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Active, not recruitingNCT04624659HIBISCUSUpdated Apr 6, 2026

A Study of Etavopivat in Adults and Adolescents With Sickle Cell Disease (HIBISCUS)

A Phase 3 interventional study of Etavopivat Tablets Low dose and Etavopivat Tablets High dose in Sickle Cell Disease, sponsored by Forma Therapeutics, Inc.. Active, not recruiting at 142 sites in 17 countries. Open to participants aged 12 Years to 65 Years. Per ClinicalTrials.gov, last updated 2026-04-06.

Sponsored by Forma Therapeutics, Inc. (part of Novo Nordisk A/S) · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
450
Allocation
Randomized
Ages
12 Years to 65 Years
Sex
All
01

Study summary

This clinical trial is a Phase 2/3 study that will evaluate the efficacy and safety of etavopivat and test how well etavopivat works compared to placebo to improve the amount of hemoglobin in the blood and to reduce the number of vaso-occlusive crises (times when the blood vessels become blocked and cause pain).

Read the detailed description

Etavopivat is designed to activate PKR and thereby modulate RBC metabolism by impacting two critical pathways in RBCs. The etavopivat clinical development program will investigate whether decreasing 2,3-DPG may help oxygen bind to hemoglobin (i.e. increasing oxygen affinity), and thereby increase ATP and impact RBC function. This study is a randomized, placebo-controlled, double-blind, multicenter Phase 2/3 study of patients age 12 to 65 years (inclusive), with sickle cell disease. There is one planned interim analyses in this study design. Initially, patients will be randomized at 1:1:1 to one of two dose levels of etavopivat or placebo. At the first interim analysis, one of the two etavopivat dose levels will be selected for the Phase 3 portion of the study, in which patients will be randomized at 1:1 to the selected etavopivat dose or placebo. Efficacy on hemoglobin will be evaluated at conclusion of the double-blind treatment period. Following completion of 52 weeks of double-blind treatment, patients may enter a 112-week etavopivat open-label extension period.

02

Conditions studied

  • Sickle Cell Disease

Keywords

  • Sickle Cell Disease
  • Sickle Cell
  • Anemia
  • Sickle Cell Anemia
  • Hemolytic
  • Hemoglobin
  • Vaso-occlusive Crisis
  • Sickle Cell Crisis
  • Congenital Anemia
  • Hemolytic Anemia
  • Hematologic Disease
  • Hemoglobinopathies
  • Genetic Disease
  • Inborn Disease
  • Sickle Cell Trait
  • Pyruvate Kinase
03

In context

Anemia, Sickle Cell

1,134 studies on the registry are indexed under Anemia, Sickle Cell; 238 are open to participants now.

This study's planned enrollment of 450 is above the median of 40 across 769 interventional studies indexed under Anemia, Sickle Cell.

Browse Anemia, Sickle Cell studies →

Lead sponsor

Forma Therapeutics, Inc. is the lead sponsor of 10 studies on the registry; 2 are open to participants now.

Of its 5 completed or terminated interventional studies of FDA-regulated products, 3 (60%) have results posted.

First submitted before Forma Therapeutics, Inc. became part of Novo Nordisk A/S.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
12 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

Key Inclusion Criteria:

  • Provision of consent
  • Patient has a confirmed diagnosis of sickle cell disease
  • At least 2 episodes of vaso-occlusive crises in the past 12 months
  • ≥ 5.5 and ≤ 10.5 g/dL (≥ 55 and ≤ 105 g/L) during screening
  • Patients taking hydroxyurea, must demonstrate a stable dose for at least 90 days prior to start of study treatment
  • Patients on crizanlizumab or L-glutamine treatment at the time of consent must be on a stable dose for ≥ 12 months and must be ≥ 80% compliant with the planned regimen at the time of consent and meet the VOC eligibility criteria
  • Female patients of must use highly effective methods of , male patients are willing to use barrier methods of contraception

Key Exclusion Criteria:

  • More than 15 vaso-occlusive crises within the past 12 months
  • Female who is breastfeeding or pregnant
  • Hepatic dysfunction characterized by:

    • (ALT) > 4.0 × (ULN)
    • Direct > 3.0 × ULN
  • Known positivity
  • Active or infection
  • Severe renal dysfunction or on chronic dialysis
  • History of unstable or deteriorating cardiac or pulmonary disease within 6 months prior to consent including but not limited to the following:

    • Unstable angina pectoris or myocardial infarction or elective coronary intervention
    • Congestive heart failure requiring hospitalization
    • Uncontrolled arrhythmias
    • Symptomatic pulmonary hypertension
  • History of overt clinical stroke within previous 2 years or any history of an intracranial hemorrhage
  • History of deep venous thrombosis requiring systemic anti-coagulation therapy for ≥ 6 weeks, occurring within 6 months prior to Day 1 of study treatment.

Prior/Concomitant Therapy

  • Patients receiving regularly scheduled blood (RBC) transfusion therapy (also termed chronic, prophylactic, or preventive transfusion)
  • Receiving or use of concomitant medications that are strong inducers of /5 within 2 weeks of starting study treatment or anticipated need for such agents during the study
  • Use of voxelotor within 28 days prior to starting study treatment or anticipated need for this agent during the study
  • Use of an experimental selectin antagonist (eg, monoclonal antibody or small molecule) within 28 days of starting study treatment or anticipated need for such agents during the study
  • Use of erythropoietin or other hematopoietic growth factor treatment within 28 days of starting study treatment or anticipated need for such agents during the study
  • Receipt of prior cellular-based therapy (eg, hematopoietic cell transplant, gene modification therapy)
Terms in these criteria, in plain language(11)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Hemoglobin (Hb)

The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).

Childbearing potential

Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).

Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.

Contraception

Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.

Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.

ALT and AST (liver enzymes)

Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.

Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.

ULN (upper limit of normal)

The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.

“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.

Bilirubin

A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.

Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.

HIV

The human immunodeficiency virus, which weakens the immune system.

Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.

Hepatitis B tests

Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.

Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.

Hepatitis C tests

Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.

After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.

Clinically significant

Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.

CYP3A (CYP3A4) inhibitors and inducers

CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.

Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.

05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
450 participants (estimated)

Study arms

  • Experimental
    Double blind etavopivat Low Dose

    Double blind etavopivat Low Dose

    Drug: Etavopivat Tablets Low dose

  • Experimental
    Double blind etavopivat High Dose

    Double blind etavopivat High Dose

    Drug: Etavopivat Tablets High dose

  • Experimental
    Double blind placebo

    Double blind placebo

    Drug: Placebo Tablets

  • Experimental
    Open label etavopivat

    Open label etavopivat

    Drug: Etavopivat Tablets

Interventions

06

What researchers measure

Primary outcomes

  1. Hemoglobin response rate

    Hemoglobin response rate at Week 24 (increase of \> 1 g/dL \[\> 10 g/L\] from baseline) during the blinded treatment period

    Time frame: 24 Weeks

  2. Annualized vaso-occlusive crisis

    Annualized vaso-occlusive crisis rate during the 52-week blinded treatment period based on adjudicated vaso-occlusive crisis review

    Time frame: 52 Weeks

Secondary outcomes

  1. Hemoglobin

    Change from baseline in hemoglobin at Week 52 during the blinded treatment period

    Time frame: 52 Weeks

  2. Absolute reticulocyte count

    Change in absolute reticulocyte count from baseline at Week 24 during the blinded treatment period

    Time frame: 24 Weeks

  3. Indirect bilirubin

    Change in unconjugated bilirubin from baseline at Week 24 during the blinded treatment period

    Time frame: 24 Weeks

  4. Lactate dehydrogenase

    Change in lactate dehydrogenase from baseline at Week 24 during the blinded treatment period

    Time frame: 24 Weeks

  5. Vaso-occlusive crisis

    Time to first vaso-occlusive crisis during the blinded treatment period

    Time frame: 52 Weeks

  6. Fatigue

    Change in Patient-Reported Outcome Measurement Information System (PROMIS) Fatigue Scale from baseline in adult patients at Week 52 during the blinded treatment period

    Time frame: 52 Weeks

07

Study locations

142 sites

Showing the first 100 of 142 sites across 17 countries. Choose a country and city above to see the rest.

08

References and documents

Publications

  • Obadina M, Wilson S, Derebail VK, Little J. Emerging Therapies and Advances in Sickle Cell Disease with a Focus on Renal Manifestations. Kidney360. 2023 Jul 1;4(7):997-1005. doi: 10.34067/KID.0000000000000162. Epub 2023 May 31. PubMed 37254256 ↗
  • Forsyth S, Schroeder P, Geib J, Vrishabhendra L, Konstantinidis DG, LaSalvia K, Ribadeneira MD, Wu E, Kelly P, Kalfa TA. Safety, Pharmacokinetics, and Pharmacodynamics of Etavopivat (FT-4202), an Allosteric Activator of Pyruvate Kinase-R, in Healthy Adults: A Randomized, Placebo-Controlled, Double-Blind, First-in-Human Phase 1 Trial. Clin Pharmacol Drug Dev. 2022 May;11(5):654-665. doi: 10.1002/cpdd.1058. Epub 2022 Jan 12. PubMed 35019238 ↗
09

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reachedSimilar studies: half by the dot; the band is the middle halfHalf of similar studies reached it by the dot; the band is the middle half, from a quarter to three quarters

Ran from Jan 2021 to primary completion in Feb 2026, 60 months.

Of 35 phase 3 interventional studies under Anemia, Sickle Cell, half reached primary completion within 48 months of starting (the median), counting those still running; a quarter within 36 and three quarters within 61. This study's 60 months is above that.

How these figures are worked out, and which studies are left out of them.

Registered
Nov 5, 2020
First posted
Nov 12, 2020
StartActual
Jan 29, 2021
Primary completionActual
Feb 6, 2026
CompletionEst.
Mar 19, 2027
Last update
Apr 6, 2026
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Apr 6, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT04624659
Collaborators
This study is currently undergoing a sponsor transition from Forma to Novo Nordisk. Sponsor field will be updated once the transition is complete.
Responsible party
Sponsor
First posted
Nov 12, 2020
Start date
Jan 29, 2021
Primary completion
Feb 6, 2026
Completion
Mar 19, 2027 (estimated)
Last update
Apr 6, 2026

Study contacts

Clinical Transparency (dept. 2834)
study director · Novo Nordisk A/S

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is active, not recruiting, as verified in Mar 2026. You cannot join it, but the record below documents what was studied.

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Studies of the drug tested here: Etavopivat

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