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 0835 or +27 21 938 0967
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202102669041711 Date of Registration: 23/02/2021
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Resolution of Sickle Cell Leg Ulcers with Voxelotor (RESOLVE)
Official scientific title A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial To Evaluate the Efficacy of Voxelotor for the Treatment of Leg Ulcers in Patients with Sickle cell Disease
Brief summary describing the background and objectives of the trial This study is a Phase 3, multicenter, randomized, double-blind, placebo-controlled trial to evaluate the efficacy of voxelotor for the treatment of leg ulcers in participants with sickle cell disease (SCD). The primary objective of this study is to assess the effect of voxelotor and SOC compared to placebo and SOC on leg ulcer healing in participants ≥ 12 years of age with SCD, as measured by the proportion of participants achieving resolution of target ulcer(s) in each treatment group by Week 12. The secondary objectives of this study are to evaluate the effect of voxelotor and SOC compared to placebo and SOC on: • Time to resolution of target ulcer(s) • Change in total surface area of target ulcer(s) • Incidence of new ulcers The exploratory objectives will assess the effect of voxelotor and SOC compared to placebo in addition to SOC (or open-label voxelotor and SOC, where applicable) on: • Correlation between change in hemoglobin (Hb) and target ulcer(s) healing • Correlation between change in hemolytic parameters (% reticulocytes, indirect bilirubin, lactate dehydrogenase [LDH]) and target ulcer(s) healing • Health-related quality of life (HRQOL) using patient-reported outcome (PRO) measures, when available (pending translation and cultural validation requirements) o Patient-Reported Outcome Measurements Information System (PROMIS) Pediatric Profile-37 v2.0/PROMIS-43 v2.1), which measures Physical Functioning, Pain Interference, Pain Behavior, Fatigue, Anxiety, Depression, and Ability to Participate in Social Roles and Activities) o Visual analog scale (VAS) assessment of pain level linked to target ulcer(s) o Patient Global Impression of Change (PGIC) • Clinician Global Impression of Change (CGIC) The safety objective is to assess the safety and tolerability of voxelotor compared to placebo based on adverse events (AEs), clinical laboratory tests, physical examinations, vital signs, and other clinical measures (eg, discontinuations due to AEs, dose reductions).
Type of trial RCT
Acronym (If the trial has an acronym then please provide) RESOLVE
Disease(s) or condition(s) being studied Genetic Diseases,Paediatrics
Sub-Disease(s) or condition(s) being studied
Purpose of the trial Treatment: Drugs
Anticipated trial start date 07/09/2021
Actual trial start date
Anticipated date of last follow up 26/06/2023
Actual Last follow-up date
Anticipated target sample size (number of participants) 80
Actual target sample size (number of participants)
Recruitment status Not yet 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
Factorial: participants randomly allocated to either no, one, some or all interventions simultaneously Randomised Stratified allocation where factors such as age, gender, center, or previous treatment are used in the stratification Allocation was determined by the holder of the sequence who is situated off site Masking/blinding used Care giver/Provider,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Voxelotor During the Randomized Treatment Period, participants will be randomized in a 1:1 ratio to receive 1500 mg of voxelotor once daily (administered as three 500 mg tablets) or matching placebo for 12 weeks. The approximate study duration for an individual participant includes the Screening Period (within 28 days), a Run-in Period of 2 weeks, a Randomized Treatment Period of 12 weeks, an Open label Treatment Period of 12 weeks, and a Follow-up Period/EOS visit (4 weeks [± 7 days] after the last dose of study drug). From Screening through Follow-up, total participation in this study for an individual participant may last from approximately 31 weeks to up to 34 weeks. Participants will continue to be followed for efficacy and safety through at least the endpoint visit (Week 12) regardless of treatment discontinuation. The study will end when the last participant’s last visit occurs. During the Randomized Treatment Period, participants will be randomized in a 1:1 ratio to receive 1500 mg of voxelotor once daily (administered as three 500 mg tablets) or matching placebo for 12 weeks. In this study, all participants will receive the standard of care (SOC) per protocol for SCD leg ulcers during the Run-in, Randomized Treatment, and Open-label Treatment periods. During the Open-label Period, all participants will receive 1500 mg of voxelotor once daily (administered as three 500 mg tablets) for an additional 12 weeks 40
Control Group Placebo During the Randomized Treatment Period, participants will be randomized in a 1:1 ratio to receive 1500 mg of voxelotor once daily (administered as three 500 mg tablets) or matching placebo for 12 weeks. In this study, all participants will receive the standard of care (SOC) per protocol for SCD leg ulcers during the Run-in, Randomized Treatment, and Open-label Treatment periods. During the Open-label Period, all participants will receive 1500 mg of voxelotor once daily (administered as three 500 mg tablets) for an additional 12 weeks. The approximate study duration for an individual participant includes the Screening Period (within 28 days), a Run-in Period of 2 weeks, a Randomized Treatment Period of 12 weeks, an Open label Treatment Period of 12 weeks, and a Follow-up Period/EOS visit (4 weeks [± 7 days] after the last dose of study drug). From Screening through Follow-up, total participation in this study for an individual participant may last from approximately 31 weeks to up to 34 weeks. Participants will continue to be followed for efficacy and safety through at least the endpoint visit (Week 12) regardless of treatment discontinuation. The study will end when the last participant’s last visit occurs. This study is a Phase 4, multicenter, randomized, double-blind, placebo-controlled trial to evaluate the efficacy of voxelotor for the treatment of leg ulcers in participants with sickle cell disease (SCD). 40 Placebo
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Participants who meet all the following criteria will be eligible for enrollment in this study: 1. Male or female participants with documented diagnosis of SCD one sickle gene with 2 sickle cell genes [HbSS], sickle hemoglobin and one beta thalassemia gene [HbS/β0] thalassemia 2. Age 12 years and older 3. At least 1 cutaneous ulcer on the lower extremity (leg, ankle, or dorsum of foot) that meets the following criteria: • Duration: ≥ 2 weeks and < 6 months at Screening, and • Size: > 2 square centimeters (cm2) prior to randomization • Note: Participants with multiple ulcers are eligible for the study. For each participant, target ulcer(s) for evaluation in this study will be identified and tracked. To qualify as a target ulcer, the ulcer must meet the criteria above. 4. Participants, who if female and of child-bearing potential, agree to use highly effective methods of contraception from study start to 30 days after the last dose of study drug and who if male, agree to use barrier methods of contraception from study start to 30 days after the last dose of study drug. 5. Females of child-bearing potential are required to have a negative pregnancy test before the administration of study drug. 6. Written informed consent (≥ 18 years) or parental/guardian consent and participant assent (≥ 12–17 years) per International Ethics Committee (IEC) policy and requirements, consistent with International Council for Harmonisation (ICH) guidelines Participants meeting any of the following exclusion criteria will not be eligible for study enrollment: 1. Target ulcer(s) healed by ≥ 25% during the SOC Run-in prior to randomization Note: For participants with multiple ulcers, the participant is not eligible for the study if all target ulcers have healed by ≥ 25% during the SOC Run-in. 2. Active infection/purulence at ulcer site, or exposed tendon or bone at the ulcer site, based on Investigator’s clinical judgment 3. Current osteomyelitis at or near the ulcer site 4. Known vascular abnormalities that would preclude healing in the opinion of the Investigator (eg, pre-existing severe arterial insufficiency in the affected limb) 5. Serum albumin < 2.0 g/dL 6. Red blood cell (RBC) transfusion within 60 days of initiation of study drug 7. Receiving regularly scheduled RBC transfusion therapy (also termed chronic, prophylactic, or preventive transfusion) during the study 8. Planned elective surgery within the next 6 months 9. Anemia due to bone marrow failure (eg, myelodysplasia) 10. Absolute reticulocyte count < 100 × 109/L 11. Screening alanine aminotransferase (ALT) > 4 × upper limit of normal (ULN) 12. Severe renal dysfunction (estimated glomerular filtration rate [eGFR] < 30 mL/min/1.73 m2 by Schwartz formula) or is on chronic dialysis 13. Clinically significant bacterial, fungal, parasitic, or viral infection that requires therapy: • Participants with acute bacterial infection requiring systemic antibiotic use should delay Screening/enrollment until the course of antibiotic therapy has been completed • Participants with known active hepatitis A, B, or C or who are known to be human immunodeficiency virus (HIV) positive • Participants with active SARS-CoV-2 infection (COVID-19) 14. Females who are breast-feeding or pregnant 15. History of hematopoietic stem cell transplant or gene therapy 16. Participated in another clinical trial of an investigational product (or medical device) within 30 days or 5 half-live 80 and over: 80+ Year,Adolescent: 13 Year(s)-17 Year(s),Adult: 18 Year(s)-44 Year(s),Aged: 65 Year(s)-79 Year(s),Middle Aged: 45 Year(s)-64 Year(s) 12 Year(s) 100 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 27/05/2021 KEMRI CCR SERU for Dr Ogutu
Ethics Committee Address
Street address City Postal code Country
Off Raila Odinga Way 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 08/06/2021 Gertrudes Childrens Hospital Ethical Review Board
Ethics Committee Address
Street address City Postal code Country
34 Muthaiga road 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 28/10/2021 KEMRI CCR SERU for Dr Nduba
Ethics Committee Address
Street address City Postal code Country
Off Raila Odinga Way 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 16/08/2021 KEMRI CCR SERU for Dr Oyieko
Ethics Committee Address
Street address City Postal code Country
Off Raila Odinga Way Nairobi 00200 Kenya
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome The primary objective of this study is to assess the effect of voxelotor and SOC compared to placebo and SOC on leg ulcer healing in participants ≥ 12 years of age with SCD, as measured by the proportion of participants achieving resolution of target ulcer(s) in each treatment group by Week 12 Week 12
Secondary Outcome The secondary objectives of this study are to evaluate the effect of voxelotor and SOC compared to placebo and SOC on: • Time to resolution of target ulcer(s) • Change in total surface area of target ulcer(s) • Incidence of new ulcers week 12
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Strathmore University Kisumu-Kakamega Road, Kondele Kisumu 40123 Kenya
Lagos University Teaching Hospital Haematology PO Box 12003 Surulere 101014 Nigeria
Barau Dikko Teaching Hospital Kaduna State University Lafiya Road Kaduna Nigeria
University of Nigeria Kwame Nkuruma Way Enugu Nigeria
KEMRI CRDR Kenyatta National Hospital Off Hospital Road Nairobi 00100 Kenya
Haematology and Blood Transfusion Unit Department of Human Pathology University of Nairobi Nairobi 00202 Kenya
KEMRI CCR Butere County Hospital Butere County hospital, along Shaitsala-Sabatia Road Butere 50101 Kenya
Aminu Kano Teaching Hospital Zaria Road Kano 700233 Nigeria
University of Abuja Permanent site, Sultan Maccido Road Abuja 900105 Nigeria
University of Calabar Teaching Hospital Court Road Duke Town Calabar 540281 Nigeria
FUNDING SOURCES
Name of source Street address City Postal code Country
Global Blood Therapeutics 181 Oyster Point Blvd South San Francisco CA 94080 United States of America
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Global Blood Therapeutics Inc 181 Oyster Point Blvd South San Francisco CA 94080 United States of America Commercial Sector/Industry
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Bernhards Ragama Ogutu ogutu6@gmail.com +254733813613 Kisumu-Kakamega Road, Kondele
City Postal code Country Position/Affiliation
Kisumu Kenya National Principal Investigator
Role Name Email Phone Street address
Scientific Enquiries Carolyn Hoppe choppe@gbt.com +657417741 181 Oyster Point Blvd
City Postal code Country Position/Affiliation
South San Francisco CA 94080 United States of America Senior Medical Director
Role Name Email Phone Street address
Public Enquiries Theresa Thuener tthuener@gbt.com +6507417710 181 Oyster Point Blvd
City Postal code Country Position/Affiliation
South San Francisco CA 94080 United States of America Clinical Operations Study Oversight
Role Name Email Phone Street address
Principal Investigator Dr. Halima bello Manga mamanzara@yahoo.com 02348033470592 Lafiya Road
City Postal code Country Position/Affiliation
Kaduna 800212 Nigeria National Principal Investigator
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Trial result summaries will be shared when the final clinical study report is available. The method of sharing the information is still to be determined across the entire program of studies. Clinical Study Report,Informed Consent Form,Statistical Analysis Plan,Study Protocol When the Clinical Study Report is final To be confirmed
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 - 14/11/2025
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information