A research study to evaluate how well etavopivat works in people with sickle cell disease - Hibiscus 2

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novo Nordisk A/S

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Trial duration

14 Oct 2025 → ongoing

Decision date (initial)

2025-03-18

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Novo Nordisk A/S

External identifiers

EU CT number

2023-509175-16-00

WHO UTN

U1111-1298-3431

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

To demonstrate superiority of treatment with etavopivat versus placebo in adolescents and adults with sickle cell disease

Secondary objectives 3

1. 1.To evaluate clinical efficacy measures of etavopivat treatment versus placebo in adolescents and adults with sickle cell disease
2. 3.To assess clinically meaningful improvement in fatigue and functional exercise capacity and Quality of Life measures of adolescents and adults with sickle cell disease taking etavopivat treatment compared to placebo
3. 2.To evaluate the improvement in functional exercise capacity in adolescents and adults with SCD taking etavopivat treatment compared to placebo

Conditions and MedDRA coding

Sickle cell disease

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-002924-PIP02-23

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Male or female
2. Age 12 years or above at the time of signing the informed consent
3. Confirmed diagnosis of sickle cell disease (SCD): Documentation of SCD genotype (HbSS, HbSβ0-thalassemia or other sickle cell syndrome variants) based on prior history of laboratory testing or screening test results from central laboratory.
4. Have 2−15 episodes of documented vaso-occlusive crises (VOCs) 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.
5. Hb ≥5.0 and ≤10.0 g/dL (≥50 and ≤100 g/L) at screening.

Exclusion criteria 11

1. Use of voxelotor or similar agent within 28 days prior to starting study treatment or anticipated need for this agent during the study
2. 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.
3. Receiving regularly scheduled blood (RBC) transfusion therapy (also termed chronic, prophylactic, or preventive transfusion) or ≥6 transfusion events in the previous 12 months (i.e., an average of 1 transfusion event every 60 days).
4. 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 Hb) <10% by Hb electrophoresis is documented prior to starting study treatment.
5. Receiving or use of concomitant medications that are strong inducers of CYP3A4 within 2 weeks of starting study treatment or anticipated need for such agents during the study.
6. 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.
7. Receipt of prior cellular-based therapy (e.g., haematopoietic cell transplant, gene modification therapy).
8. Hepatic dysfunction characterized by: Alanine aminotransferase (ALT) >4.0 × upper limit of normal (ULN) or Direct bilirubin >3.0 × ULN.
9. 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.
10. Severe renal dysfunction (estimated glomerular filtration rate [eGFR] at screening, calculated by the central laboratory <30 mL/min/1.73 m2) or on chronic dialysis.
11. Travelled distance on standardized 6-minute walking test below 100m at screening.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Number of adjudicated VOC events with a medical contact.

Secondary endpoints 10

1. Change in Hb >1 g/dL (yes/no)
2. Time to onset of first adjudicated VOC.
3. Change in standardised T-score on the PROMIS Fatigue 7a Scale.
4. Change in haemoglobin (Hb)
5. Change in lactate dehydrogenase (LDH)
6. Change in absolute reticulocyte count
7. Change in indirect bilirubin
8. Change in distance travelled during the 6-minute walking test (6MWT)
9. Participants achieving the threshold for clinically meaningful change (yes/no) in PROMIS fatigue scale 7a
10. Participants achieving the threshold for clinically meaningful change (yes/no) in 6MWT

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novo Nordisk A/S

Sponsor organisation

Novo Nordisk A/S

Address

Novo Alle 1

City

Bagsvaerd

Postcode

2880

Country

Denmark

Scientific contact point

Organisation

Novo Nordisk A/S

Contact name

EU Submission Hub

Public contact point

Organisation

Novo Nordisk A/S

Contact name

EU Submission Hub

Third parties 6

Locations

6 EU/EEA countries · 36 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 83 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications