This study is a randomized, placebo-controlled, double-blind, multicenter Phase 2/3 study of patients, age 12 to 65 years, with sickle cell disease (SCD).

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] - Hemic and Lymphatic Diseases [C15]

Trial duration

16 Dec 2021 → ongoing

Decision date (initial)

2024-07-23

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Forma Therapeutics, Inc.

External identifiers

EU CT number

2024-511535-97-00

EudraCT number

2020-003884-25

ClinicalTrials.gov

NCT04624659

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Efficacy

• To assess the efficacy of Etavopivat in adolescents and adults with SCD as compared to placebo as measured by improvement in hemoglobin (Hb)
• To assess the efficacy of Etavopivat as compared to placebo on the annualized vaso-occlusive crisis (VOC) rate

Secondary objectives 3

1. • To measure the effects of Etavopivat on clinical measures and sequelae of hemolysis
2. • To assess changes in fatigue of adult sickle cell patients taking etavopivat
3. • To evaluate the effects of Etavopivat on the sequelae of VOC

Conditions and MedDRA coding

sickle cell disease (SCD)

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 7

1. 1) Provision of consent
2. 2) Patient has a confirmed diagnosis of sickle cell disease
3. 3) 2-15 episodes of documented vaso-occlusive crises in the past 12 months
4. 4) Hemoglobin ≥ 5.5 and ≤ 10.5 g/dL (≥ 55 and ≤ 105 g/L) during screening
5. 5) Patients taking hydroxyurea, must demonstrate a stable dose for at least 90 days prior to start of study treatment
6. 6) Female patients of childbearing potential must use acceptable methods of contraception; male patients are willing to use acceptable methods of contraception
7. 7)Patients on crizanlizumab or L-glutamine oral powder (Endari®) 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 (i.e., no changes to the dose except for changes to weight or for safety reasons) • Have been ≥ 80% compliant with the planned regimen during the 12 months prior to the time of consent • Meet the VOC eligibility requirement in Inclusion Criterion 4.

Exclusion criteria 15

1. Medical Conditions 1) More than 15 vaso-occlusive crises within the past 12 months prior to screening
2. 2) Female who is breast feeding or pregnant
3. 3) Hepatic dysfunction characterized by: - Alanine aminotransferase (ALT) > 4.0 × upper limit of normal (ULN) OR - Direct bilirubin > 3.0 × ULN
4. 4) Known HIV positive
5. 5) Active hepatitis B or hepatitis C infection
6. 6) Severe renal dysfunction or on chronic dialysis
7. 7) 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 clinically significant arrhythmias - Symptomatic pulmonary hypertension
8. 8) History of overt clinical stroke within previous 2 years or any history of an intracranial hemorrhage
9. 9) History of deep venous thrombosis requiring systemic anticoagulation therapy for ≥ 6 weeks, occurring within 6 months prior to Day 1 of study treatment. Note: patients on ≥ 6 months of chronic or prophylactic anti-coagulation therapy are allowed on study.
10. Prior/Concomitant Therapy 1) Patients receiving regularly scheduled blood (RBC) transfusion therapy (also termed chronic, prophylactic, or preventive transfusion)
11. 2) Receiving or use of concomitant medications that are strong inducers of CYP3A4/5 within 2 weeks of starting study treatment or anticipated need for such agents during the study
12. 3) Use of voxelotor within 28 days prior to starting study treatment or anticipated need for this agent during the study
13. 4) Use of an experimental selectin antagonist (e.g., monoclonal antibody or small molecule) within 28 days of starting study treatment or anticipated need for such agents during the study
14. 5) Uso de eritropoyetina u otro tratamiento con factor de crecimiento hematopoyético dentro de los 28 días posteriores al inicio del tratamiento del estudio o la necesidad anticipada de dichos agentes durante el estudio.
15. 6) Receipt of prior cellular-based therapy (e.g., hematopoietic cell transplant, gene modification therapy)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. • Hb response rate at Week 24 (increase of > 1 g/dL [> 10 g/L] from baseline) during the blinded treatment period
2. • Annualized VOC rate during the 52-week blinded treatment period based on adjudicated VOC review

Secondary endpoints 4

1. 1. Change from baseline in Hb at Week 52 during the blinded treatment period
2. 2. Change in SCD-related clinical laboratory measurements from baseline at Week 24 during the blinded treatment period in: o Absolute reticulocyte count, o Indirect bilirubin, and o Lactate dehydrogenase (LDH)
3. 3. Change from baseline in Patient-Reported Outcome Measurement Information System (PROMIS) Fatigue Scale in adult patients at Week 52 during the blinded treatment period
4. 4. Time to first VOC during the blinded treatment period

Investigational products

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

Test 2

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 7

Locations

5 EU/EEA countries · 21 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 62 files

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

Application history

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