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

NCT06198712 | Recruiting Phase 2 FDA Drug

• 3 other identifiers: 4202-HEM-2022022-001689-362024-519881-32
• Study Type: interventional
• Target: 95
• Locations: 7 countries
• Sites: 18

Brief Summary

The purpose of this study is to evaluate the pharmacokinetics and safety of etavopivat in paediatric participants with sickle cell disease (SCD). Participants will receive etavopivat and will be enrolled in a staggered manner, starting with the oldest age group and followed sequentially by younger cohorts after review of pharmacokinetic and safety data from the preceding cohort. All participants will undergo a 24-week primary treatment period followed by a 72-week extension treatment period to further evaluate long-term safety and pharmacokinetics of etavopivat. The total duration of the study will be approximately 96 weeks.

Conditions

Sickle Cell Disease

Outcome Measures

Primary Outcomes (11)

• 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 Outcomes (10)

• 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

Study Arms (4)

Cohort 1: Etavopivat (12 to less than [<] 18 years)

EXPERIMENTAL

Participants aged 12 to less than 18 years with sickle cell disease will receive etavopivat to evaluate pharmacokinetics and safety in this age group.

Drug: Etavopivat

Cohort 2: Etavopivat (6 to <12 years)

EXPERIMENTAL

Participants aged 6 to less than 12 years with sickle cell disease will receive etavopivat to evaluate pharmacokinetics and safety in this age group.

Drug: Etavopivat

Cohort 3: Etavopivat (2 to <6 years)

EXPERIMENTAL

Participants aged 2 to less than 6 years with sickle cell disease will receive etavopivat to evaluate pharmacokinetics and safety in younger children.

Drug: Etavopivat

Cohort 4: Etavopivat (6 months to <2 years)

EXPERIMENTAL

Participants aged 6 months to less than 2 years with sickle cell disease will receive etavopivat to evaluate pharmacokinetics and safety in infants.

Drug: Etavopivat

Interventions

Etavopivat DRUG

Participants will receive oral tablets or granules of etavopivat once daily.

Cohort 1: Etavopivat (12 to less than [<] 18 years); Cohort 2: Etavopivat (6 to <12 years); Cohort 3: Etavopivat (2 to <6 years); Cohort 4: Etavopivat (6 months to <2 years)

Eligibility Criteria

• Age: 6 Months - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Type of Participant and Disease Characteristics
• Patient's parent, legal guardian, or legal representative has provided documented informed consent and patients have provided age-appropriate assent
• 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
• 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.
• Hemoglobin ≥ 5.5 and lesser than or equal to (≤) 10.5 grams per deciliter (g/dL)
• Pediatric patients with severe SCD, as defined by at least 1 of the following:
• 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).

You may not qualify if:

• Medical Conditions
• Female who is breastfeeding or pregnant
• More than 15 VOCs within the 12 months prior to starting study treatment that required a hospital, emergency room (ER), or clinic visit
• Hospitalized for sickle cell crisis or other vaso-occlusive event occurring in the 14 days prior to starting study treatment
• Abnormal TCD in the 12 months prior to starting study treatment
• Prior/Concomitant Therapy
• Patients receiving regularly scheduled blood (RBC) transfusion therapy (also termed chronic, prophylactic, or preventive transfusion)
• Received any blood products within 30 days of starting study treatment
• Receiving or use of concomitant medications that are strong inducers of cytochrome P450 (CYP) 3A4/5 within 2 weeks of starting study treatment
• Use of voxelotor within 28 days prior to starting study treatment or anticipated need for this agent during the study
• 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
• Receipt of prior cellular based therapy (eg, hematopoietic cell transplant, gene modification therapy)

Sponsors & Collaborators

• Forma Therapeutics, Inc.: lead
• Novo Nordisk A/S. This study is currently undergoing a sponsor transition from Forma Therapeutics, Inc. to Novo Nordisk A/S.: collaborator

Study Sites (18)

The Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

COMPLETED

HCL-HOPITAL LYON SUD_Institut d'Hématologie et d'Oncologie Pédiatrique (IHOPe)

Lyon, 69008, France

NOT YET RECRUITING

APHP - Centre de Référence des Syndromes

Paris, 75019, France

NOT YET RECRUITING

Centre Hospitalier Universitaire de Rouen-Hopital Charles Nicolle

Roeun, 76031, France

NOT YET RECRUITING

KEMRI CRDR Siaya Clinical Research Annex, Country Referral Hospital

Siaya, Siaya County, 40600, Kenya

RECRUITING

KEMRI-Walter-Reed Kericho

Kericho, 20200, Kenya

RECRUITING

Kombewa Clinical Research Centre

Kisumu, 40100, Kenya

RECRUITING

Ahero Clinical Trials Unit

Kisumu, 40101, Kenya

RECRUITING

American University of Beirut Medical center

Beirut, 1107 2020, Lebanon

RECRUITING

Hospital Nini

Tripoli, 113-6044, Lebanon

RECRUITING

University of Nigeria Teaching Hospital (UNTH)

Ituku-Ozalla, Enugu State, 400001, Nigeria

RECRUITING

Lagos University Teaching Hospital, Lagos

Lagos, 102215, Nigeria

RECRUITING

Aminu Kano Teaching Hospital (AKTH)

Tarauni, 700101, Nigeria

RECRUITING

Hacettepe University pediatric hematology

Ankara, 06100, Turkey (Türkiye)

COMPLETED

Acıbadem Adana Hastanesi

Seyhan, 1130, Turkey (Türkiye)

COMPLETED

Guys and St Thomas NHS Foundation Trust / Evelina Childrens Hospital

London, SE1 7EH, United Kingdom

RECRUITING

King's College Hospital - Alex Mowat Research Hub

London, SE5 9RS, United Kingdom

RECRUITING

Manchester Royal Infirmary_1

Manchester, M13 9WL, United Kingdom

RECRUITING

MeSH Terms

Conditions

Anemia, Sickle Cell

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Clinical Transparency (dept. 2834)

  Novo Nordisk A/S

  STUDY DIRECTOR

Central Study Contacts

Novo Nordisk

CONTACT

(+1) 866-867-7178; clinicaltrials@novonordisk.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 27, 2023
• First Posted: January 10, 2024
• Study Start: January 12, 2023
• Primary Completion (Estimated): February 23, 2028
• Study Completion (Estimated): August 8, 2029
• Last Updated: September 18, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will share

Locations

LE (2); FR (3); NG (3); CA (1); KE (4); TU (2); GB (3)