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.: PACTR202208531640912 Date of Approval: 10/08/2022
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title A Phase 2/3 Study in Adult and Pediatric Participants with Sickle Cell Disease (SCD)
Official scientific title A Phase 2/3, Randomized, Multicenter Study of GBT021601 Administered Orally to Participants with Sickle Cell Disease and an Open- Label Pharmacokinetics Study in Pediatric Participants with Sickle Cell Disease.
Brief summary describing the background and objectives of the trial This is a three-part, multicenter, Phase 2/3 study of orally administered GBT021601 in participants with sickle cell disease (SCD). Part A will evaluate the safety, tolerability, and efficacy of GBT021601 in adult participants with SCD to determine an optimal dose. Part B will evaluate the efficacy of GBT021601 versus placebo in adult and pediatric participants with SCD for 48 weeks. Part C will evaluate the pharmacokinetics (PK) and safety of single and multiple doses (MD) of open-label single arm GBT021601 administered to pediatric participants.
Type of trial RCT
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 30/06/2022
Actual trial start date
Anticipated date of last follow up 31/10/2026
Actual Last follow-up date
Anticipated target sample size (number of participants) 480
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
Parallel: different groups receive different interventions at same time during study Randomised Permuted block randomization Allocation was determined by the holder of the sequence who is situated off site Masking/blinding used Care giver/Provider,Outcome Assessors,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Drug GBT021601 Part A Initially, participants will be randomized 1:1 to 100 mg and 150 mg daily. Upon review of the 150 mg safety data from at least 6 participants, there will be 1:1:1 randomization: 100 mg, 150 mg, and up to 200 mg. Participants will then receive maintenance once daily doses through Week 12. Part B Following the selection of the optimal safe and effective dose from Part A of the study, Part B of the study will assess the efficacy and safety of 48 weeks of the optimal dose, compared to placebo Part C 100 mg dose in cohort C1, dose level for cohorts C2 to C4 to be determined based on emerging data Part A The maximum duration of the study for adult participants in Part A is approximately 28weeks. This includes a 28-day Screening period, up to a 12-week Treatment period. All participants will be followed by an EOS Visit 8 weeks after completion of treatment. Part B The maximum duration of the study for participants in Part B is approximately 60 weeks. This includes a 28-day Screening period and a 48-week Treatment period. All participants will be followed by an EOS Visit 8 weeks after completion of treatment. Part C The maximum duration of the study for pediatric participants is approximately 23 weeks. This includes a 35-day Screening period and up to an approximately 10-week Treatment period. All participants will be followed by an EOS Visit 8 weeks after completion of treatment Tablets which contain GBT021601 drug substance 240
Control Group Drug GBT021601 Following the selection of the optimal safe and effective dose from Part A of the study, Part B of the study will assess the efficacy and safety of 48 weeks of the optimal dose, compared to placebo Part B of the study will assess the efficacy and safety of 48 weeks of the optimal dose, compared to placebo Placebo Tablets identical to Drug GBT021601 240 Placebo
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Inclusion Criteria: Part A, Part B, and Part C: • Male or female with SCD • Participants with stable hemoglobin value • Participants on HU should be on stable dose for at least 90 days prior to signing ICF Part B: • Participants with SCD ages 12 to 65 years, inclusive • Participants with more than or equal to 2 and less than or equal to 10 VOCs inclusive, within 12 months of Screening Part A, Part B, and Part C: • Participants who had more than 10 VOC within 12 months of screening • Female participant who is breastfeeding or pregnant • Participants who receive RBC transfusion therapy regularly or received an RBC transfusion ---for any reason within 90 days of Day 1 • Participants hospitalized for sickle cell crisis or other vaso-occlusive event within 14 days of signing the ICF Adolescent: 13 Year-18 Year,Adult: 19 Year-44 Year,Child: 6 Year-12 Year,Infant: 1 Month-23 Month,Middle Aged: 45 Year(s)-64 Year(s),Preschool Child: 2 Year-5 Year 6 Month(s) 65 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 27/04/2022 National Health Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
11th Floor Federal Secretariat Complex, Phase 3, Ahmadu Bello way Abuja 900288 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 24/06/2022 Gertudes Children Hospital Ethics Review Committee
Ethics Committee Address
Street address City Postal code Country
34, Muthaiga Road, Muthaiga Nairobi 42325-001 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 06/06/2022 Aminu Kano Teaching Hospital Ethics Committee
Ethics Committee Address
Street address City Postal code Country
No 2 Zaria Road, Kano State Kano 700223 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 07/06/2022 Lagos University Teaching Hospital Health Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Ishaga Road, Idi-Araba Lagos 100254 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
No 14/08/2022 Kenya Medical Research Institute KEMRI National Ethics Review Committee
Ethics Committee Address
Street address City Postal code Country
P.O Box 54840 Off Mbagathi 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
No 21/08/2022 Joint Clinical Research Center Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Plot 101 Entebbe Road, 10005 Kampala, Central Kampala 10101 Uganda
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome 1. Part A [ Time Frame: Through week 12] Number of adult participants with change from baseline in hemoglobin (Hb) through week 12 2. Part B [ Time Frame: Through week 48] Proportion of participants with an increase from baseline of >1 g/dL in Hb at week 48 3. Part C [ Time Frame: Through Week 2] Assess the pharmacokinetics, while observing maximum concentration (Cmax) after a single dose 4. Part C [ Time Frame: Through Week 2] Assess the pharmacokinetics, while observing minimum concentration (Cmin) and maximum concentration after multiple dose administration For Part A - the time frame is through week 12 , Part B -the time frame is through week 48 , Part C- time frame is through week 2
Secondary Outcome 1. Part A [ Time Frame: Through week 12] Proportion of participants with an increase from baseline of >1 g/dL in Hb through Week12 2. Part B [ Time Frame: Through week 48] Annualized rate of vaso-occlusive crisis (VOC)through end of Week48 3. Part C [ Time Frame: Through Week 2] Change from baseline in Hb at MD Week 2 (Day 14). Part A Time Frame is Through week 12 , Part B Time Frame is Through week 48 , Part C Time Frame is Through week 2
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Lagos University Teaching Hospital Ishaga Road, Idi-Araba, Surulere 100254 Nigeria
Aminu Kano Teaching Hospital No 2 Zaria Road Kano city 700223 Nigeria
University of Ibadan University College Hospital College of Medicine, University of Ibadan Queen Elizabeth Road, Orita Mefa. Ibadan 200211 Nigeria
Kenya Medical Research Institute KEMRI/CRDR Clinical Research Annex. Kenyatta National Hospital, Off Hospital Road P.O. Box 47855-00100 Nairobi 00100 Kenya
KEMRI CRDR SIAYA SITE Kemri Siaya Clinical Research Annex Siaya County Referral Hospital Road Siaya 40600 Kenya
Center for Research in Therapeutic Sciences Strathmore University Medical Centre Ole Sangale Road. Nairobi 00200 Kenya
Gertrudes Childrens Hospital 34, Muthaiga Road, Muthaiga Nairobi 42325-001 Kenya
Tororo General Hospital Infectious Disease Research Collaboration 2c Nakasero Hill Road Kampala Uganda
Makerere University College of Health Sciences Mulago Hill Road, P.O Box 7072, Kyadondo Kampala Uganda
Mbale Regional Refferal Hospital Mbale Clinical Research Institute Plot 29-33, Pallisa Road Mbale Uganda
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
Xcene Research 1 Ogunsuji Close, S and B Tejuosho Estate, Off Allen Avenue Ikeja Nigeria
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Shehu Abdullahi Umar dr_suak@yahoo.com +2348028503832 No. 2 Zaria Road, Kano city, Kano State
City Postal code Country Position/Affiliation
Kano 700223 Nigeria National Principal Investigator
Role Name Email Phone Street address
Scientific Enquiries Eleanor Lisbon elisbon@gbt.com +16507811765 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 Jessica Guider jguider@gbt.com +16303642275 181 Oyster Point Blvd
City Postal code Country Position/Affiliation
South San Francisco CA 94080 United States of America Senior Clinical Trial Manager
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Plan to Share IPD: No. Progress will be shared at specific intervals defined per the protocol and at the end of the Study. Clinical Study Report,Informed Consent Form,Statistical Analysis Plan,Study Protocol N/A 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