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.: PACTR202103526168929 Date of Registration: 26/03/2021
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Multicentre randomized double-blind placebo-controlled study to evaluate the effect on albuminuria of 6months treatment with hydroxycarbamide (Siklos®) or a placebo in adults with sickle cell disease:SIKAMIC (SIklos on Kidney function and AlbuMInuria Clinical trial)
Official scientific title Multicentre randomized double-blind placebo-controlled study to evaluate the effect on albuminuria of 6months treatment with hydroxycarbamide (Siklos®) or a placebo in adults with sickle cell disease:SIKAMIC (SIklos on Kidney function and AlbuMInuria Clinical trial)
Brief summary describing the background and objectives of the trial This is a phase IIb, international (France and Africa), multicentre, double-blind, randomised, placebo-controlled study to determine the effect of hydroxycarbamide on albuminuria after 6 months of treatment in SCD adult patients. A 6 months study will allow to better document the natural history of the SCAN and to assess the response to Siklos® in adult patients with HbSS or HbSβ0 SCD and ACR between 3 to 100 mg/mmol.The patients will be recruited in France and in Africa. After having given written informed consent (ICF), they will be examined to determine their eligibility according to inclusion/exclusion criteria. The eligible patients will be randomised to receive in a 1:1 ratio: *Hydroxycarbamide (Siklos®) (hydroxycarbamide group) * Placebo (placebo group). Randomization will be stratified according to ACR baseline value: *]3-30 mg/mmol] microalbuminuria *or ]30-100 mg/mmol[ macroalbuminuria. Treatment will be administered for 6 consecutive months. Patients qualified as ‘responders’ after 6 months of treatment will be offered to continue the study treatment and their follow-up will be extended to 6 additional months.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) SIKAMIC
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 01/05/2021
Actual trial start date
Anticipated date of last follow up 28/06/2025
Actual Last follow-up date
Anticipated target sample size (number of participants) 120
Actual target sample size (number of participants)
Recruitment status Not yet recruiting
Publication URL 2018-002899-41
Secondary Ids Issuing authority/Trial register
NCT03806452 Clinicaltrials.gouv: NCT03806452
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 Simple randomization using a randomization table created by a computer software program Central randomisation by phone/fax Masking/blinding used Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Hydroxycarbamide 15mg/kg daily 6 to 12 months . The treatment will be administered for 6 consecutive months. In case of consent withdrawal, unacceptable toxicity or non-compliance to the protocol, the study treatment will be discontinued. Only patients qualified as responders after 6 months of treatment will be offered to continue to receive the study treatment andtheir follow-upwill be extended to6 additional months. Siklos® 100 mg: off-white oblong-shaped, film-coated tablet with half-scoring on both sides. Siklos® 1000 mg: off-white, capsule-shaped, film-coated tablet with triple scoring on both sides. 60
Control Group Placebo 15mg/kg daily 6 months placebo tablets formulated to be identical in appearance to Siklos® 60 Placebo
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
The inclusion criteria are to be verified at the screening and inclusion visits (V1and V2). Patients must meet ALL the following inclusion criteria to participate in the study: 1.Signed and datedInformed Consent Form(ICF)by a legally competent patient. 2.Patients above 18years. 3.Patients with HbSS or HbSβ0 SCD. 4.Patients with a value of albuminuria, assessed by ACR,over 3 mg/mmol and inferior to 100 mg/mmol confirmed by 3 positive urine samples taken one day apart. 5.Female patients of childbearing or postmenopausal female with last period < 12 months before screening agreeing to use a highly effective form of contraception (oral, injected or implanted hormonal contraception, intrauterine device, diaphragm, condom) during the trialand for 3 months after hydroxycarbamide discontinuation. 6.Male patients with partners of childbearing potential agreeing to use aneffective contraceptionduring the studyand for 3months after hydroxycarbamide discontinuation. Men with pregnant or lactating women should be advised to use barrier method contraception (condom) to prevent the foetus or neonate from exposure to hydroxycarbamide. 7.Patients who are covered by insurance scheme accordingto local regulatory requirements The exclusioncriteria are to be verified at the screening and inclusion visits (V1and V2). Patients meeting ATLEAST one of the following exclusion criteria must not be enrolled in the study: 1.Patients who had severe VOC requiring hospitalisation or ACS within the last 4 weeks preceding screening visit. 2.Patients treated with hydroxycarbamide for any reason within the previous 6months. 3.Patients who have had chronic blood transfusion or transfusion in the last 3months. 4.Patients without any semen cryopreservation performed except vasectomised patients. 5.Patients with a history of hypertension (systolic blood pressure ≥140 or diastolic blood pressure ≥90mmHg)treated with antihypertensive agent belonging to pharmacological class RAS inhibitor. 6.Patients who have symptoms suggestive of urinary tract infection or patients with gross haematuria. 7.Patients with a concomitant primary kidney disease. 8.Patients with any systemic condition that could result in a glomerulopathy not related to SCD (e.g.diabetes mellitus, active hepatitis B or C infections, systemic lupus erythematosus, inflammatory arthropathies). 9.Patient with a stage 3, 4 or 5 chronic kidney disease (eGFR<60 mL/min per 1.73m2). 10.Patients with eGFR ≥ 140 ml/min/1,73m² (due to the lack of information regarding the magnitude, direction and significance of the trends in eGFR evolution that couldbe expected in this population). 11.Patients requiring long-term treatment with drugs potentially nephrotoxic (see non-exhaustive list). 12.Patients requiring ACEinhibitors or ARBs within the 3months before inclusionregardless of the indication. 13.Patients requiring long-term treatment with non-steroidalanti-inflammatory drugs. 14.Patients who have treatment which can modify the kidney function (see non-exhaustive list) in the last 3 months. 15.Patients known to be infected with HIV. 16.Female patients who are pregnant or lactating. 17.Unreliable patients including non-compl 80 and over: 80+ Year,Adult: 18 Year(s)-44 Year(s),Aged: 65 Year(s)-79 Year(s),Middle Aged: 45 Year(s)-64 Year(s) 18 Year(s) 80 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 16/11/2020 National Ethics Committee for Health Research
Ethics Committee Address
Street address City Postal code Country
Freedom 6 Extension Dakar 00221 Senegal
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 17/11/2020 NATIONAL ETHICS COMMITTEE FOR HEALTH AND LIFE SCIENCES
Ethics Committee Address
Street address City Postal code Country
13 Koulouba BAMAKO 223 Mali
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 10/02/2021 National Committee of Ethics of Life Sciences and Health
Ethics Committee Address
Street address City Postal code Country
Institut Pasteur, Cite de Cocody Bouake 00225 Cote Divoire
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome The primary objective of this trial is to demonstrate the effect of 6-month treatment with hydroxycarbamide (Siklos®) against placebo in achieving at least a 30% decrease of the albuminuria (albumin to creatinine ratio; ACR) baseline value in adult sickle cell patients. 6 months
Secondary Outcome *To compare the estimated GFR (eGFR) according to CKD-EPI formula between hydroxycarbamide (Siklos®) and placebo groupat 6months. *To compare the proportion of patients in hydroxycarbamide versus placebo group with an improvement in the albmuminuria stage, i.e. a shift from grade A3 to grade A2 albuminuria (macro-to microalbuminuria), from grade A2 to grade A1 albuminuria (micro-to normoalbuminuria) or from grade A3 to grade A1 albuminuria (macro-tonormoalbuminuria), according to the KDIGO staging system at 6 months. *To compare the proportion of patients in hydroxycarbamide versus placebo group with a renal disease progression supported by an increase in albuminuria at 6 months, as compared to baseline. *To identify some clinical and biological markers potentially associated with response to treatment. *To describe the evolution of ACR from inclusion to month 6. *To describe the evolution of eGFR from inclusion to month 6. *To describe the evolution of ACR of responder patients from inclusion to month 12. *To describe the evolution of eGFR of responder patients from inclusion to month 12. *To evaluate the safety of hydroxycarbamide throughout the entire study period. *To evaluate the impact of the study treatment on SCD-related eventsthroughout the entire study period. 6 months
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Centre National de Transfusion sanguine Avenue Cheikh Anta Diop Fann Dakar BP 5002 Senegal
Centre de Recherche et de lutte contre la drepanocytose de Bamako Bamako Commune III, Point G Bamako 03 BP 186 Mali
Centre hospitalier universitaire 01 Bouake 01BP1174 Cote Divoire
FUNDING SOURCES
Name of source Street address City Postal code Country
ADDMEDICA S.A.S. 37 Caumartin street Paris 75009 France
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor ADDMEDICA S.A.S. 37 Caumartin street Paris 75009 France Commercial Sector/Industry
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Scientific Enquiries Corinne DUGUET corinne.duguet@addmedica.com 00330172690186 37 Caumartin street
City Postal code Country Position/Affiliation
Paris 75009 France Sponsor Medical Director
Role Name Email Phone Street address
Public Enquiries Issatou Bella Diallo issatou.diallo@mct-cro.com 0022587008200 Ivory Coast
City Postal code Country Position/Affiliation
Abidjan 00225 Cote Divoire Regional Manager
Role Name Email Phone Street address
Principal Investigator Aldiouma Guido aldguindo@icermali.org 0022366786253 03 BP 186 Bamako Commune III, Point G,
City Postal code Country Position/Affiliation
Bamako 00223 Mali Principal Investigator Mali
Role Name Email Phone Street address
Principal Investigator Saliou Diop saliou.diop@ucad.edu.sn 00221776391154 Avenue Cheikh Anta Diop BP 5002 Fann
City Postal code Country Position/Affiliation
Dakar 00221 Senegal Principal Investigator
Role Name Email Phone Street address
Principal Investigator Benjamin Koudou guibehi.koudou@csrs.ci 0022577205263 01 BP 1174
City Postal code Country Position/Affiliation
Bouake 00225 Cote Divoire Principal Investigator
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes All of the individual participant data collected during the trial, after identification will be shared. Clinical Study Report,Informed Consent Form,Statistical Analysis Plan,Study Protocol Immediately following publication Data can be reviewed by anyone who wishes to access the data at the included link
URL Results Available Results Summary Result Posting Date First Journal Publication Date
https://www.clinicaltrials.gov/ct2/show/NCT03806452?term=SIklos&draw=2&rank=1 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