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.: PACTR202506834698530 Date of Approval: 20/06/2025
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Novel phytopharmaceutical alpha linolenic acid 18n:3 nanoformulation for symptomatic treatment of acute and chronic pain in homozygous HbSS sickle cell disease patients
Official scientific title Innovative, standardized linseed oil extract based alpha linolenic acid 18n:3 formulation targeted at treating acute and chronic painful complications in sickle cell crisis
Brief summary describing the background and objectives of the trial Existing reference treatment of sickle cell disease crisis consists of hydroxyurea, a myelosuppressive agent, linked to severe side effects, e.g., neutropenia, nausea, vomiting, anorexia, elevation of hepatic enzymes, infertility and blood transfusions, alone or in combination with hydroxyurea and gene therapy. Hence, there is a medical need for a cost-effective treatment alternative, broadly available in the sickle cell disease patient community offering a cheap, sustainable alternative void of side effects. The objectives of the present randomized, double-blinded placebo-controlled trial are to assess the tolerability and optimal dose of (Phase 1a First-in-Human [FIH] trial selection in healthy volunteers) and to determine the optimal dose to be administered in sickle cell disease patients with or without blood transfusions during a Phase 1b/2a Proof-of-Concept [POC] trial section in comparison with standard reference treatment (hydroxyurea, folic acid, analgesics and blood transfusions).
Type of trial CCT
Acronym (If the trial has an acronym then please provide) SOULAGE
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 01/09/2025
Actual trial start date
Anticipated date of last follow up 01/09/2026
Actual Last follow-up date
Anticipated target sample size (number of participants) 64
Actual target sample size (number of participants)
Recruitment status Not yet recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
SEN2535 National Senegal Ethics Committee for Research in Health CNERS
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 Simple randomization using a randomization table created by a computer software program Numbered containers Masking/blinding used Care giver/Provider,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group ALADRE SOULAGE 1 Part 1: 137,5 mg QD (once daily) Part 2: 275 mg QD (once daily) Part 3: 275 mg BID (twice daily) Part 4: 550 mg BID (twice daily) 2 weeks ALADRE sachets containing 137,5 mg, 275 mg and 550 mg of alpha linolenic acid 18n:3 formulation as emulsion and the following excipients: gum arabic Ph.Eur., gelatin Ph.Eur., Lipoid S100 phosphatidylcholin, Tween 80 Ph.Eur. and SPAN 80 16
Control Group Placebo SOULAGE 1 Part 1: Corn Oil 1 g QD (once daily) Part 2: Corn Oil 1 g QD (once daily) Part 3: Corn Oil 1 g BID (twice daily) Part 4: Corn Oil 1 g BID (twice daily) 2 weeks Placebo sachets containing 1 g of native, refined, extracted, standardized corn oil Ph. Eur. 12.1 without excipients 12 Placebo
Experimental Group ALADRE SOULAGE 2 Part 1: ALADRE (alpha linolenic acid) 137,5 mg BID (twice daily) + hydroxyurea 15 mg/kg/day + folic acid 2,5 mg/day oral dosing Part 2: ALADRE (alpha linolenic acid) 275 mg BID (twice daily) + hydroxyurea 15 mg/kg/day + folic acid 2,5 mg/day oral dosing 3 weeks Sachets containing 137,5 mg or 275 mg of alpha linolenic acid 18n:3 and the following excipients: gum arabic Ph.Eur., gelatin Ph.Eur., Lipoid S100 phosphatidylcholin, Tween 80 Ph.Eur. and SPAN 80 12
Control Group Reference Treatment SOULAGE 2 15 mg/kg/day of hydroxyurea and 2,5 mg/day of folic acid 3 weeks capsules of reference treatment (active-treatment control group as placebo) of hydroxyurea and folic acid corresponding to doses mentioned above 6 Active-Treatment of Control Group
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Please note that these are key inclusion criteria for all participants. Additional cohort-specific inclusion criteria may apply. SOULAGE 1 Study Part: 1. Participant (healthy volunteer) is able to understand and provide informed consent prior to the conduct of any protocol-specific screeing procedures. 2. Participant is able to complete all study assessments and procedures. 3. Participant is able to swallow tablets and emulsion as contained in sachets. 4. Participant has a body weight at inclusion visit of at least 40 kg. 5. Participant has undergone a normal medical examination during screening visit consisting of clinical examination, blood level analyses, medical history and electrocardiogramme (12 derivation ECG). SOULAGE 2 Study Part A: Confirmed Sickle Cell Disease With Blood Transfusions 1. Participant (sickle cell disease patient with blood transfusions) is able to understand and provide informed consent prior to the conduct of any protocol-specific screeing procedures. 2. Participant is able to complete all study assessments and procedures. 3. Participant is able to swallow tablets and emulsion as contained in sachets. 4. Participant has a body weight at inclusion visit of at least 40 kg. 5. Participant has undergone medical examination during screening visit consisting of clinical examination, blood level analyses, medical history and electrocardiogramme (12 derivation ECG). 6. At least one blood transfusion/month during 24 months for secondary prevention of cerebrovascular SOULAGE 2 Study Part B: Confirmed Sickle Cell Disease Without Blood Transfusions 1. Participant (sickle cell disease patient without blood transfusions) is able to understand and provide informed consent prior to the conduct of any protocol-specific screeing procedures. 2. Participant is able to complete all study assessments and procedures. 3. Participant is able to swallow tablets and emulsion as contained in sachets. 4. and 5. as in Part A above Please note that these are key exclusion criteria for all participants. Additional cohort-specific exclusion criteria may apply. The following exclusion citeria apply to all cohorts of SOULAGE 1 and SOULAGE 2 Study Parts A and B: 1. Breast-feeding or pregnancy in female participants 2. Hepatic dysfunction or insufficiency as defined by: - AST and/or ALT values exceeding at least 4 times the upper limits of normal, respectively - free, non conjugated bilirubin exceeding at least 3 times the upper limit of normal - liver cirrhosis as confirmed by anamnesis 3. HIV positivity 4. Acute hepatitis B or C infection 5. Chronic renal insufficiency grade 3, 4 or 5 as defined by GFR < 60 ml/min 6. Malignant tumor as confirmed by prior chemotherapy or radiotherapy during the 24 months preceding the intake of the first dose of the study product 7. Unstable cardiac and/or pulmonary disease as evidenced by anamnesis during the 6 months prior to the participant providing written informed consent and comprising the follwoing disease conditions: - unstable angina, myocardial infarction or invasive coronary treatment - heart failure hospital treatment - cardiac arrhythmia - symptomatic arterial pulmonary hypertension 8. Participant havin received another investigational drug drug within 30 days or 5 half-lives, whichever is longer, prior to taking the first dose of the study product 9. Participant having undergone major surgery within 6 months prior to taking the first study product Adolescent: 13 Year-18 Year,Adult: 19 Year-44 Year,Aged: 65+ Year(s),Middle Aged: 45 Year(s)-64 Year(s) 12 Year(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
No 30/06/2025 CNERS Senegal
Ethics Committee Address
Street address City Postal code Country
Rue Aime Cesaire - Fann Residence Dakar 10700 Senegal
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome SOULAGE 1, SOULAGE 2 Study Part A and SOULAGE 2 Study Part B - Incidence, frequency and severity of adverse events and serious adverse events - Vital signs including blood pressure, herat and respiratory rates, oral temperature, body weight, bedside 12-lead ECG monitoring heart rate, PR and RR intervals, respectively, QRS duration, QT and QTcF intervals. Physical medical examination. Concomitant medication usage. Clinical chemistry including blood chemistry, urinalysis. Hematology analysis including coagulation parameters. Immunology analysis including inflammatory marker proteins, i.e., hsCRP and others. Plasma pharmacokinetic parameter analysis for study drug including but not limited to Cmax, Tmax, AUC 0-24, AUC 0-last, t1/2, CL/F, Vd/F, dose proportionality following single and multiple dose administration. In addition, as regards SOULAGE Study Parts A and B - increase of hemoglobinemia Hb of at least 1 g/100 ml vs. baseline value 12 weeks following study drug compared active control reference treatment. Primary and secondary outcomes assessed at baseline and at all subsequents visits until the completion of the study
Secondary Outcome SOULAGE 2 Study Parts A and B - Change from baseline in percentage of sickle cells and HbF hemoglobinemia, F reticulocytes, F cells and in pharmacokinetic parameters, e.g., Cmax, Tmax, AUC 0-24 and AUC 0 - last - Percentage ncrease of Hb hemoglobinemia of at least 1,0 g/100 ml vs. baseline 12, 24 and 48 weeks following the intake of the last dose of study drug - Serum ferritins changes vs. baseline 12, 24 and 48 weeks follwoing last intake of study drug - Change from baseline in plasma thrombocyte concentration and vWF, P-selectin, VCAM-1, ICAM-1 and MCP-1 12 weeks following last intake of study drug - Change from baseline in hsCRP serum concentration at 12 weeks and changes in activation marker levels of pro-oxydant inflammatory mediators measured in peripheral blood mononuclear cells PBMCs following intake of the last study dose, respectively. In addition to the above, SOULAGE Study Part B determines the percentage of participants, i.e., patients, with sickle cell disease receiving blood transfusions in whom a reduction of at least 20 percent vs. active control treatment, e.g., consisting of standard reference treatment with hydroxyurea and folic acid and analgesics, of blood transfusions of erythrocyte concentrates has been determined at 12 weeks following intake of the last dose of study drug - Reduction of the number of blood transfusion erythrocyte concentrates 12, 24 and 48 weeks, respectively following the last intake of the study drug. Primary and secondary outcomes assessed at baseline and at all subsequent visits until study completion
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Centre National de Transfusion Sanguine CNTS Avenue Cheikh Anta Diop Dakar Senegal
FUNDING SOURCES
Name of source Street address City Postal code Country
University of Saarland Campus C4 1 Saarbruecken Germany
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Saarland University Campus C4 1 Saarbruecken 66123 Germany University
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Scientific Enquiries Paul Kerth paul.kerth@preventor.de +49615787947 Gernsheimer Strasse 46
City Postal code Country Position/Affiliation
Pfungstadt 64319 Germany Associated Principal Investigator
Role Name Email Phone Street address
Principal Investigator Modou Oumy Kane kanebamba@yahoo.fr +221776551234 Avenue Cheikh Anta Diop
City Postal code Country Position/Affiliation
Dakar Senegal Principal Investigator
Role Name Email Phone Street address
Public Enquiries Saliou DIOP saliou.diop@ucad.edu.sn +221338698661 Avenue Cheikh Anta Diop
City Postal code Country Position/Affiliation
Dakar Senegal Associated Principal Investigator
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Anonymized individual participant data that underlies the results reported in the clinical study report (CSR) will be shared. This includes baseline characteristics, outcome measures and adverse events data. No information that would allow to identify data from individual study participants will be included. Clinical Study Report The data will be made available no later than 12 months after the study completion date. Dissemination of individual patient data will follow all applicable local regulations for data reporting requirements. The propsed use will and shall be scientifically and and ethically appropriate. The requesting party must sign a data use agreement, agree to use the data for the approved purpose and assure data confidentiality and security of data storage.
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
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Trial description 20/06/2025 PACTR Admin Existing reference treatment of sickle cell disease crisis consists of hydroxyurea, a myelosuppressive agent, linked to severe side effects, e.g., neutropenia, nausea, vomiting, anorexia, elevation of hepatic enzymes, infertility and blood transfusions, alone or in combination with hydroxyurea and gene therapy. Hence, there is a medical need for a cost-effective treatment alternative, broadly available in the sickle cell disease patient community offering a cheap, sustainable alternative void of side effects. The objectives of the present tandomized, double-blinded placebo-controlled trial are to assess the tolerability and optimal dose of (Phase 1a First-in-Human [FIH] trial selection in healthy volunteers) and to determine the optimal dose to be administered in sickle cell disease patients with or without blood transfusions during a Phase 1b/2a Proof-of-Concept [POC] trial section in comparison with standard reference treatment (hydroxyurea, folic acid, analgesics and blood transfusions). Existing reference treatment of sickle cell disease crisis consists of hydroxyurea, a myelosuppressive agent, linked to severe side effects, e.g., neutropenia, nausea, vomiting, anorexia, elevation of hepatic enzymes, infertility and blood transfusions, alone or in combination with hydroxyurea and gene therapy. Hence, there is a medical need for a cost-effective treatment alternative, broadly available in the sickle cell disease patient community offering a cheap, sustainable alternative void of side effects. The objectives of the present randomized, double-blinded placebo-controlled trial are to assess the tolerability and optimal dose of (Phase 1a First-in-Human [FIH] trial selection in healthy volunteers) and to determine the optimal dose to be administered in sickle cell disease patients with or without blood transfusions during a Phase 1b/2a Proof-of-Concept [POC] trial section in comparison with standard reference treatment (hydroxyurea, folic acid, analgesics and blood transfusions).
Section Name Field Name Date Reason Old Value Updated Value
Eligibility Age group 20/06/2025 PACTR Admin Adolescent: 13 Year-18 Year, Adult: 19 Year-44 Year, Middle Aged: 45 Year(s)-64 Year(s) Adolescent: 13 Year-18 Year, Adult: 19 Year-44 Year, Middle Aged: 45 Year(s)-64 Year(s), Aged: 65+ Year(s)