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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06612268




Registration number
NCT06612268
Ethics application status
Date submitted
23/09/2024
Date registered
25/09/2024

Titles & IDs
Public title
A Research Study to Evaluate How Well Etavopivat Works in People With Sickle Cell Disease
Scientific title
A Global Phase 3, Randomised, Double-blind and Placebo-controlled Study Evaluating the Efficacy and Safety of Etavopivat in Adolescents and Adults With Sickle Cell Disease
Secondary ID [1] 0 0
U1111-1298-3431
Secondary ID [2] 0 0
NN7535-7807
Universal Trial Number (UTN)
Trial acronym
Hibiscus 2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Sickle Cell Disease 0 0
Condition category
Condition code
Blood 0 0 0 0
Anaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Etavopivat
Treatment: Drugs - Placebo

Experimental: Etavopivat - Participants will be randomised to receive oral dose of Etavopivat.

Placebo comparator: Placebo - Participants will be randomised to receive oral dose of placebo.


Treatment: Drugs: Etavopivat
Etavopivat will be administered orally.

Treatment: Drugs: Placebo
Placebo matching Etavopivat will be administered orally.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of adjudicated Vaso-occlusive crisis (VOC) events with a medical contact
Timepoint [1] 0 0
Baseline (week 0) to week 52
Primary outcome [2] 0 0
Time to onset of first adjudicated Vaso-occlusive crisis (VOC)
Timepoint [2] 0 0
Baseline (week 0) to week 52
Primary outcome [3] 0 0
Change in distance travelled during the 6-minute walking test (6MWT)
Timepoint [3] 0 0
Baseline (week 0) to week 52
Primary outcome [4] 0 0
Change in standardised T-score on the Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue 7a Scale
Timepoint [4] 0 0
Baseline (week 0) to week 52
Secondary outcome [1] 0 0
Change in haemoglobin (Hb)
Timepoint [1] 0 0
Baseline (week 0) to week 52
Secondary outcome [2] 0 0
Change in Haemoglobin (Hb) greater than 1 grams per decilitre (g/dL)
Timepoint [2] 0 0
Baseline (week 0) to week 52
Secondary outcome [3] 0 0
Change in lactate dehydrogenase (LDH)
Timepoint [3] 0 0
Baseline (week 0) to week 52
Secondary outcome [4] 0 0
Change in absolute reticulocyte count
Timepoint [4] 0 0
Baseline (week 0) to week 52
Secondary outcome [5] 0 0
Change in indirect bilirubin
Timepoint [5] 0 0
Baseline (week 0) to week 52
Secondary outcome [6] 0 0
Changes in estimated glomerular filtration rate (eGFR)
Timepoint [6] 0 0
Baseline (week 0) to week 52
Secondary outcome [7] 0 0
Change in albumin:creatinine ratio (ACR)
Timepoint [7] 0 0
Baseline (week 0) to week 52
Secondary outcome [8] 0 0
Occurrence of moderate/severe albuminuria (yes/no)
Timepoint [8] 0 0
Baseline (week 0) to week 52
Secondary outcome [9] 0 0
Change in N-terminal pro b-type natriuretic peptide (NT-pro-BNP)
Timepoint [9] 0 0
Baseline (week 0) to week 52
Secondary outcome [10] 0 0
Proportion of participants achieving the threshold for clinically meaningful change (yes/no) in PROMIS fatigue scale 7a
Timepoint [10] 0 0
Baseline (week 0) to week 52
Secondary outcome [11] 0 0
Proportion of participants achieving the threshold for clinically meaningful change (yes/no) in 6MWT
Timepoint [11] 0 0
Baseline (week 0) to week 52

Eligibility
Key inclusion criteria
* Male or female.
* Age 12 years or above at the time of signing the informed consent.
* Confirmed diagnosis of sickle cell disease: Documentation of sickle cell disease (SCD) genotype (HbSS, HbSß0-thalassemia or other sickle cell syndrome variants) based on prior history of laboratory testing or screening test results from central laboratory. Molecular genotyping is not required. SCD genotype may be determined from the results of haemoglobin (Hb) electrophoresis, high-performance liquid chromatography (HPLC) or similar testing. Note that Hb electrophoresis is performed by the central laboratory at screening.
* Have 1-15 episodes of documented vaso occlusive crises (VOC) within the 12 months prior to screening. Documentation must exist in the participant's medical record prior to randomisation. Events based solely on participant recall without supporting documentation should not be counted towards eligibility.
* Hb greater than or equal to (=) 5.0 and less than or equal to (=) 10.0 g/dL (greater than or equal to (=) 50 and less than or equal to (=) 100 g/L) at screening.
Minimum age
12 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* More than 15 VOCs within the past 12 months prior to screening documented in the participant's medical record. Events based solely on participant recall without supporting documentation should not be counted towards eligibility.
* Use of voxelotor or similar agent within 28 days prior to starting study treatment or anticipated need for this agent during the study.
* Use of a selectin antagonist (e.g., crizanlizumab, monoclonal antibody or small molecule) within 28 days or 5 half-lives (whichever is longer) prior to starting study treatment or anticipated need for such agents during the study.
* Receiving regularly scheduled blood (RBC) transfusion therapy (also termed chronic, prophylactic, or preventive transfusion) or greater than or equal to 6 transfusion events in the previous 12 months (i.e., an average of 1 transfusion event every 60 days).
* Participants who have received an RBC transfusion for any reason within 60 days of the screening period or 60 days of the randomisation day are only eligible if HbA (adult haemoglobin) less than 10% by Hb electrophoresis is documented prior to starting study treatment.
* Receiving or use of concomitant medications that are strong inducers of CYP3A4 (cytochrome p450 3a4) within 2 weeks of starting study treatment or anticipated need for such agents during the study.
* Use of erythropoietin or other haematopoietic 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 (e.g., haematopoietic cell transplant, gene modification therapy).
* Hepatic dysfunction characterized by:

* Alanine aminotransferase (ALT) greater than 4.0 × upper limit of normal (ULN) or
* Direct bilirubin greater than 3.0 × ULN.
* Participants who are not taking or are unable to take antimalarial prophylaxis at the time of consent and during the study if they live in areas of endemic malaria where prophylaxis is recommended.
* Severe renal dysfunction (estimated glomerular filtration rate [eGFR] at screening, calculated by the central laboratory greater than 30 mL/min/1.73 m^ 2) or on chronic dialysis.
* Travelled distance on standardized 6MWT below 100m at screening.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
16/12/2024
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
22/09/2028
Actual
Sample size
Target
408
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 0 0
Prince of Wales Hospital - Randwick
Recruitment hospital [3] 0 0
Monash Health - Clayton
Recruitment hospital [4] 0 0
Fiona Stanley Hospital - Haemophilia and Haemostasis Centre - Murdoch
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2031 - Randwick
Recruitment postcode(s) [3] 0 0
3168 - Clayton
Recruitment postcode(s) [4] 0 0
6150 - Murdoch
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
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Arkansas
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California
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Colorado
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Delaware
Country [7] 0 0
United States of America
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District of Columbia
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Florida
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Georgia
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Illinois
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Louisiana
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Massachusetts
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Minnesota
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Missouri
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Nebraska
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Nevada
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New Jersey
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New York
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North Carolina
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Ohio
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Oklahoma
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Pennsylvania
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Tennessee
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Texas
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Virginia
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Washington
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Belgium
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Bruxelles
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Belgium
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Edegem
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Leuven
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Pernambuco
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SP
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São Paulo
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São
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Brazil
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Rio de Janeiro
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Antioquia
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Medellin
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Paris
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Athens
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Ioannina
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Thessaloniki
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Kerala
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India
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Maharashtra
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India
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Orissa
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India
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Telangana
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India
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Uttar Pradesh
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India
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New Delhi
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Italy
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Torino
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Italy
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Brescia
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Italy
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Catania
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Italy
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Modena
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Italy
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Monza
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Italy
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Naples
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Italy
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Padova
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Italy
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Palermo
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Italy
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Verona
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Lebanon
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Tripoli
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Netherlands
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Den Haag
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Rotterdam
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Utrecht
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Al Ahsa
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Dhahran
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Riyadh
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Sevilla
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Turkey
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Ankara
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Turkey
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Mersin
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United Kingdom
State/province [87] 0 0
Cambridge
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United Kingdom
State/province [88] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novo Nordisk A/S
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Transparency (dept. 2834)
Address 0 0
Novo Nordisk A/S
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Novo Nordisk
Address 0 0
Country 0 0
Phone 0 0
(+1) 866-867-7178
Fax 0 0
Email 0 0
clinicaltrials@novonordisk.com
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
According to the Novo Nordisk disclosure commitment on novonordisk-trials.com
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://novonordisk-trials.com


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT06612268