A Research Study Looking at Long-term Treatment With Etavopivat in People With Sickle Cell Disease or Thalassaemia (FLORAL)

An Open-label, Multi-centre, Rollover Study to Characterise Long-term Safety and Efficacy of Etavopivat in Adults, Adolescents and Children Who Have Sickle Cell Disease or Thalassaemia and Have Completed a Treatment Period in an Etavopivat Study

Etavopivat is a new medicine under development for treating blood disorders like sickle cell disease and thalassaemia. Sickle cell disease and thalassaemia are inherited blood disorders that affect haemoglobin. Haemoglobin is the protein that carries oxygen through the body. This study is looking into how safe treatment with etavopivat is and how well it works over a long period of time. The study will last for up to 264 weeks, but it will end earlier if etavopivat is approved in the participant's country.

Study Overview

• Status: Recruiting
• Conditions: Sickle Cell Disease; Thalassemia
• Intervention / Treatment: Drug: Etavopivat A; Drug: Etavopivat B; Drug: Etavopivat C

• Study Type: Interventional
• Enrollment (Estimated): 480
• Phase: Phase 3

Contacts and Locations

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

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z1Y6
      • Active, not recruiting
      • St Pauls Hospital
  • Ontario
    • Toronto, Ontario, Canada, M5G 2C4
      • Active, not recruiting
      • University Health Network - Toronto General Hospital
    • Toronto, Ontario, Canada, M5G 1X8
      • Active, not recruiting
      • The Hospital for Sick Children
  • Quebec
    • Montreal, Quebec, Canada, H3T 1C5
      • Active, not recruiting
      • CHU Ste-Justine
• Egypt
  • Alexandria, Egypt, Egypt, 21131
    • Not yet recruiting
    • Alexandria University Hospital
  • Alsharkia, Egypt, Egypt, 44519
    • Not yet recruiting
    • Zagazig university hospital
  • Cairo, Egypt, 1181
    • Not yet recruiting
    • Faculty of Medicine Ain Shams Medical Research Institute (MASRI)
  • Cairo, Egypt, Egypt, 11956
    • Recruiting
    • Cairo university
  • Cairo, Egypt, Egypt, 4241317
    • Recruiting
    • Abu El-Reesh El-Mounira Children University Hospital
• France
  • Créteil, France, 94000
    • Not yet recruiting
    • Ap-Hp-Hopital Henri Mondor
  • Lyon, France, 69437
    • Not yet recruiting
    • Hospices Civils de Lyon-Hopital Edouard Herriot
  • Paris, France, 75019
    • Recruiting
    • Ap-Hp-Hopital Robert Debre
  • Paris, France, 75019
    • Not yet recruiting
    • Ap-Hp-Hopital Robert Debre
• Germany
  • Berlin, Germany, 13353
    • Not yet recruiting
    • Charité - Campus Virchow-Klinikum - Klinik für Pädiatrie mit Schwerpunkt Onkologie und Hämatologie
  • Freiburg im Breisgau, Germany, 79106
    • Recruiting
    • Universitätsklinikum Freiburg - Kinder- und Jugendklinik
• Ghana
  • Accra, Ghana
    • Not yet recruiting
    • Ghana Institute of Clinical Genetics, Korle Bu Teaching Hospital (KBTH)
  • Bono East
    • Kintampo, Bono East, Ghana, 27WF+98M
      • Not yet recruiting
      • Kintampo Health Research Centre (KHRC)
• Greece
  • Athens, Greece, 11527
    • Recruiting
    • Hippokration Hospital
  • Pátrai, Greece, 26504
    • Recruiting
    • General University Hospital of Patras
  • Thessaloniki, Greece, 54642
    • Recruiting
    • 'Ippokrateio' General Hospital of Thessaloniki
  • Thessaly
    • Larissa, Thessaly, Greece, 41221
      • Recruiting
      • General Hospital Of Larissa Koutlibaneio And Triantafylleio - Thalassemia and SCD Unit
• India
  • Bangalore, India, 560002
    • Not yet recruiting
    • Victoria Hospital, Bangalore
  • Gujarat, India, 395002
    • Not yet recruiting
    • Nirmal Hospital Pvt. Ltd.
  • Maharashtra, India, 440012
    • Not yet recruiting
    • Suretech Hospital and Research Centre Ltd.
  • New Delhi, India, 110029
    • Not yet recruiting
    • All India Institute of Medical Sciences_Delhi
  • Chhattisgarh
    • Raipur, Chhattisgarh, India, 492099
      • Not yet recruiting
      • All India Institute of Medical Sciences (AIIMS), Raipur
  • Maharashtra
    • Mumbai, Maharashtra, India, 400022
      • Not yet recruiting
      • K.J Somaiya Hospital and Research Centre
• Italy
  • Padua, Italy, 35128
    • Recruiting
    • Azienda Ospedale Universita Padova
  • Pavia, Italy, 27100
    • Recruiting
    • Fondazione IRCCS Policlinico San Matteo
  • Torino
    • Orbassano, Torino, Italy, 10043
      • Recruiting
      • Azienda Ospedaliera Universitaria San Luigi Gonzaga - S.C.D.O. Microcitemie e malattie rare ematologiche
• Kenya
  • Kericho, Kenya, 20200
    • Not yet recruiting
    • KEMRI-Walter-Reed Kericho
  • Kisumu, Kenya, 40100
    • Recruiting
    • KEMRI Kondele Children Hospital, Kisumu
  • Kisumu, Kenya, 1932
    • Not yet recruiting
    • Kombewa Clinical Research Centre
  • Kisumu, Kenya, 40101
    • Recruiting
    • Ahero Clinical Trials Unit
  • Nairobi County
    • Nairobi, Nairobi County, Kenya, 00509
      • Not yet recruiting
      • Gertrude's Children's Hospital
  • Siaya County
    • Siaya, Siaya County, Kenya, 40600
      • Not yet recruiting
      • KEMRI CRDR Siaya Clinical Research Annex, Country Referral Hospital
• Lebanon
  • Hamra, Lebanon, 11-0236
    • Recruiting
    • American University of Beirut Medical Centre
  • Hazmiyeh, Lebanon, 21211
    • Recruiting
    • Chronic Care Center
  • Tripoli, Lebanon, 1434
    • Recruiting
    • Hospital Nini
• Nigeria
  • Abuja, Nigeria, 228
    • Not yet recruiting
    • University of Abuja Teaching Hospital, Gwagwalada, Abuja
  • Kaduna, Nigeria, 800212
    • Not yet recruiting
    • Barau Dikko Teaching Hospital, Kaduna
  • Kano, Nigeria, 3452
    • Not yet recruiting
    • Aminu Kano Teaching Hospital (AKTH)
  • Lagos, Nigeria, 102215
    • Not yet recruiting
    • Lagos University Teaching Hospital, Lagos
  • Enugu State
    • Ituku-Ozalla, Enugu State, Nigeria, 400001
      • Not yet recruiting
      • University of Nigeria Teaching Hospital (UNTH)
  • Oyo State
    • Ibadan, Oyo State, Nigeria, 0000
      • Not yet recruiting
      • University College Hospital Paediatric Haematology and Oncology Unit, Ibadan
• Oman
  • Sultanet of Oman/Muscat/Al Khoud
    • Muscat, Sultanet of Oman/Muscat/Al Khoud, Oman, 123
      • Recruiting
      • Sultan Qaboos University Hospital
• Saudi Arabia
  • Jizan, Saudi Arabia, 82943
    • Not yet recruiting
    • Prince Mohammad Bin Naser Hospital
  • Riyadh, Saudi Arabia, 12372
    • Recruiting
    • King Khalid University Hospital
• Spain
  • Barakaldo, Spain, 48903
    • Active, not recruiting
    • Hospital Universitario de Cruces
  • Barcelona, Spain, 08035
    • Recruiting
    • Hospital Vall d'Hebron
  • Madrid, Spain, 28046
    • Recruiting
    • Hospital Universitario La Paz
• Turkey (Türkiye)
  • Adana, Turkey (Türkiye), 01250
    • Not yet recruiting
    • Baskent Universitesi Adana
  • Adana, Turkey (Türkiye), 01250
    • Recruiting
    • Başkent Üniversitesi Adana-Hematoloji
  • Ankara, Turkey (Türkiye), 06230
    • Not yet recruiting
    • Hacettepe University Hematology
  • Ankara, Turkey (Türkiye), 06230
    • Not yet recruiting
    • Hacettepe Üniversitesi Hastanesi- Hematoloji
  • Mersin, Turkey (Türkiye), 33110
    • Not yet recruiting
    • Mersin University Medical Faculty Pediatric Hematology
  • Mersin, Turkey (Türkiye), 33110
    • Recruiting
    • Mersin Üniversitesi Tip Fakültesi Hastanesi- Çiftlikköy Yerleşkesi- Hematoloji
• United Kingdom
  • London, United Kingdom, SE1 9RT
    • Not yet recruiting
    • Guy's Hospital
  • London, United Kingdom, W12 0NN
    • Recruiting
    • Imperial College London
  • London, United Kingdom, SE5 9RS
    • Recruiting
    • Kings College Hospital - Haematology
  • London, United Kingdom, SE5 9RS
    • Recruiting
    • King's College Hospital - Paediatric Research
  • London, United Kingdom, SE1 9RT
    • Recruiting
    • Guy's Hospital - Haematology
  • Manchester, United Kingdom, M13 9WL
    • Recruiting
    • Manchester Royal Infirmary
  • Sheffield, United Kingdom, S10 2JF
    • Recruiting
    • Royal Hallamshire Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Active, not recruiting
      • Univ of Alabama Birmingham
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Recruiting
      • Phoenix Children's Hsptl
  • California
    • Los Angeles, California, United States, 90027
      • Active, not recruiting
      • Children's Hospital Los Angeles - Endocrinology
    • Los Angeles, California, United States, 90027
      • Recruiting
      • Children's Hospital Los Angeles - Endocrinology
    • Oakland, California, United States, 94609
      • Recruiting
      • UCSF Oakland Benioff ChildHosp
    • Oakland, California, United States, 94609
      • Active, not recruiting
      • UCSF Oakland Benioff ChildHosp
    • Orange, California, United States, 92868
      • Recruiting
      • University of California Irvine
    • Orange, California, United States, 92868
      • Completed
      • Children's Hosp Of Orange
  • Connecticut
    • Farmington, Connecticut, United States, 06030
      • Active, not recruiting
      • University of Connecticut
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20010
      • Completed
      • Children's National Medical Center
  • Florida
    • Hollywood, Florida, United States, 33023
      • Recruiting
      • Foundation for Sickle Cell Disease Research
    • Miami, Florida, United States, 33136
      • Completed
      • Univ of Miami/SCCC
  • Georgia
    • Atlanta, Georgia, United States, 30329
      • Recruiting
      • Children's Healthcare Atlanta
    • Atlanta, Georgia, United States, 30303
      • Active, not recruiting
      • Emory University School of Medicine
    • Augusta, Georgia, United States, 30912
      • Recruiting
      • Center for Blood Disorders Augusta University
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Not yet recruiting
      • Univer Of Illinois at Chicago
  • Louisiana
    • New Orleans, Louisiana, United States, 70118
      • Completed
      • Children's Hosp-New Orleans
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Active, not recruiting
      • Boston Medical Center
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University-St.Louis
  • New York
    • Brooklyn, New York, United States, 11203
      • Recruiting
      • NYC Health+Hospitals
    • New York, New York, United States, 10065
      • Recruiting
      • Weill Cornell Med Coll-NYPH
    • New York, New York, United States, 10032
      • Not yet recruiting
      • Columbia University Medical Center_New York_0
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Medical Center_New York_0
    • The Bronx, New York, United States, 10467
      • Not yet recruiting
      • Montefiore Medical Center
    • The Bronx, New York, United States, 10461
      • Active, not recruiting
      • Jacobi Medical Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Not yet recruiting
      • Atrium Levine Children's/Atrium Health
    • Durham, North Carolina, United States, 27705
      • Recruiting
      • Duke University_Durham
    • Greenville, North Carolina, United States, 27834
      • Active, not recruiting
      • East Carolina Univ-Greenville
    • Greenville, North Carolina, United States, 27834
      • Completed
      • East Carolina University_Greenville
    • Winston-Salem, North Carolina, United States, 27157
      • Recruiting
      • Atrium Health-Wake Forest Bapt
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Active, not recruiting
      • Cincinnati Child's Hsp Med Ctr
    • North Canton, Ohio, United States, 44720
      • Active, not recruiting
      • Neuro-Behavioral Clinical Research
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Recruiting
      • Medical University Of South Carolina_Charleston
  • Tennessee
    • Memphis, Tennessee, United States, 38104
      • Recruiting
      • Methodist University Hospital
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • UT Health University of Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • Texas Children's Hospital_Houston
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Recruiting
      • Virginia Comm Univ Medical Ctr
  • Washington
    • Tacoma, Washington, United States, 98405
      • Active, not recruiting
      • Mary Bridge Children's Health
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Not yet recruiting
      • Versiti, CCBD_Milwaukee

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Participant must have ongoing participation in an etavopivat parent study for treatment of sickle cell disease (SCD) or thalassaemia and have completed at least a treatment period of the parent study.
• Participant must have derived clinical benefit from treatment with etavopivat, as determined by the investigator.
• Any participant with dose reduction or temporary discontinuation will need to be successfully rechallenged to the full dose of etavopivat before transferring.
• Participants on hydroxyurea (HU), crizanlizumab or l-glutamine oral powder (Endari®) treatment at the time of consent may be eligible if they have been on a stable dose in the parent study as defined at the investigator's discretion. Necessary adjustments related to weight or age are accepted. Participants with temporary dose reductions or pauses due to medical reasons may still be considered to have a stable dose, as determined by the investigator, who will assess the impact of these adjustments based on clinical context and the participant's overall health status.

Exclusion Criteria:

• Any disorder, except for conditions associated with SCD or thalassaemia, which in the investigator's opinion might jeopardise participant's safety or compliance with the protocol.
• Participant withdrew or had permanent treatment discontinuation from an etavopivat clinical study.
• Participants on permanent dose reduction (greater than [>] 28 days or more) or ongoing temporary treatment discontinuation.
• Use of any of the following within the timeframes prior to the transfer visit as stated:
• Use of haemoglobin S (HbS) polymerisation inhibitors within participation of the parent study or anticipated need for this agent during this study.
• Use of an experimental selectin antagonist (e.g., monoclonal antibody or small molecule) within the parent study or anticipated need for such agents during this study.
• Use of erythropoietin or other haematopoietic growth factor treatment for more than 4 consecutive weeks during the parent study or anticipated need of such agents for a maintenance treatment during this study.
• Receiving or use of concomitant medications that are strong inducers of cytochrome P450 (CYP) 3A4 within 2 weeks of the transfer visit or anticipated need for such agents during the study.
• Current participation in a study that is not a designated parent study, or planned participation in any other clinical study, for the duration of FLORAL.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Participants greater than or equal to (≥) 12 years old with sickle cell disease; Participants will receive an oral dose of Etavopivat A or C.	Drug: Etavopivat A; Participants will receive an oral dose of Etavopivat A.; Drug: Etavopivat C; Participants will receive an oral dose of Etavopivat C.
Experimental: Participants ≥ 12 years old with sickle cell disease transfusion dependent; Participants will receive an oral dose of Etavopivat A or C.	Drug: Etavopivat A; Participants will receive an oral dose of Etavopivat A.; Drug: Etavopivat C; Participants will receive an oral dose of Etavopivat C.
Experimental: Participants ≥ 12 years old with transfusion-dependent thalassaemia; Participants will receive an oral dose of Etavopivat A or C.	Drug: Etavopivat A; Participants will receive an oral dose of Etavopivat A.; Drug: Etavopivat C; Participants will receive an oral dose of Etavopivat C.
Experimental: Participants ≥ 12 years old with non-transfusion dependent thalassaemia; Participants will receive an oral dose of Etavopivat A or C.	Drug: Etavopivat A; Participants will receive an oral dose of Etavopivat A.; Drug: Etavopivat C; Participants will receive an oral dose of Etavopivat C.
Experimental: Participants ≥ 2 years to less than (<) 12 years old with sickle cell disease; Participants ≥ 12 years of age will receive an oral dose of Etavopivat A or C and participants < 12 years of age will receive an oral dose of Etavopivat B.	Drug: Etavopivat A; Participants will receive an oral dose of Etavopivat A.; Drug: Etavopivat B; Participants will receive an oral dose of Etavopivat B.; Drug: Etavopivat C; Participants will receive an oral dose of Etavopivat C.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of treatment emergent adverse events (TEAEs), reported for each indication and age group separately	Measured as number of events.	Baseline (week 0 of FLORAL) up to end of study (up to week 316)
Number of adverse reactions, reported for each indication and age group separately	Measured as number of adverse reactions.	Baseline (week 0 of FLORAL) up to end of study (up to week 316)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Annualised vaso-occlusive crisis (VOC) rates, reported for each age group separately	Measured as count.	Baseline (week 0 of FLORAL) up to end of treatment (up to week 312)
Change in VOCs, reported for each age group separately	Measured as count.	Baseline (of parent study [i.e., the previous etavopivat study that a participant is rolling over from]) up to end of treatment (up to week 312)
Change in hemoglobin (Hb) concentration, reported for each age group separately	Measured as grams per deciliter (g/dL).	Baseline (of parent study [i.e., the previous etavopivat study that a participant is rolling over from]) up to end of treatment (up to week 312)
Annualised number of hospitalisations, reported for each age group separately	Measured as count.	Baseline (week 0 of FLORAL) up to end of treatment (up to week 312)
Average length of stay of hospitalisations, reported for each age group separately	Measured as days.	Baseline (week 0 of FLORAL) up to end of treatment (up to week 312)
Change in Hb concentration	Measured as g/dL.	Baseline (of parent study [i.e., the previous etavopivat study that a participant is rolling over from]) up to end of treatment (up to week 312)
Number of red blood cell (RBC) units transfused, reported for each indication separately	Measured as units.	Baseline (week 0 of FLORAL) up to end of treatment (up to week 312)
Change in RBC units transfused, reported for each indication separately	Measured as units.	Baseline (of parent study [i.e., the previous etavopivat study that a participant is rolling over from]) up to end of treatment (up to week 312)

Collaborators and Investigators

• Sponsor: 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 10, 2025
• Primary Completion (Estimated): December 30, 2030
• Study Completion (Estimated): December 30, 2030

Study Registration Dates

• First Submitted: September 20, 2024
• First Submitted That Met QC Criteria: September 20, 2024
• First Posted (Actual): September 24, 2024

Study Record Updates

• Last Update Posted (Actual): March 24, 2026
• Last Update Submitted That Met QC Criteria: March 23, 2026
• Last Verified: March 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; Thalassemia
• Other Study ID Numbers: NN7535-7822; U1111-1301-8130 (Other Identifier: Universal Trial Number); 2024-510805-27 (Other Identifier: EU CT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No