SIKAMIC (SIklos on Kidney Function and AlbuMInuria Clinical Trial)

Sickle Cell Disease Clinical Trial

— SIKAMIC  

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:

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03806452
• Other study ID #: SIK-FR-17-1
• Status: Recruiting
• Phase: Phase 2
• Start date: May 28, 2019
• Est. completion date: June 2024

Study information

• Verified date: June 2023
• Source: ADDMEDICA SASA
• Contact: Laura Thomas-bourgneuf
• Phone: + 33 1 49 70 95 83
• Email: laura.thomas-bourgneuf[@]addmedica.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 96
• Est. completion date: June 2024
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 HbSß0 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

Related Conditions & MeSH terms

• Albuminuria
• Anemia, Sickle Cell
• Sickle Cell Disease

Intervention

Drug:
• Hydroxycarbamide
Hydroxycarbamide tablets of 100 and 1000 mg
• Placebo Oral Tablet
Placebo tablets of 100 and 1000 mg to mimic hydroxycarbamide tablets

Locations

Country	Name	City	State
Côte D'Ivoire	Centre Suisse de Recherches Scientifiques en Côte d'Ivoire (CSRS)	Abidjan
France	CHU d'Angers	Angers
France	Hôpital Saint-André	Bordeaux
France	CHRU Brest	Brest
France	Hôpital Louis Mourier	Colombes
France	Pablo Bartolucci	Créteil
France	Hopital Edouard Herriot	Lyon
France	Hôpital de la Timone	Marseille
France	Hôpital européen Georges-Pompidou	Paris
France	Hôpital Saint-Antoine	Paris
France	Service de biothérapie, consultation hématologie-drépanocytose hôpital Necker	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	Institut Universitaire du Cancer de Toulouse - Oncopole	Toulouse
Guadeloupe	CHU Pointe-à-Pitre/Abymes	Pointe-à-Pitre
Mali	Centre de Recherche et de Lutte contre la Drépanocytose de Bamako (CRLD)	Bamako
Martinique	CHU Martinique	Le Lamentin
Senegal	Service d'Hématologie Clinique, Centre National de Transfusion sanguine, Université Cheikh Anta Diop	Dakar

Sponsors (1)

Lead Sponsor	Collaborator
ADDMEDICA SASA

Countries where clinical trial is conducted

Côte D'Ivoire,  France,  Guadeloupe,  Mali,  Martinique,  Senegal, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients achieving at least a 30% decrease in ACR baseline value		6 months
Secondary	Absolute mean changes in eGFR value		6 months
Secondary	Absolute mean changes in ACR value		6 months
Secondary	Proportion of patients with a shift from macroalbuminuria to microalbuminuria		6 months
Secondary	Proportion of patients with a shift from microalbuminuria to normoalbuminuria		6 months
Secondary	Proportion of patients with a shift from macroalbuminuria to normoalbuminuria		6 months
Secondary	Proportion of patients with a shift from microalbuminuria to macroalbuminuria		6 months
Secondary	Evolution curve of ACR		6 months
Secondary	Evolution curve of ACR		From treatment initiation to month 12, for responder patients willing to continue the study after 6 months.
Secondary	Evolution curve of eGFR		6 months
Secondary	Evolution curve of eGFR		From treatment initiation to month 12, for responder patients willing to continue the study after 6 months.
Secondary	Identification of clinical markers associated with response to treatment.	Reported any sickle cell disease related organopathy	6 months
Secondary	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
Secondary	Incidence of treatment-emergent AEs and SAEs		Through study completion
Secondary	Absolute mean changes of systolic blood pressure		6 months and 12 months for responder patients willing to continue the study after month 6.
Secondary	Absolute mean changes of body mass index		6 months and 12 months for responder patients willing to continue the study after month 6.
Secondary	Absolute mean changes of diastolic blood pressure		6 months and 12 months for responder patients willing to continue the study after month 6.
Secondary	Absolute mean changes of heart rate measure		6 months and 12 months for responder patients willing to continue the study after month 6.
Secondary	Absolute mean changes in white blood cells count		6 months and 12 months for responder patients willing to continue the study after month 6.
Secondary	Absolute mean changes in platelets count		6 months and 12 months for responder patients willing to continue the study after month 6.
Secondary	Absolute mean changes in mean corpuscular volume		6 months and 12 months for responder patients willing to continue the study after month 6.
Secondary	Absolute mean changes in mean corpuscular haemoglobin concentration		6 months and 12 months for responder patients willing to continue the study after month 6.
Secondary	Absolute mean changes in mean corpuscular haemoglobin		6 months and 12 months for responder patients willing to continue the study after month 6.
Secondary	Absolute mean changes in hemoglobin count		6 months and 12 months for responder patients willing to continue the study after month 6.
Secondary	Absolute mean changes in foetal hemoglobin count		6 months and 12 months for responder patients willing to continue the study after month 6.
Secondary	Absolute mean changes in free hemoglobin count		6 months and 12 months for responder patients willing to continue the study after month 6.
Secondary	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.
Secondary	Absolute mean changes in endogenous erythropoietin count		6 months and 12 months for responder patients willing to continue the study after month 6.
Secondary	Absolute mean changes in ferritin count		6 months and 12 months for responder patients willing to continue the study after month 6.
Secondary	Absolute mean changes in lactate dehydrogenase		6 months and 12 months for responder patients willing to continue the study after month 6.
Secondary	Absolute mean changes in Aspartate aminotransferase		6 months and 12 months for responder patients willing to continue the study after month 6.
Secondary	Absolute mean changes in Alanine Amino Transferase		6 months and 12 months for responder patients willing to continue the study after month 6.
Secondary	Absolute mean changes in blood urea nitrogen		6 months and 12 months for responder patients willing to continue the study after month 6.
Secondary	Absolute mean changes in conjugated bilirubin		6 months and 12 months for responder patients willing to continue the study after month 6.
Secondary	Absolute mean changes in total bilirubin		6 months and 12 months for responder patients willing to continue the study after month 6.
Secondary	Absolute mean changes in reticulocytes		6 months and 12 months for responder patients willing to continue the study after month 6.
Secondary	Rate of SCD-related clinical events		6 months and 12 months for responder patients willing to continue the study after month 6.
Secondary	Biomarkers predictive of SCN (only French patients)		6 months and 12 months for responder patients willing to continue the study after month 6.