NCT05953584
- Acronym / sponsor ID
- HIBISCUS 3 / 4202-HEM-204
- Conditions
- Sickle Cell Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 27 participants (estimated)
- Lead sponsor
- Forma Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 20 Jun 2023 (actual)
- Primary completion
- 20 Aug 2027 (estimated)
- Study completion
- 28 Jun 2028 (estimated)
- First posted
- 20 Jul 2023 (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 study will test a new medicine, etavopivat, for sickle cell disease and see if it is safe and help-ful for participants with sickle cell disease who are at an increased risk of stroke. Participants will be divided into two cohorts depending on their transcranial doppler (TCD) ultrasound results and whether or not they receive hydroxyurea (medication that they may already be taking). In one cohort, participants with conditional transcranial doppler (TCD) or participants with abnormal TCD who are not able to receive hydroxyurea will be included. The study doctor will determine if the TCD result is conditional or abnormal. In another cohort, participants with conditional TCD or participants with abnormal TCD who are receiving a stable dose of hydroxyurea will be included. The study doctor will determine if the TCD result is conditional or abnormal. The participant will start a 52-week (1 year) treatment period. The participant will take 400 milligrams (mg) of etavopivat once a day for the 52 weeks. The dose of 400 mg will be taken as 2 tablets by mouth, each containing 200 mg of etavopivat. Etavopivat may be taken with or without food. Each dose should be taken with a glass of water. As part of the study, the participants will be asked to visit the clinic frequently. The participant will have the opportunity to participate in a 48-week optional extension treatment period. The optional extension treatment period will allow continued as-sessment of safety of etavopivat in paediatric patients. At the end of the study, if deemed appro-priate the participant, the caregiver, and the study doctor, the participant may be offered the op-portunity to participate in a separate study to continue receiving etavopivat. If/when this separate study becomes available, the participant may only transfer to the new study after completion of the 52-week primary treatment period and at any time during the 48-week optional extension treatment period.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Etavopivat | Experimental | Drug: EtavopivatParticipants will receive Etavopivat 400 mg once daily (QD) orally. |
| Etavopivat with HU | Experimental | Drug: Etavopivat, Drug: HydroxyureaParticipants will receive Etavopivat 400 mg QD orally in combination with HU. The dose of HU (mg/kg) will be stable (no more than a 20% change in dosing except for weight-based changes) during the study, in the opinion of the Investigator. |
Who may qualify
- Ages
- 12 to 16 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (11 listed)
- Patient's parent, legal guardian, or legal representative has provided documented informed consent and patients have provided age-appropriate assent
- 12 to 16 years of age (inclusive) at time of screening
- Confirmed diagnosis of SCD
- TAMMV greater than or equal to (≥) 170 cm/s in the ICA and/or MCA during the Screening Period and confirmed on 2 occasions and without history of primary ischemic or hemorrhagic stroke, transient ischemic attack, or severe central nervous system (CNS) vasculopathy on magnetic resonance angiography (MRA). This includes patients with cTCD (170-199 centimeter per second [cm/s]) or aTCD (≥ 200 cm/s). Patients with aTCD cohort must have refused transfusion therapy.
- Hb ≥ 6 grams per deciliter (g/dL) and lesser than or equal to (≤) 9 g/dL at screening
Key exclusion criteria (13 listed)
- Medical Conditions
- Female who is breast feeding or pregnant
- History of seizure disorder
- Prior overt stroke (a focal neurological deficit of acute onset) by history or significant concerns for history of overt stroke based on Screening MRL, history of transient ischemic attack, focal neurological deficit on standardized neurological examination, or concern for moderate or severe neurological deficit (which could be due to stroke) based on a positive "10 questions" screening. Patients with significant or suggestive severe CNS vasculopathy (ie, moya moya) of Grade 4 or higher based on MRA read locally.
- Significant cytopenias (absolute neutrophil count [ANC] < 1.5 × 10^3/microliter (µL), platelets < 150,000/µL, reticulocytes < 80,000/µL)
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 |
|---|---|---|
| EtavopivatParticipants will receive a dose of 400 mg (two 200 mg oral tablets) etavopivat once daily. | Drug | Etavopivat, Etavopivat with HU |
| HydroxyureaParticipants will receive a stable dose of HU. | Drug | Etavopivat with HU |
Primary outcome
Change in the highest TAMMV in any of the L/R internal carotid artery [ICA] and L/R middle cerebral artery [MCA], whichever is highest, as measured by TCD
Time frame: Baseline and Week 12
2 secondary outcomes
Change in the highest TAMMV in any of the L/R internal carotid artery [ICA] and L/R middle cerebral artery [MCA], whichever is highest, as measured by TCD
Time frame: Baseline, Weeks 2,4, 24 and 52
Incidence of conversion to normal (< 170 cm/s), conditionally abnormal (170-199 cm/s), and abnormal (≥ 200 cm/s) TCD velocities
Time frame: Weeks 2, 4, 12, 24, and 52
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 10 Sep 2026.
- Individual participant dataSharing planned: Yes. According to the Novo Nordisk disclosure commitment on novonordisk-trials.com
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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.
Clinical Transparency (dept. 2834) study director
Novo Nordisk A/S
9 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Etavopivat and Hydroxyurea in people with Sickle Cell Disease, run by Forma Therapeutics, Inc. at 9 sites in 3 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 11 inclusion and 13 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: looking for participants now, as of the sponsor's last update on 10 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in India, Nigeria, Oman. 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. 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?
Contact Novo Nordisk ((+1) 866-867-7178, clinicaltrials@novonordisk.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in the highest TAMMV in any of the L/R internal carotid artery [ICA] and L/R middle cerebral artery [MCA], whichever is highest, as measured by TCD (time frame: Baseline and 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 10 Sep 2026.