A Study to Evaluate the Pharmacokinetics and Safety of Etavopivat in Pediatric Patients With Sickle Cell Disease (HIBISCUS KIDS)

A Single Arm, Open Label, Phase 1/2 Study to Evaluate the Pharmacokinetics and Safety of Etavopivat in Pediatric Patients With Sickle Cell Disease

This study is being done to learn about etavopivat, a once a day medicine taken by mouth in adolescents with sickle cell disease. The main goals are to study safety and how long etavopivat stays in the bloodstream, while also studying if there are benefits from taking etavopivat. Eligible participants who enter the study will start a 96-week treatment period. At the end of the 96 weeks, participants will have an end of study visit that occurs 4 weeks later. The participants will receive etavopivat every day throughout the treatment period.

Study Overview

• Status: Recruiting
• Conditions: Sickle Cell Disease
• Intervention / Treatment: Drug: Etavopivat

• Study Type: Interventional
• Enrollment (Estimated): 95
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Novo Nordisk; Phone Number: (+1) 866-867-7178; Email: clinicaltrials@novonordisk.com

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • Withdrawn
      • The Hospital for Sick Children
• France
  • Paris, France, 75019
    • Not yet recruiting
    • APHP - Centre de Référence des Syndromes
  • Pierre-Bénite, France, 69310
    • Not yet recruiting
    • Hospices Civils de Lyon-Hopital Lyon Sud
  • Roeun, France, 76031
    • Not yet recruiting
    • Centre Hospitalier Universitaire de Rouen-Hopital Charles Nicolle
• Kenya
  • Kericho, Kenya, 20200
    • Not yet recruiting
    • KEMRI-Walter-Reed Kericho
  • Kisumu, Kenya, 40100
    • Not yet recruiting
    • Kombewa Clinical Research Centre
  • Kisumu, Kenya, 40101
    • Recruiting
    • Ahero Clinical Trials Unit
  • Siaya, Kenya, 40100
    • Not yet recruiting
    • Kenya Medical Research Institute-Centre for Respiratory Disease Research, Siaya Clinical Research Annexe
• Lebanon
  • Beirut, Lebanon, 1107 2020
    • Recruiting
    • American University of Beirut Medical Center
  • Tripoli, Lebanon, 113-6044
    • Recruiting
    • Hospital Nini
• Nigeria
  • Lagos, Nigeria, 102215
    • Recruiting
    • Lagos University Teaching Hospital, Lagos
  • Tarauni, Nigeria, 700101
    • Recruiting
    • Aminu Kano Teaching Hospital (AKTH)
  • Enugu State
    • Ituku-Ozalla, Enugu State, Nigeria, 400001
      • Recruiting
      • University of Nigeria Teaching Hospital (UNTH)
• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye), 06100
    • Withdrawn
    • Hacettepe University pediatric hematology
  • Seyhan, Turkey (Türkiye), 1130
    • Withdrawn
    • Acıbadem Adana Hastanesi
• United Kingdom
  • London, United Kingdom, SE1 7EH
    • Recruiting
    • Guys and St Thomas NHS Foundation Trust / Evelina Childrens Hospital
  • London, United Kingdom, SE5 9RS
    • Recruiting
    • King's College Hospital - Alex Mowat Research Hub
  • Manchester, United Kingdom, M13 9WL
    • Recruiting
    • Manchester Royal Infirmary_1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Type of Participant and Disease Characteristics

  1. Patient's parent, legal guardian, or legal representative has provided documented informed consent and patients have provided age-appropriate assent

  2. Age greater than or equal to (≥) 6 months and lesser than (<) 18 years of age at time of enrollment, according to the enrolling cohort:

     • Cohort 1: age 12 to < 18 years (adolescents)
     • Cohort 2: age 6 to < 12 years
     • Cohort 3: age 2 to < 6 years
     • Cohort 4: age 6 months to < 2 years

  3. Patient has confirmed diagnosis of SCD

     • Documentation of SCD genotype (HbSS, HbSβ0-thalassemia or other sickle cell syndrome variants) 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 (HPLC), or similar testing. Note that Hb electrophoresis is performed by the local laboratory at Screening.

  4. Hemoglobin ≥ 5.5 and lesser than or equal to (≤) 10.5 grams per deciliter (g/dL)

  5. Pediatric patients with severe SCD, as defined by at least 1 of the following:

     • 2-15 episodes of documented VOC within the 12 months prior to screening. Documentation must exist in the patient's medical record prior to screening. Events based solely on patient recall without supporting documentation should not be counted towards eligibility.
     • Hospitalization for any SCD-related complication in the last 12 months prior to starting study treatment
     • Proteinuria, defined as an albumin:creatinine ratio (ACR) > 100 mg/g on 2 measures (separated by ≥ 1 month) as an indicator of early renal disease
     • History of a conditional TCD in the last 12 months prior to starting study treatment, but not currently being treated with chronic transfusion therapy (applicable to participants > 2 years of age). Conditional TCD is defined as a TAMMV of 170-199 cm/s by TCD or 155-184 cm/s by imaging TCD (TCDi).
  6. For participants taking hydroxyurea (HU), the dose of HU (mg/kg) must be stable (no more than a 20% change in dosing) for at least 90 days prior to start of study treatment with no anticipated need for dose adjustments during the study, in the opinion of the Investigator

  7. Patients on crizanlizumab or L-glutamine treatment at the time of consent may be eligible if they:

     • Have been on a stable dose for ≥ 12 months at the time of consent (ie, no changes to the dose except for changes to weight or for safety reasons)
     • For patients on crizanlizumab, have been ≥ 80% compliant with the planned regimen during the 12 months prior to the time of consent
  8. Female patients of childbearing potential who 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 male patients who 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.

Exclusion Criteria:

• Medical Conditions

  1. Female who is breastfeeding or pregnant
  2. More than 15 VOCs within the 12 months prior to starting study treatment that required a hospital, emergency room (ER), or clinic visit
  3. Hospitalized for sickle cell crisis or other vaso-occlusive event occurring in the 14 days prior to starting study treatment

  4. Abnormal TCD in the 12 months prior to starting study treatment

     Prior/Concomitant Therapy

  5. Patients receiving regularly scheduled blood (RBC) transfusion therapy (also termed chronic, prophylactic, or preventive transfusion)
  6. Received any blood products within 30 days of starting study treatment
  7. Receiving or use of concomitant medications that are strong inducers of cytochrome P450 (CYP) 3A4/5 within 2 weeks of starting study treatment
  8. Use of voxelotor within 28 days prior to starting study treatment or anticipated need for this agent during the study
  9. Receipt of erythropoietin or other hematopoietic growth factor treatment within 28 days of starting study treatment or anticipated need for such agents during the study
  10. Receipt of prior cellular based therapy (eg, hematopoietic cell transplant, gene modification therapy)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Etavopivat; Participants will receive Etavopivat once daily (QD) orally.	Drug: Etavopivat; Participants will receive oral tablets of etavopivat once daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Single-dose: maximum plasma concentration (Cmax)	During the 24-week primary treatment period
Single-dose: area under the plasma concentration time curve from dosing (time 0) to time t ((AUC)0-t)	During the 24-week primary treatment period
Single-dose: area under the plasma concentration time curve from zero to time infinity (AUC0-inf)	During the 24-week primary treatment period
Steady-state maximum plasma concentration (Cmax,ss)	During the 24-week primary treatment period
Steady-state area under the concentration time curve over the dosing interval (AUCtau,ss)	During the 24-week primary treatment period
Steady-state average plasma concentration (Cavg,ss)	During the 24-week primary treatment period
Steady-state minimum plasma concentration (Cmin,ss)	During the 24-week primary treatment period
Incidence of adverse events (AEs), serious adverse events (SAEs), and AEs related to etavopivat	During the 24-week primary treatment period
Number of premature discontinuations	During the 24-week primary treatment period
Number of dose interruptions	During the 24-week primary treatment period
Number of dose reductions	During the 24-week primary treatment period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of AEs, SAEs, and AEs related to etavopivat		During the 72-week treatment extension period
Number of premature discontinuations		During the 72-week treatment extension period
Number of dose interruptions		During the 72-week treatment extension period
Number of dose reductions		During the 72-week treatment extension period
Hemoglobin (Hb) response rate		Baseline, week 12 and 24
Change in Hb from baseline		Baseline, week 12 and 24
Change from baseline in number of vaso-occlusive crises (VOCs)		Baseline and week 24
Change from baseline in Annualized Rate of VOC		Baseline and week 24
Change from baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue Scale	PROMIS is a 10-item patient-reported health outcome measurement system used to evaluate quality of life in both children and adults. The assessment is based on the responses - 1. Never, 2. Almost never, 3. Sometimes, 4. Often and 5. Almost always. 'Never' response on the PROMIS fatigue scale indicates better quality of life.	Baseline, week 12 and 24
Change from baseline in time-averaged mean of the maximum velocity (TAMMV) by transcranial Doppler ultrasonography (TCD)		Baseline, week 24, 48, and 96

Collaborators and Investigators

• Sponsor: Forma Therapeutics, Inc.
• Collaborators: Novo Nordisk A/S
• Investigators: Study Director: Clinical Transparency (dept. 2834), Novo Nordisk A/S

Study record dates

Study Major Dates

• Study Start (Actual): January 12, 2023
• Primary Completion (Estimated): February 23, 2028
• Study Completion (Estimated): August 8, 2029

Study Registration Dates

• First Submitted: December 27, 2023
• First Submitted That Met QC Criteria: December 27, 2023
• First Posted (Actual): January 10, 2024

Study Record Updates

• Last Update Posted (Actual): April 24, 2026
• Last Update Submitted That Met QC Criteria: April 23, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; Anemia, Sickle Cell
• Other Study ID Numbers: 4202-HEM-202; 2022-001689-36 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes