Clinical trial NCT03806452: SIKAMIC (SIklos on Kidney Function and AlbuMInuria Clinical Trial)
Official title: 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:
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Sickle Cell Disease
Keywords: albuminuria
hydroxycarbamide
Lead sponsor: Theravia
Sponsor class: INDUSTRY
First posted: 2019-01-16
Enrollment: 86
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of Patients Achieving at Least a 30% Decrease in ACR Baseline Value
timeFrame: 6 months
Secondary outcomes:
measure: Absolute Mean Changes in eGFR Value
timeFrame: 6 months
measure: Absolute Mean Changes in ACR Value
timeFrame: 6 months
measure: Proportion of Patients With a Shift From Macroalbuminuria to Microalbuminuria
timeFrame: 6 months
measure: Proportion of Patients With a Shift From Microalbuminuria to Normoalbuminuria
timeFrame: 6 months
measure: Proportion of Patients With a Shift From Macroalbuminuria to Normoalbuminuria
timeFrame: 6 months
measure: Proportion of Patients With a Shift From Microalbuminuria to Macroalbuminuria
timeFrame: 6 months
measure: Absolute Mean Changes of Systolic Blood Pressure
timeFrame: 6 months
measure: Absolute Mean Changes of Body Weight
timeFrame: 6 months
measure: Absolute Mean Changes of Diastolic Blood Pressure
timeFrame: 6 months
measure: Absolute Mean Changes of Heart Rate Measure
timeFrame: 6 months
measure: Absolute Mean Changes in White Blood Cells Count
timeFrame: 6 months
measure: Absolute Mean Changes in Platelets Count
timeFrame: 6 months
measure: Absolute Mean Changes in Mean Corpuscular Volume
timeFrame: 6 months
measure: Absolute Mean Changes in Mean Corpuscular Haemoglobin Concentration
timeFrame: 6 months
measure: Absolute Mean Changes in Mean Corpuscular Haemoglobin
timeFrame: 6 months
measure: Absolute Mean Changes in Hemoglobin Count
timeFrame: 6 months
measure: Absolute Mean Changes in Foetal Hemoglobin Count
timeFrame: 6 months
measure: Absolute Mean Changes in Free Hemoglobin Count
timeFrame: 6 months and 12 months for responder patients willing to continue the study after month 6.
measure: Absolute Mean Changes in Dense Red Blood Cells Percentage
timeFrame: 6 months and 12 months for responder patients willing to continue the study after month 6.
measure: Absolute Mean Changes in Endogenous Erythropoietin Count
timeFrame: 6 months
measure: Absolute Mean Changes in Ferritin Count
timeFrame: 6 months
measure: Absolute Mean Changes in Lactate Dehydrogenase
timeFrame: 6 months
measure: Absolute Mean Changes in Aspartate Aminotransferase
timeFrame: 6 months
measure: Absolute Mean Changes in Alanine Amino Transferase
timeFrame: 6 months
measure: Absolute Mean Changes in Blood Urea Nitrogen
timeFrame: 6 months
measure: Absolute Mean Changes in Conjugated Bilirubin
timeFrame: 6 months
measure: Absolute Mean Changes in Total Bilirubin
timeFrame: 6 months
measure: Absolute Mean Changes in Reticulocytes
timeFrame: 6 months
Other outcomes:
Locations:
city: Abidjan
country: Côte D'Ivoire
facility: Centre Suisse de Recherches Scientifiques en Côte d'Ivoire (CSRS)
city: Angers
country: France
facility: CHU d'Angers
city: Bordeaux
country: France
facility: Hôpital Saint-André
city: Brest
country: France
facility: CHRU Brest
city: Colombes
country: France
facility: Hôpital Louis Mourier
city: Créteil
country: France
facility: Pablo Bartolucci
city: Lyon
country: France
facility: Hopital Edouard Herriot
city: Marseille
country: France
facility: Hôpital de la Timone
city: Paris
country: France
facility: Hôpital européen Georges-Pompidou
city: Paris
country: France
facility: Hôpital Saint-Antoine
city: Paris
country: France
facility: Service de biothérapie, consultation hématologie-drépanocytose hôpital Necker
city: Poitiers
country: France
facility: CHU la Miletrie
city: Reims
country: France
facility: Hôpital Robert Debré CHU Reims
city: Rennes
country: France
facility: Hopital Pontchaillou
city: Rouen
country: France
facility: CHU Charles Nicolle
city: Saint-Denis
country: France
facility: Centre Hospitalier Delafontaine
city: Toulouse
country: France
facility: Institut Universitaire du Cancer de Toulouse - Oncopole
city: Pointe-à-Pitre
country: Guadeloupe
facility: CHU Pointe-à-Pitre/Abymes
city: Bamako
country: Mali
facility: Centre de Recherche et de Lutte contre la Drépanocytose de Bamako (CRLD)
city: Le Lamentin
country: Martinique
facility: CHU Martinique
city: Dakar
country: Senegal
facility: Service d'Hématologie Clinique, Centre National de Transfusion sanguine, Université Cheikh Anta Diop
Study officials:
affiliation: Henri Mondor University Hospital
name: Pablo Bartolucci, Pr
role: PRINCIPAL_INVESTIGATOR
affiliation: Henri Mondor University Hospital
name: Vincent Audard, Pr
role: STUDY_CHAIR
References: