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.: PACTR202508611698393 Date of Registration: 01/08/2025
Trial Status: Retrospective registration - This trial was registered after enrolment of the first participant
TRIAL DESCRIPTION
Public title A Phase I/II study of ITU512 in healthy participants and patients with sickle cell disease
Official scientific title A Phase I/II clinical study to investigate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of ITU512 in healthy participants and patients with sickle cell disease
Brief summary describing the background and objectives of the trial Sickle cell disease (SCD) is a life-threatening genetic disorder with the global burden residing in sub-Saharan Africa. SCD is caused by a single mutation in the β globin gene resulting in the production of an abnormal form of hemoglobin. Patients with SCD are protected at birth due to high levels of fetal hemoglobin (HbF), encoded by the γ globin gene. However, symptoms of SCD arise when expression of HbF declines, typically in the first year of life. ITU512, an orally available investigational compound, has been proven in pre-clinical studies to induce HbF expression, a therapeutic strategy which has been associated with improvement in clinical outcomes and increased survival in SCD patients. The purpose of this global Phase I/II study is to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary food effect of ITU512 including the fetal hemoglobin (HbF)-inducing capacity of ITU512. This will be the first evaluation of the potential therapeutic effect of ITU512. The study consists of a first-in-human Phase I study (Part 1) in healthy adult participants, and a Phase II study (Part 2) in adolescent and adult patients with sickle cell disease (SCD). Part 1 will comprise of Part 1A, Part 1B, and Part 1C. Part 2 will comprise of Part 2A, Part 2B and optional Part 2C extension. Part 1/Phase I of the study started in 2024 in the United States. Sites in Africa are planned to join Part 2/Phase II of the study.
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 15/08/2024
Actual trial start date 15/08/2024
Anticipated date of last follow up 18/04/2029
Actual Last follow-up date
Anticipated target sample size (number of participants) 161
Actual target sample size (number of participants)
Recruitment status Recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
NCT06546670 clinicaltrials.gov
2024 515696 35 00 EU CTIS
CITU512A12101 company identifier
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 Central randomisation by phone/fax Masking/blinding used Outcome Assessors,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group ITU512 up to 4 months ITU512 is an investigational, oral, low molecular weight (LMW) compound. It is administered orally as a capsule. 124
Control Group Placebo up to 4 months An inactive substance that looks like and is given the same way as ITU512. It is administered orally as a capsule. 37 Placebo
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Part 1 (Healthy participants) - Healthy male participants and female participants of non-childbearing potential between 18‑55 years of age - In good health as determined by the investigator's assessment of medical history, physical examination, vital signs, ECG, and laboratory tests - Participants must weigh at least 50 kg at screening and first baseline (admission) and must have a body mass index (BMI) within the range of 18.0-32.0 kg/m2 inclusive. Part 2 (Sickle Cell Disease) - Male and female participants with a diagnosis of sickle cell disease Part 1 (Healthy participants) - QTcF ≥ 450 msec (as a mean value of triplicates) - History of arrhythmias - History of significant illness which has not resolved within two (2) weeks prior to initial dosing - Women of child-bearing potential (WOCBP) Part 2 (Sickle Cell Disease) -Current use of hydroxyurea/hydroxycarbamide (HU/HC)-QTcF ≥ 450 msec (as a mean value of triplicates) -History of arrhythmias Adolescent: 13 Year-18 Year,Adult: 19 Year-44 Year,Child: 6 Year-12 Year,Middle Aged: 45 Year(s)-64 Year(s) 12 Year(s) 55 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
No 27/06/2025 Korle Bu Teaching Hospital IRB
Ethics Committee Address
Street address City Postal code Country
Korle Bu, Accra Accra 233 Ghana
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 15/07/2025 Scientific Ethics Review Unit
Ethics Committee Address
Street address City Postal code Country
Off Raila Odinga Way, Nairobi Kenya Nairobi 54840-002 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 05/07/2025 Getrudes Childrens Hospital IRB
Ethics Committee Address
Street address City Postal code Country
Muthaiga Road 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
No 20/07/2025 Scientific Ethics Review Unit
Ethics Committee Address
Street address City Postal code Country
Off Raila Odinga Way, Nairobi Kenya Nairobi 54840-002 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 15/07/2025 Joint Clinical Research Centre
Ethics Committee Address
Street address City Postal code Country
Plot 101 Upper Lubowa Estate, Off Entebbe Road Kampala 10005 Uganda
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 24/07/2024 U.S. Food and Drug Administration
Ethics Committee Address
Street address City Postal code Country
Silver Spring, MD 20993 Silver Spring MD 20993 United States of America
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 28/07/2025 Committee on Human Research Publication and Ethics
Ethics Committee Address
Street address City Postal code Country
School of Medicine and Dentistry, KNUST, Kumasi, Ashanti Region, Ghana Kumasi 233 Ghana
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 28/07/2025 Ghana Health Service Ethics Review Commission
Ethics Committee Address
Street address City Postal code Country
Adabraka Polyclinic Opposite Accra Psychiatric Hospital Cathedral Square Castle Road, Greater Accra Region Accra 233 Ghana
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Part 1A, Part 1B, Part 1C: Incidence of AEs and SAEs Up to approximately 60 days
Primary Outcome Part 1A, Part 1B , Part 1C: Dose discontinued due to AE Up to 30 days
Primary Outcome Part 2: Incidence of AEs and SAEs Up to 5 months
Primary Outcome Part 2: Dose interruptions and reductions Up to 4 months
Primary Outcome Part 2: Dose intensity Up to 4 months
Primary Outcome Part 2: HbF% evaluated from central laboratory assessments at Month 4 Month 4
Secondary Outcome Part 1A, Part 1B: Area under the plasma concentration-time curve (AUC) of ITU512 Part 1A: from pre-dose up to 144 hours post-dose on Day 1 Part 1B: from pre-dose up to 24 hours post-dose on Day 1 and Day 10
Secondary Outcome Part 1A, Part 1B: Maximum plasma concentration (Cmax) of ITU512 Part 1A: from pre-dose up to 144 hours post-dose on Day 1 Part 1B: from pre-dose up to 24 hours post-dose on Day 1 and Day 10
Secondary Outcome Part 1A, Part 1B: Time to maximum plasma concentration (Tmax) of ITU512 Part 1A: from pre-dose up to 144 hours post-dose on Day 1 Part 1B: from pre-dose up to 24 hours post-dose on Day 1 and Day 10
Secondary Outcome Part 1A, Part 1B: Renal clearance (CLr) Part 1A: from pre-dose up to 48 hours post-dose on Day 1 Part 1B: from pre-dose up to 24 hours post-dose on Day 1 and Day 10
Secondary Outcome Part 2: Plasma concentrations of ITU512 From pre-dose up to 4 or 6 hours post-dose on Day 1 at Month 1 and Month 2
Secondary Outcome Part 2: Urine concentrations of ITU512 From pre-dose up to 4 or 6 hours post-dose on Day 1 at Month 1
Secondary Outcome Part 2: Fetal hemoglobin (HbF)% Up to 4 months
Secondary Outcome Part 2: Change from baseline in total hemoglobin (Hb) Baseline, up to 4 months
Secondary Outcome Part 1A, Part 1B, Part 2: Change from baseline in Fridericia-corrected Holter QT interval (QTcF) Up to 4 months
Secondary Outcome Part 1C: Area under the plasma concentration-time curve from time 0 up to the time of the last quantifiable concentration (AUClast) of ITU512 From pre-dose up to 144 hours post-dose
Secondary Outcome Part 1C: Area under the plasma concentration-time curve from time 0 up to infinity (AUCinf) of ITU512 From pre-dose up to 144 hours post-dose
Secondary Outcome Part 1C: Maximum plasma concentration (Cmax) of ITU512 From pre-dose up to 144 hours post-dose
Secondary Outcome Part 1C: Time to maximum plasma concentration (Tmax) of ITU512 From pre-dose up to 144 hours post-dose
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Ghana Institute of Clinical genetics Korle Bu Teaching Hospital Accra 233 Ghana
International Cancer Institute Nandi Road Eldoret 30100 Kenya
Gertrude s Childrens Hospital 34 Muthaiga Road Nairobi 00100 Kenya
KEMRI Kondele Childrens Hospital Jaramogi Oginga Odinga Teaching and Referral Hospital Along Kisumu Kakamega Road Kisumu 40100 Kenya
Joint Clinical Research Centre Lubowa Estates, Off Entebbe Road Kampala 10005 Uganda
Malaria Research Center Agogo Presbyterian Hospital Agogo 233 Ghana
FUNDING SOURCES
Name of source Street address City Postal code Country
Novartis Pharmaceuticals Fabrikstrasse 2 Basel 4056 Switzerland
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Novartis Pharmaceuticals Fabrikstrasse 2 Basel 4056 Switzerland Commercial Sector/Industry
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Yvonne Dei adomakoh deiadom@yahoo.com +233243550980 Korle Bu Teaching Hospital
City Postal code Country Position/Affiliation
Accra 233 Ghana Ghana Institute of Clinical Genetics
Role Name Email Phone Street address
Public Enquiries Novartis Pharmaceuticals Novartis Pharmaceuticals novartis.email@novartis.com +41613241111 Fabrikstrasse 2
City Postal code Country Position/Affiliation
Basel 4056 Switzerland Trial Director
Role Name Email Phone Street address
Scientific Enquiries Novartis Pharmaceuticals Novartis Pharmaceuticals novartis.email@novartis.com +41613241111 Fabrikstrasse 2
City Postal code Country Position/Affiliation
Basel 4056 Switzerland Trial Director
Role Name Email Phone Street address
Principal Investigator Henry Mugerwa hmugerwa@jcrc.org.ug +256704621379 Joint Clinical Research Centre Plot 101 Lubowa Estates, Off Entebbe Road
City Postal code Country Position/Affiliation
Kampala 10005 Uganda Director
Role Name Email Phone Street address
Principal Investigator Doreen Mutua dkarimi@gerties.org +254722384218 Gertrudes Childrens Hospital, 34 Muthaiga Road
City Postal code Country Position/Affiliation
Nairobi 00100 Kenya Principal Investigator
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. Clinical Study Report,Statistical Analysis Plan,Study Protocol This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients and healthy participants who have participated in the trial in line with applicable law sand regulations.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
www.clinicalstudydatarequest.com 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
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Trial description 25/04/2025 to address reviewers comment (Under summary, please also provide a brief background about your study and not only how it was be conducted) The purpose of this global Phase I/II study is to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary food effect of ITU512 including the fetal hemoglobin (HbF)-inducing capacity of ITU512. This will be the first evaluation of the potential therapeutic effect of ITU512. The study consists of a first-in-human Phase I study (Part 1) in healthy adult participants, and a Phase II study (Part 2) in adolescent and adult patients with sickle cell disease (SCD). Part 1 will comprise of Part 1A, Part 1B, and Part 1C. Part 2 will comprise of Part 2A, Part 2B and optional Part 2C extension. Recruitment centres listed below are planned to join Part 2 of the study. Sickle cell disease (SCD) is a life-threatening genetic disorder with the global burden residing in sub-Saharan Africa. SCD is caused by a single mutation in the β globin gene resulting in the production of an abnormal form of hemoglobin. Patients with SCD are protected at birth due to high levels of fetal hemoglobin (HbF), encoded by the γ globin gene. However, symptoms of SCD arise when expression of HbF declines, typically in the first year of life. ITU512, an orally available investigational compound, has been proven in pre-clinical studies to induce HbF expression, a therapeutic strategy which has been associated with improvement in clinical outcomes and increased survival in SCD patients. The purpose of this global Phase I/II study is to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary food effect of ITU512 including the fetal hemoglobin (HbF)-inducing capacity of ITU512. This will be the first evaluation of the potential therapeutic effect of ITU512. The study consists of a first-in-human Phase I study (Part 1) in healthy adult participants, and a Phase II study (Part 2) in adolescent and adult patients with sickle cell disease (SCD). Part 1 will comprise of Part 1A, Part 1B, and Part 1C. Part 2 will comprise of Part 2A, Part 2B and optional Part 2C extension. Recruitment centres listed below are planned to join Part 2 of the study.
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Trial description 25/04/2025 to address comment by trial reviewer Sickle cell disease (SCD) is a life-threatening genetic disorder with the global burden residing in sub-Saharan Africa. SCD is caused by a single mutation in the β globin gene resulting in the production of an abnormal form of hemoglobin. Patients with SCD are protected at birth due to high levels of fetal hemoglobin (HbF), encoded by the γ globin gene. However, symptoms of SCD arise when expression of HbF declines, typically in the first year of life. ITU512, an orally available investigational compound, has been proven in pre-clinical studies to induce HbF expression, a therapeutic strategy which has been associated with improvement in clinical outcomes and increased survival in SCD patients. The purpose of this global Phase I/II study is to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary food effect of ITU512 including the fetal hemoglobin (HbF)-inducing capacity of ITU512. This will be the first evaluation of the potential therapeutic effect of ITU512. The study consists of a first-in-human Phase I study (Part 1) in healthy adult participants, and a Phase II study (Part 2) in adolescent and adult patients with sickle cell disease (SCD). Part 1 will comprise of Part 1A, Part 1B, and Part 1C. Part 2 will comprise of Part 2A, Part 2B and optional Part 2C extension. Recruitment centres listed below are planned to join Part 2 of the study. Sickle cell disease (SCD) is a life-threatening genetic disorder with the global burden residing in sub-Saharan Africa. SCD is caused by a single mutation in the β globin gene resulting in the production of an abnormal form of hemoglobin. Patients with SCD are protected at birth due to high levels of fetal hemoglobin (HbF), encoded by the γ globin gene. However, symptoms of SCD arise when expression of HbF declines, typically in the first year of life. ITU512, an orally available investigational compound, has been proven in pre-clinical studies to induce HbF expression, a therapeutic strategy which has been associated with improvement in clinical outcomes and increased survival in SCD patients. The purpose of this global Phase I/II study is to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary food effect of ITU512 including the fetal hemoglobin (HbF)-inducing capacity of ITU512. This will be the first evaluation of the potential therapeutic effect of ITU512. The study consists of a first-in-human Phase I study (Part 1) in healthy adult participants, and a Phase II study (Part 2) in adolescent and adult patients with sickle cell disease (SCD). Part 1 will comprise of Part 1A, Part 1B, and Part 1C. Part 2 will comprise of Part 2A, Part 2B and optional Part 2C extension. Part 1/Phase I of the study started in 2024 in the United States. Sites in Africa are planned to join Part 2/Phase II of the study in 2025
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Trial description 25/04/2025 to address comment by trial reviewer Sickle cell disease (SCD) is a life-threatening genetic disorder with the global burden residing in sub-Saharan Africa. SCD is caused by a single mutation in the β globin gene resulting in the production of an abnormal form of hemoglobin. Patients with SCD are protected at birth due to high levels of fetal hemoglobin (HbF), encoded by the γ globin gene. However, symptoms of SCD arise when expression of HbF declines, typically in the first year of life. ITU512, an orally available investigational compound, has been proven in pre-clinical studies to induce HbF expression, a therapeutic strategy which has been associated with improvement in clinical outcomes and increased survival in SCD patients. The purpose of this global Phase I/II study is to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary food effect of ITU512 including the fetal hemoglobin (HbF)-inducing capacity of ITU512. This will be the first evaluation of the potential therapeutic effect of ITU512. The study consists of a first-in-human Phase I study (Part 1) in healthy adult participants, and a Phase II study (Part 2) in adolescent and adult patients with sickle cell disease (SCD). Part 1 will comprise of Part 1A, Part 1B, and Part 1C. Part 2 will comprise of Part 2A, Part 2B and optional Part 2C extension. Part 1/Phase I of the study started in 2024 in the United States. Sites in Africa are planned to join Part 2/Phase II of the study in 2025 Sickle cell disease (SCD) is a life-threatening genetic disorder with the global burden residing in sub-Saharan Africa. SCD is caused by a single mutation in the β globin gene resulting in the production of an abnormal form of hemoglobin. Patients with SCD are protected at birth due to high levels of fetal hemoglobin (HbF), encoded by the γ globin gene. However, symptoms of SCD arise when expression of HbF declines, typically in the first year of life. ITU512, an orally available investigational compound, has been proven in pre-clinical studies to induce HbF expression, a therapeutic strategy which has been associated with improvement in clinical outcomes and increased survival in SCD patients. The purpose of this global Phase I/II study is to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary food effect of ITU512 including the fetal hemoglobin (HbF)-inducing capacity of ITU512. This will be the first evaluation of the potential therapeutic effect of ITU512. The study consists of a first-in-human Phase I study (Part 1) in healthy adult participants, and a Phase II study (Part 2) in adolescent and adult patients with sickle cell disease (SCD). Part 1 will comprise of Part 1A, Part 1B, and Part 1C. Part 2 will comprise of Part 2A, Part 2B and optional Part 2C extension. Part 1/Phase I of the study started in 2024 in the United States. Sites in Africa are planned to join Part 2/Phase II of the study in 2025.
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Trial description 15/05/2025 removed reference to 2025. Sickle cell disease (SCD) is a life-threatening genetic disorder with the global burden residing in sub-Saharan Africa. SCD is caused by a single mutation in the β globin gene resulting in the production of an abnormal form of hemoglobin. Patients with SCD are protected at birth due to high levels of fetal hemoglobin (HbF), encoded by the γ globin gene. However, symptoms of SCD arise when expression of HbF declines, typically in the first year of life. ITU512, an orally available investigational compound, has been proven in pre-clinical studies to induce HbF expression, a therapeutic strategy which has been associated with improvement in clinical outcomes and increased survival in SCD patients. The purpose of this global Phase I/II study is to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary food effect of ITU512 including the fetal hemoglobin (HbF)-inducing capacity of ITU512. This will be the first evaluation of the potential therapeutic effect of ITU512. The study consists of a first-in-human Phase I study (Part 1) in healthy adult participants, and a Phase II study (Part 2) in adolescent and adult patients with sickle cell disease (SCD). Part 1 will comprise of Part 1A, Part 1B, and Part 1C. Part 2 will comprise of Part 2A, Part 2B and optional Part 2C extension. Part 1/Phase I of the study started in 2024 in the United States. Sites in Africa are planned to join Part 2/Phase II of the study in 2025. Sickle cell disease (SCD) is a life-threatening genetic disorder with the global burden residing in sub-Saharan Africa. SCD is caused by a single mutation in the β globin gene resulting in the production of an abnormal form of hemoglobin. Patients with SCD are protected at birth due to high levels of fetal hemoglobin (HbF), encoded by the γ globin gene. However, symptoms of SCD arise when expression of HbF declines, typically in the first year of life. ITU512, an orally available investigational compound, has been proven in pre-clinical studies to induce HbF expression, a therapeutic strategy which has been associated with improvement in clinical outcomes and increased survival in SCD patients. The purpose of this global Phase I/II study is to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary food effect of ITU512 including the fetal hemoglobin (HbF)-inducing capacity of ITU512. This will be the first evaluation of the potential therapeutic effect of ITU512. The study consists of a first-in-human Phase I study (Part 1) in healthy adult participants, and a Phase II study (Part 2) in adolescent and adult patients with sickle cell disease (SCD). Part 1 will comprise of Part 1A, Part 1B, and Part 1C. Part 2 will comprise of Part 2A, Part 2B and optional Part 2C extension. Part 1/Phase I of the study started in 2024 in the United States. Sites in Africa are planned to join Part 2/Phase II of the study.
Section Name Field Name Date Reason Old Value Updated Value
Eligibility Inclusion criteria 25/04/2025 to address comment by trial reviewer Part 1 (Healthy participants)- Healthy male participants and female participants of non-childbearing potential between 18‑55 years of age- In good health as determined by the investigator's assessment of medical history, physical examination, vital signs, ECG, and laboratory tests- Participants must weigh at least 50 kg at screening and first baseline (admission) and must have a body mass index (BMI) within the range of 18.0-32.0 kg/m2 inclusive. Part 2 (Sickle Cell Disease)- Male and female participants with a diagnosis of sickle cell disease Part 1 (Healthy participants) - Healthy male participants and female participants of non-childbearing potential between 18‑55 years of age - In good health as determined by the investigator's assessment of medical history, physical examination, vital signs, ECG, and laboratory tests - Participants must weigh at least 50 kg at screening and first baseline (admission) and must have a body mass index (BMI) within the range of 18.0-32.0 kg/m2 inclusive. Part 2 (Sickle Cell Disease) - Male and female participants with a diagnosis of sickle cell disease
Section Name Field Name Date Reason Old Value Updated Value
Eligibility Exclusion criteria 25/04/2025 to address comment by trial reviewer Part 1 (Healthy participants)- QTcF ≥ 450 msec (as a mean value of triplicates) - History of arrhythmias- History of significant illness which has not resolved within two (2) weeks prior to initial dosing- Women of child-bearing potential (WOCBP)Part 2 (Sickle Cell Disease)-Current use of hydroxyurea/hydroxycarbamide (HU/HC)-QTcF ≥ 450 msec (as a mean value of triplicates) -History of arrhythmias Part 1 (Healthy participants) - QTcF ≥ 450 msec (as a mean value of triplicates) - History of arrhythmias - History of significant illness which has not resolved within two (2) weeks prior to initial dosing - Women of child-bearing potential (WOCBP) Part 2 (Sickle Cell Disease) -Current use of hydroxyurea/hydroxycarbamide (HU/HC)-QTcF ≥ 450 msec (as a mean value of triplicates) -History of arrhythmias
Section Name Field Name Date Reason Old Value Updated Value
Intervention Intervention List 25/04/2025 to address comment by trial reviewer Experimental Group, ITU512, , up to 4 months, ITU512 is an investigational, oral, low molecular weight (LMW) compound., 124, Experimental Group, ITU512, , up to 4 months, ITU512 is an investigational, oral, low molecular weight (LMW) compound. It is administered orally as a capsule., 124,
Section Name Field Name Date Reason Old Value Updated Value
Intervention Intervention List 25/04/2025 to address comment by trial reviewer Control Group, Placebo, , up to 4 months, An inactive substance that looks like and is given the same way as ITU512., 37, Placebo Control Group, Placebo, , up to 4 months, An inactive substance that looks like and is given the same way as ITU512. It is administered orally as a capsule., 37, Placebo
Section Name Field Name Date Reason Old Value Updated Value
Recruitment Centre RecruitmentCentre List 14/05/2025 Recruitment centre added Malaria Research Center, Agogo Presbyterian Hospital, Agogo, 233, Ghana
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 21/07/2025 EC submission date corrected FALSE, Korle Bu Teaching Hospital IRB, Korle Bu, Accra, Accra, 233, Ghana, 19 May 2025, , +2333026677596730, info@kbth.gov.gh, FALSE, Korle Bu Teaching Hospital IRB, Korle Bu, Accra, Accra, 233, Ghana, 27 Jun 2025, , +2333026677596730, info@kbth.gov.gh,
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 21/07/2025 EC submission date corrected FALSE, Scientific Ethics Review Unit, Off Raila Odinga Way, Nairobi Kenya, Nairobi, 54840-002, Kenya, 15 May 2025, , +254717719477, seru@kemri.org, FALSE, Scientific Ethics Review Unit, Off Raila Odinga Way, Nairobi Kenya, Nairobi, 54840-002, Kenya, 15 Jul 2025, , +254717719477, seru@kemri.org,
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 21/07/2025 EC submission date corrected FALSE, Getrudes Childrens Hospital IRB, Muthaiga Road, Nairobi, 42325-001, Kenya, 15 May 2025, , +254207206000, ethics@gerties.org, FALSE, Getrudes Childrens Hospital IRB, Muthaiga Road, Nairobi, 42325-001, Kenya, 05 Jul 2025, , +254207206000, ethics@gerties.org,
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 21/07/2025 EC submission date corrected FALSE, Scientific Ethics Review Unit, Off Raila Odinga Way, Nairobi Kenya, Nairobi, 54840-002, Kenya, 15 May 2025, , +254717719477, seru@kemri.org, FALSE, Scientific Ethics Review Unit, Off Raila Odinga Way, Nairobi Kenya, Nairobi, 54840-002, Kenya, 20 Jul 2025, , +254717719477, seru@kemri.org,
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 21/07/2025 EC submission date corrected FALSE, Joint Clinical Research Centre, Plot 101 Upper Lubowa Estate, Off Entebbe Road, Kampala, 10005, Uganda, 30 May 2025, , +256417723000, jcrc@jcrc.org.ug, FALSE, Joint Clinical Research Centre, Plot 101 Upper Lubowa Estate, Off Entebbe Road, Kampala, 10005, Uganda, 15 Jul 2025, , +256417723000, jcrc@jcrc.org.ug,
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 15/05/2025 FDA approval added TRUE, U.S. Food and Drug Administration, Silver Spring, MD 20993, Silver Spring, MD 20993, United States of America, , 24 Jul 2024, +13017967775, May.Zuwannin@fda.hhs.gov,
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 21/07/2025 EC submission added FALSE, Committee on Human Research Publication and Ethics, School of Medicine and Dentistry, KNUST, Kumasi, Ashanti Region, Ghana, Kumasi, 233, Ghana, 28 Jul 2025, , +233322063248, chrpe.knust.kath@gmail.com,
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 21/07/2025 EC submission added FALSE, Ghana Health Service Ethics Review Commission, Adabraka Polyclinic Opposite Accra Psychiatric Hospital Cathedral Square Castle Road, Greater Accra Region, Accra, 233, Ghana, 28 Jul 2025, , +233504698534, info@rdd-ghs.com,
Section Name Field Name Date Reason Old Value Updated Value
Contact People Contacs List 25/04/2025 to address comment by trial reviewer - contact added Principal Investigator, Henry, Mugerwa, Dr., hmugerwa@jcrc.org.ug, , +256417723000, Joint Clinical Research Centre, Lubowa Estates, Off Entebbe Road, Kampala, 10005, Uganda, Director
Section Name Field Name Date Reason Old Value Updated Value
Contact People Contacs List 14/05/2025 to address comment by trial reviewer - contact added Principal Investigator, Henry, Mugerwa, Dr., hmugerwa@jcrc.org.ug, , +256417723000, Joint Clinical Research Centre, Lubowa Estates, Off Entebbe Road, Kampala, 10005, Uganda, Director Principal Investigator, Henry, Mugerwa, Dr., hmugerwa@jcrc.org.ug, , +256704621379, Joint Clinical Research Centre Plot 101 Lubowa Estates, Off Entebbe Road, Kampala, 10005, Uganda, Director
Section Name Field Name Date Reason Old Value Updated Value
Contact People Contacs List 14/05/2025 to address comment by trial reviewer - contact added Principal Investigator, Doreen, Mutua, Dr., dkarimi@gerties.org, , +254722384218, Gertrudes Childrens Hospital, 34 Muthaiga Road , Nairob, 00100, Kenya, Principal Investigator
Section Name Field Name Date Reason Old Value Updated Value
Contact People Contacs List 14/05/2025 to address comment by trial reviewer - contact added Principal Investigator, Doreen, Mutua, Dr., dkarimi@gerties.org, , +254722384218, Gertrudes Childrens Hospital, 34 Muthaiga Road , Nairob, 00100, Kenya, Principal Investigator Principal Investigator, Doreen, Mutua, Dr., dkarimi@gerties.org, , +254722384218, Gertrudes Childrens Hospital, 34 Muthaiga Road , Nairobi, 00100, Kenya, Principal Investigator