SIKAMIC (SIklos on Kidney Function and AlbuMInuria Clinical Trial) (SIKAMIC)

Multicentre Randomized Double-blind Placebo-controlled Study to Evaluate the Effect on Albuminuria of 6 Months Treatment With Hydroxycarbamide (Siklos®) or a Placebo in Adults With Sickle Cell Disease:

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.

Study Overview

• Status: Recruiting
• Conditions: Sickle Cell Disease
• Intervention / Treatment: Drug: Hydroxycarbamide; Drug: Placebo Oral Tablet

• Study Type: Interventional
• Enrollment (Estimated): 96
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Laura Thomas-bourgneuf; Phone Number: + 33 1 49 70 95 83; Email: laura.thomas-bourgneuf@addmedica.com

Study Locations

• Côte D'Ivoire
  • Abidjan, Côte D'Ivoire
    • Not yet recruiting
    • Centre Suisse de Recherches Scientifiques en Côte d'Ivoire (CSRS)
    • Contact: Aurelien Yapi, Dr
    • Principal Investigator: Aurélien Yapi, Dr
• France
  • Angers, France
    • Active, not recruiting
    • CHU d'Angers
  • Bordeaux, France
    • Active, not recruiting
    • Hopital Saint-Andre
  • Brest, France
    • Active, not recruiting
    • CHRU Brest
  • Colombes, France
    • Active, not recruiting
    • Hopital Louis Mourier
  • Créteil, France, 94017
    • Recruiting
    • Pablo Bartolucci
    • Contact: Pablo Bartolucci, Pr; Email: pablo.bartolucci@aphp.fr
    • Principal Investigator: Pablo Bartolucci, Pr
  • Lyon, France
    • Recruiting
    • Hopital Edouard Herriot
    • Contact: Giovanna Cannas; Email: giovanna.cannas@chu-lyon.fr
    • Principal Investigator: Giovanna Cannas
  • Marseille, France
    • Recruiting
    • Hôpital De La Timone
    • Contact: Estelle Jean; Email: Estelle.JEAN@ap-hm.fr
    • Principal Investigator: Estelle Jean
    • Principal Investigator: Emmanuelle Bernit
  • Paris, France
    • Recruiting
    • Hopital Europeen Georges-Pompidou
    • Contact: Jean-Benoît Arlet, Pr; Email: jean-benoit.arlet@aphp.fr
    • Principal Investigator: Jean-Benoît Arlet, Pr
  • Paris, France
    • Active, not recruiting
    • Hôpital Saint-Antoine
  • Paris, France
    • Active, not recruiting
    • Service de biothérapie, consultation hématologie-drépanocytose hôpital Necker
  • Poitiers, France
    • Recruiting
    • CHU La Miletrie
    • Contact: Justine Gellen-Dautremer; Email: justine.gellen-dautremer@chu-poitiers.fr
    • Principal Investigator: Justine Gellen-Dautremer
  • Reims, France
    • Active, not recruiting
    • Hopital Robert Debre Chu Reims
  • Rennes, France
    • Recruiting
    • Hopital Pontchaillou
    • Contact: Stanislas Nimubona; Email: stanislas.nimubona@chu-rennes.fr
    • Principal Investigator: Stanislas Nimubona
  • Rouen, France
    • Active, not recruiting
    • CHU Charles Nicolle
  • Saint-Denis, France
    • Active, not recruiting
    • Centre Hospitalier Delafontaine
  • Toulouse, France
    • Active, not recruiting
    • Institut Universitaire du Cancer de Toulouse - Oncopole
• Guadeloupe
  • Pointe-à-Pitre, Guadeloupe
    • Recruiting
    • CHU Pointe-à-Pitre/Abymes
    • Contact: Maryse Etienne-Julan; Email: maryse.etienne-julan@chu-guadeloupe.fr
    • Principal Investigator: Maryse Etienne-Julan
• Mali
  • Bamako, Mali
    • Recruiting
    • Centre de Recherche et de Lutte contre la Drépanocytose de Bamako (CRLD)
    • Contact: Aldiouma Guindo, Pr; Email: aldguindo@icermali.org
    • Principal Investigator: Aldiouma Guindo, Pr
• Martinique
  • Le Lamentin, Martinique
    • Recruiting
    • CHU Martinique
    • Contact: Gylna Loko; Email: gylna.loko@chu-martinique.fr
    • Principal Investigator: Gylna Loko
• Senegal
  • Dakar, Senegal
    • Recruiting
    • Service d'Hématologie Clinique, Centre National de Transfusion sanguine, Université Cheikh Anta Diop
    • Contact: Saliou Diop, Pr; Email: saliou.diop@ucad.edu.sn
    • Principal Investigator: Saliou Diop, Pr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Hydroxycarbamide; Hydroxycarbamide tablets of 100 and 1000 mg; Other Names: Siklos
Placebo Comparator: Placebo; 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.	Drug: Placebo Oral Tablet; Placebo tablets of 100 and 1000 mg to mimic hydroxycarbamide tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of patients achieving at least a 30% decrease in ACR baseline value	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Evolution curve of ACR		6 months
Evolution curve of ACR		From treatment initiation to month 12, for responder patients willing to continue the study after 6 months.
Evolution curve of eGFR		6 months
Evolution curve of eGFR		From treatment initiation to month 12, for responder patients willing to continue the study after 6 months.
Identification of clinical markers associated with response to treatment.	Reported any sickle cell disease related organopathy	6 months
Identification of biological markers associated with response to treatment.	Haematology: Red blood cell count and Mean Corpuscular Volume, Dense Red Blood Cells, reticulocytes, Hemoglobin, free Hemoglobin and Fetal hemoglobin, Mean Corpuscular Hemoglobin and Mean Corpuscular Hemoglobin Concentration, hematocrit, White Blood Cell counts, neutrophils, lymphocytes, monocytes, eosinophils, basophils and platelet counts, endogenous EPO and ferritin concentrations. Blood biochemistry : Renal function: blood Creatinine. Haemolysis biochemical markers: Lactate Deshydrogenase, aspartate aminotransferase, ALT, BUN, conjugated and total bilirubin.	6 months
Incidence of treatment-emergent AEs and SAEs		Through study completion
Absolute mean changes of systolic blood pressure		6 months and 12 months for responder patients willing to continue the study after month 6.
Absolute mean changes of body mass index		6 months and 12 months for responder patients willing to continue the study after month 6.
Absolute mean changes of diastolic blood pressure		6 months and 12 months for responder patients willing to continue the study after month 6.
Absolute mean changes of heart rate measure		6 months and 12 months for responder patients willing to continue the study after month 6.
Absolute mean changes in white blood cells count		6 months and 12 months for responder patients willing to continue the study after month 6.
Absolute mean changes in platelets count		6 months and 12 months for responder patients willing to continue the study after month 6.
Absolute mean changes in mean corpuscular volume		6 months and 12 months for responder patients willing to continue the study after month 6.
Absolute mean changes in mean corpuscular haemoglobin concentration		6 months and 12 months for responder patients willing to continue the study after month 6.
Absolute mean changes in mean corpuscular haemoglobin		6 months and 12 months for responder patients willing to continue the study after month 6.
Absolute mean changes in hemoglobin count		6 months and 12 months for responder patients willing to continue the study after month 6.
Absolute mean changes in foetal hemoglobin count		6 months and 12 months for responder patients willing to continue the study after month 6.
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 and 12 months for responder patients willing to continue the study after month 6.
Absolute mean changes in ferritin count		6 months and 12 months for responder patients willing to continue the study after month 6.
Absolute mean changes in lactate dehydrogenase		6 months and 12 months for responder patients willing to continue the study after month 6.
Absolute mean changes in Aspartate aminotransferase		6 months and 12 months for responder patients willing to continue the study after month 6.
Absolute mean changes in Alanine Amino Transferase		6 months and 12 months for responder patients willing to continue the study after month 6.
Absolute mean changes in blood urea nitrogen		6 months and 12 months for responder patients willing to continue the study after month 6.
Absolute mean changes in conjugated bilirubin		6 months and 12 months for responder patients willing to continue the study after month 6.
Absolute mean changes in total bilirubin		6 months and 12 months for responder patients willing to continue the study after month 6.
Absolute mean changes in reticulocytes		6 months and 12 months for responder patients willing to continue the study after month 6.
Rate of SCD-related clinical events		6 months and 12 months for responder patients willing to continue the study after month 6.
Biomarkers predictive of SCN (only French patients)		6 months and 12 months for responder patients willing to continue the study after month 6.

Collaborators and Investigators

• Sponsor: ADDMEDICA SASA
• Investigators: Principal Investigator: Pablo Bartolucci, Pr, Henri Mondor University Hospital; Study Chair: Vincent Audard, Pr, Henri Mondor University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 28, 2019
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): June 1, 2024

Study Registration Dates

• First Submitted: January 9, 2019
• First Submitted That Met QC Criteria: January 14, 2019
• First Posted (Actual): January 16, 2019

Study Record Updates

• Last Update Posted (Actual): June 15, 2023
• Last Update Submitted That Met QC Criteria: June 14, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: albuminuria; hydroxycarbamide
• Additional Relevant MeSH Terms: Urologic Diseases; Urological Manifestations; Hematologic Diseases; Genetic Diseases, Inborn; Urination Disorders; Anemia; Proteinuria; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Albuminuria; Anemia, Sickle Cell; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Antisickling Agents; Hydroxyurea
• Other Study ID Numbers: SIK-FR-17-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No