SIKAMIC (SIklos on Kidney Function and AlbuMInuria Clinical Trial)

Phase 2

Completed

• Conditions: Sickle Cell Disease
• Interventions: Drug: Hydroxycarbamide; Drug: Placebo Oral Tablet

• Registration Number: NCT03806452
• Lead Sponsor: Theravia

Brief Summary

The purpose of this phase IIb, international, multicentre, double-blind, randomised, placebo-controlled study is to determine the effect of hydroxycarbamide on albuminuria after 6 months of treatment in SCD adult patients.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-01-09
• Study First Submitted QC: 2019-01-14
• Study First Posted: 2019-01-16
• Study Start: 2019-05-28
• Primary Completion: 2024-05-30
• Study Completion: 2024-05-30
• Status Verified: 2025-04
• Results First Submitted: 2025-04-07
• Results First Submitted QC: 2025-04-28
• Last Update Submitted: 2025-04-28
• Results First Posted: 2025-05-14
• Last Update Posted: 2025-05-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 86

Inclusion Criteria

1. Signed and dated Informed Consent Form (ICF) by a legally competent patient.
2. Patients above 18 years.
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 potential 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 trial and for 3 months after hydroxycarbamide discontinuation.
6. Male patients with partners of childbearing potential agreeing to use a highly effective contraception during the trial and for 3 months after hydroxycarbamide discontinuation. Men with pregnant or lactating women should be advised to use a barrier method of contraception (condom) to prevent the foetus or breastfed infant from exposure to hydroxycarbamide.
7. Patients who are covered by insurance scheme according to local regulatory requierements.

Exclusion Criteria

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 6 months.
3. Patients who have had chronic blood transfusion or transfusion in the last 3 months.
4. Patients with a history of hypertension (systolic blood pressure ≥ 140 or diastolic blood pressure ≥ 90 mmHg) treated with antihypertensive agent belonging to pharmacological class of RAS inhibitor.
5. Patients who have symptoms suggestive of urinary tract infection or patients with gross haematuria.
6. Patients with a concomitant primary kidney disease.
7. 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, HIV infection, systemic lupus erythematosus, inflammatory arthropathies).
8. Patient with a stage 3, 4 or 5 chronic kidney disease (eGFR < 60 mL/min per 1.73 m2).
9. 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 could be expected in this population
10. Patients requiring long-term treatment with drugs potentially nephrotoxic (see non-exhaustive list).
11. Patients requiring ACE inhibitors or ARBs within the 3 months before inclusion regardless of the indication.
12. Patients requiring long-term treatment with non-steroid anti-inflammatory drugs.
13. Patients who have a treatment which can modify the kidney function (see non-exhaustive list) in the last 3 months.
14. Patients known to be infected with HIV.
15. Female patients who are pregnant or lactating.
16. Unreliable patients including non-compliant patients, patients with known alcoholism or drug abuse or with a history of a serious psychiatric disorder as well as patients unwilling to give informed consent or to abide by the requirements of the protocol.
17. Simultaneous participation in other clinical trials on an investigational medicinal product or previous participation within 30 days before inclusion.
18. Persons in detention by judicial or administrative decision.
19. Patients with chronic conditions that upon investigator judgment may lead to a limited life expectancy

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Hydroxycarbamide	Hydroxycarbamide	Hydroxycarbamide will be supplied as 100 mg or 1000 mg film-coated tablets. The posology will be based on the patient's body weight (bw). Hydroxycarbamide will be prescribed at a dose of 15 mg/kg bw/day and will be adminitered for 6 months. Hydroxycarbamide will be administered for 12 months for patients qualified as responders willing to continue to participate in the trial.
Placebo	Placebo Oral Tablet	Placebo will be supplied as 100 mg or 1000 mg film-coated tablets. The posology will be based on the patient's body weight (bw). Placebo will be prescribed at a dose of 15 mg/kg bw/day and will be adminitered for 6 months. Hydroxycarbamide will be administered for 12 months for patients qualified as responders willing to continue to participate in the trial.

Primary Outcome Measures

Name	Time	Method
Number of Patients Achieving at Least a 30% Decrease in ACR Baseline Value	6 months	The primary endpoint of this study is the proportion of patients in the hydroxycarbamide and placebo groups achieving at least a 30% decrease in ACR baseline value at 6 months after treatment initiation. Patients who do not achieve at least a 30% decrease of the ACR baseline value at month 6 will be considered non-responders.

Secondary Outcome Measures

Name	Time	Method
Absolute Mean Changes in eGFR Value	6 months
Absolute Mean Changes in ACR Value	6 months
Proportion of Patients With a Shift From Macroalbuminuria to Microalbuminuria	6 months
Proportion of Patients With a Shift From Microalbuminuria to Normoalbuminuria	6 months
Proportion of Patients With a Shift From Macroalbuminuria to Normoalbuminuria	6 months
Proportion of Patients With a Shift From Microalbuminuria to Macroalbuminuria	6 months
Absolute Mean Changes of Systolic Blood Pressure	6 months
Absolute Mean Changes of Body Weight	6 months
Absolute Mean Changes of Diastolic Blood Pressure	6 months
Absolute Mean Changes of Heart Rate Measure	6 months
Absolute Mean Changes in White Blood Cells Count	6 months
Absolute Mean Changes in Platelets Count	6 months
Absolute Mean Changes in Mean Corpuscular Volume	6 months
Absolute Mean Changes in Mean Corpuscular Haemoglobin Concentration	6 months
Absolute Mean Changes in Mean Corpuscular Haemoglobin	6 months
Absolute Mean Changes in Hemoglobin Count	6 months
Absolute Mean Changes in Foetal Hemoglobin Count	6 months
Absolute Mean Changes in Free Hemoglobin Count	6 months and 12 months for responder patients willing to continue the study after month 6.
Absolute Mean Changes in Dense Red Blood Cells Percentage	6 months and 12 months for responder patients willing to continue the study after month 6.
Absolute Mean Changes in Endogenous Erythropoietin Count	6 months
Absolute Mean Changes in Ferritin Count	6 months
Absolute Mean Changes in Lactate Dehydrogenase	6 months
Absolute Mean Changes in Aspartate Aminotransferase	6 months
Absolute Mean Changes in Alanine Amino Transferase	6 months
Absolute Mean Changes in Blood Urea Nitrogen	6 months
Absolute Mean Changes in Conjugated Bilirubin	6 months
Absolute Mean Changes in Total Bilirubin	6 months
Absolute Mean Changes in Reticulocytes	6 months

Trial Locations

Locations (21)

Centre de Recherche et de Lutte contre la Drépanocytose de Bamako (CRLD); 🇲🇱 Bamako, Mali

CHU Pointe-à-Pitre/Abymes; 🇬🇵 Pointe-à-Pitre, Guadeloupe

CHU d'Angers; 🇫🇷 Angers, France

Centre Suisse de Recherches Scientifiques en Côte d'Ivoire (CSRS); 🇨🇮 Abidjan, Côte D'Ivoire

Service d'Hématologie Clinique, Centre National de Transfusion sanguine, Université Cheikh Anta Diop; 🇸🇳 Dakar, Senegal

CHRU Brest; 🇫🇷 Brest, France

Hôpital Saint-André; 🇫🇷 Bordeaux, France

Hôpital de la Timone; 🇫🇷 Marseille, France

Hopital Edouard Herriot; 🇫🇷 Lyon, France

Pablo Bartolucci; 🇫🇷 Créteil, France

Hôpital européen Georges-Pompidou; 🇫🇷 Paris, France

Hôpital Saint-Antoine; 🇫🇷 Paris, France

CHU la Miletrie; 🇫🇷 Poitiers, France

Hôpital Robert Debré CHU Reims; 🇫🇷 Reims, France

Hopital Pontchaillou; 🇫🇷 Rennes, France

CHU Charles Nicolle; 🇫🇷 Rouen, France

Centre Hospitalier Delafontaine; 🇫🇷 Saint-Denis, France

Service de biothérapie, consultation hématologie-drépanocytose hôpital Necker; 🇫🇷 Paris, France

Hôpital Louis Mourier; 🇫🇷 Colombes, France

CHU Martinique; 🇲🇶 Le Lamentin, Martinique

Institut Universitaire du Cancer de Toulouse - Oncopole; 🇫🇷 Toulouse, France