Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202209604592389 Date of Approval: 07/09/2022
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title A Single Arm, Open Label, Phase 1/2 Study to Evaluate the Pharmacokinetics and Safety of Etavopivat in Pediatric Patients with Sickle Cell Disease
Official scientific title A Single Arm, Open Label, Phase 1/2 Study to Evaluate the Pharmacokinetics and Safety of Etavopivat in Pediatric Patients with Sickle Cell Disease
Brief summary describing the background and objectives of the trial This study is a single arm, open label, phase 1/2 PK and safety study in patients with SCD, aged 12 to < 18 years. The study will enroll up to 50 patients. The study objectives to assess PK and safety will be met after all subjects complete 24 weeks of treatment, discontinue or withdraw, with additional follow-up in the 72-week extension treatment period. Patients will be offered continued access to etavopivat following completion of this trial on a separate post-trial expanded access study.
Type of trial CCT
Acronym (If the trial has an acronym then please provide)
Disease(s) or condition(s) being studied Haematological Disorders
Sub-Disease(s) or condition(s) being studied
Purpose of the trial Treatment: Drugs
Anticipated trial start date 02/01/2023
Actual trial start date 24/08/2023
Anticipated date of last follow up 30/12/2025
Actual Last follow-up date
Anticipated target sample size (number of participants) 95
Actual target sample size (number of participants)
Recruitment status Recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Crossover: all participants receive all interventions in different sequence during study Non-randomised Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Etavopivat 400mg Once Daily 96 weeks Etavopivat is a potent, selective, orally bioavailable, small-molecule activator of erythrocyte pyruvate kinase 50
Control Group Etavopivat 400mg Once daily 96 weeks Etavopivat is a potent, selective, orally bioavailable, small-molecule activator of erythrocyte pyruvate kinase 0 Uncontrolled
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
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. 2. Hemoglobin ≥ 5.5 and < 10.5 g/dL 3. Adolescent patients with severe SCD, as defined by at least 1 of the following: • Two or more VOCs in the past 12 months, defined as a previously documented episode of acute chest syndrome (ACS) or acute painful crisis (for which there was no explanation other than VOC) which required prescription or healthcare professional-instructed use of analgesics for moderate to severe pain • Hospitalization for any SCD-related complication in the last 12 months • 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, but not currently being treated with chronic transfusion therapy. Conditional TCD is defined as a TAMMV of 170-199 cm/s by TCD or 155-184 cm/s by imaging TCD (TCDi). 4. For participants taking HU, the dose of HU (mg/kg) must be stable (no more than a 20% change in dosing) for at least 90 days prior to start of study treatment with no anticipated need for dose adjustments during the study, in the opinion of the Investigator 5. Patients on crizanlizumab or L-glutamine 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 (ie, no changes to the dose except for changes to weight or for safety reasons) • For patients on crizanlizumab, have been ≥ 80% compliant with the planned regimen during the 12 months prior to the time of consent Medical Conditions 1. More than 10 VOCs within the past 12 months that required a hospital, emergency room(ER), or clinic visit 2. Hospitalized for sickle cell crisis or other vaso-occlusive event within 14 days of Screening 3. Abnormal TCD in the prior 12 months Prior/Concomitant Therapy 4. Patients receiving regularly scheduled blood (RBC) transfusion therapy (also termed chronic, prophylactic, or preventive transfusion) 5. Received any blood products within 30 days of starting study treatment 6. Receiving or use of concomitant medications that are strong inducers of cytochrome P450 (CYP) 3A4/5 within 2 weeks of starting study treatment 7. Use of voxelotor within 28 days prior to starting study treatment or anticipated need for this agent during the study 8. 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 9. Receipt of prior cellular based therapy (eg, hematopoietic cell transplant, gene modification therapy) Adolescent: 13 Year-18 Year,Child: 6 Year-12 Year 12 Year(s) 18 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 27/01/2023 National Health Research Ethics Committee Nigeria
Ethics Committee Address
Street address City Postal code Country
PMB 083, Abuja Abuja 900243 Nigeria
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 24/05/2023 Lagos University Teaching Hospital
Ethics Committee Address
Street address City Postal code Country
Central Administration Block - Idi-Araba Lagos 100271 Nigeria
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 30/12/2022 UNIVERSITY OF NIGERIA TEACHING HOSPITAL
Ethics Committee Address
Street address City Postal code Country
ITUKU OZALLA PMB 01129 ENUGU NIGERIA Enugu 400001 Nigeria
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 24/03/2023 Aminu Kanu Teaching hospital Ethics Committee
Ethics Committee Address
Street address City Postal code Country
P. M. B. 3452 ZARIA ROAD KANO None Nigeria
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 21/12/2022 KEMRI SERU
Ethics Committee Address
Street address City Postal code Country
P.O. Box 54840 Nairobi 00200 Kenya
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 14/07/2023 KEMRI SERU
Ethics Committee Address
Street address City Postal code Country
P.O. Box 54840 Nairobi 00200 Kenya
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 18/07/2023 KEMRI SERU
Ethics Committee Address
Street address City Postal code Country
P.O. Box 54840 Nairobi 00200 Kenya
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 09/02/2023 KEMRI SERU
Ethics Committee Address
Street address City Postal code Country
P.O. Box 54840 Nairobi 00200 Kenya
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome To assess the PK of etavopivat in patients with SCD Through out the study
Primary Outcome To assess the safety and tolerability of etavopivat during the 24-week primary treatment period Through out the study
Secondary Outcome To assess the safety and tolerability of etavopivat during the 72-week treatment extension period End of the study
Secondary Outcome To assess the effects of etavopivat on hemoglobin (Hb) response Week 12 and 24
Secondary Outcome To describe the occurrence of VOCs in enrolled patients Week 24
Secondary Outcome To assess changes in fatigue of patients with SCD taking etavopivat Week 12 and 24
Secondary Outcome To assess changes in cerebral blood flow in patients with SCD taking etavopivat Week 72
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
University of Nigeria Hematology Department 1 Unth Road Ituku Ozalla Enugu State Nigeria
Lagos University Teaching Hospital Ishaga Road, Idi-Araba Lagos Nigeria
Ahero Clinical Trials Unit P.O Box 2254 Nairobi Kenya
KEMRI Kombewa PO Box 54 Kisumu Kenya
KEMRI Walter Reed Kericho PO Box 1357 Kericho Kenya
Aminu Kano Teaching Hospital 2 Zaria Road Kano Nigeria
KEMRI Siaya Clinical Trials Annex Siaya County referral Hospital Siaya None Kenya
FUNDING SOURCES
Name of source Street address City Postal code Country
Forma Therapeutics 300 North Beacon Street Watertown United States of America
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Forma Therapeutics Inc 300 North Beacon Street Watertown 02472 United States of America Commercial Sector/Industry
COLLABORATORS
Name Street address City Postal code Country
IQVIA Landmark Plaza 13th Floor Argwins Kodhek Road Nairobi 00606 Kenya
CONTACT PEOPLE
Role Name Email Phone Street address
Scientific Enquiries Cameron Trenor 4202-202Clinical@formarx.com +18572092374 300 North Beacon Street Suite 501
City Postal code Country Position/Affiliation
Watertown United States of America Sponsor
Role Name Email Phone Street address
Public Enquiries Michelle Botha michelle.botha@quintiles.com +27126712334 Pretoria
City Postal code Country Position/Affiliation
Pretoria South Africa Regulatory
Role Name Email Phone Street address
Principal Investigator Bernhards Ogutu ogutu@gmail.com +254733812613 Ahero Clinical Trials Unit
City Postal code Country Position/Affiliation
Kisumu Kenya Principle Investigator
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes All IDP will be stripped of identifiers and may be available upon request Informed Consent Form,Study Protocol Approximately 18 months after trial completion N/A
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information