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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03806452
Recruitment Status : Recruiting
First Posted : January 16, 2019
Last Update Posted : January 27, 2023
Sponsor:
Information provided by (Responsible Party):
ADDMEDICA SASA

Tracking Information
First Submitted Date  ICMJE January 9, 2019
First Posted Date  ICMJE January 16, 2019
Last Update Posted Date January 27, 2023
Actual Study Start Date  ICMJE May 28, 2019
Estimated Primary Completion Date June 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 8, 2020)		 Proportion of patients achieving at least a 30% decrease in ACR baseline value [ Time Frame: 6 months ]
Original Primary Outcome Measures  ICMJE
 (submitted: January 14, 2019)		 Proportion of patients achieving at least a 30% decrease in ACR baseline value [ Time Frame: 12 months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 8, 2020)
  • Absolute mean changes in eGFR value [ Time Frame: 6 months ]
  • Absolute mean changes in ACR value [ Time Frame: 6 months ]
  • Proportion of patients with a shift from macroalbuminuria to microalbuminuria [ Time Frame: 6 months ]
  • Proportion of patients with a shift from microalbuminuria to normoalbuminuria [ Time Frame: 6 months ]
  • Proportion of patients with a shift from macroalbuminuria to normoalbuminuria [ Time Frame: 6 months ]
  • Proportion of patients with a shift from microalbuminuria to macroalbuminuria [ Time Frame: 6 months ]
  • Evolution curve of ACR [ Time Frame: 6 months ]
  • Evolution curve of ACR [ Time Frame: From treatment initiation to month 12, for responder patients willing to continue the study after 6 months. ]
  • Evolution curve of eGFR [ Time Frame: 6 months ]
  • Evolution curve of eGFR [ Time Frame: 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. [ Time Frame: 6 months ]
    Reported any sickle cell disease related organopathy
  • Identification of biological markers associated with response to treatment. [ Time Frame: 6 months ]
    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.
  • Incidence of treatment-emergent AEs and SAEs [ Time Frame: Through study completion ]
  • Absolute mean changes of systolic blood pressure [ Time Frame: 6 months and 12 months for responder patients willing to continue the study after month 6. ]
  • Absolute mean changes of body mass index [ Time Frame: 6 months and 12 months for responder patients willing to continue the study after month 6. ]
  • Absolute mean changes of diastolic blood pressure [ Time Frame: 6 months and 12 months for responder patients willing to continue the study after month 6. ]
  • Absolute mean changes of heart rate measure [ Time Frame: 6 months and 12 months for responder patients willing to continue the study after month 6. ]
  • Absolute mean changes in white blood cells count [ Time Frame: 6 months and 12 months for responder patients willing to continue the study after month 6. ]
  • Absolute mean changes in platelets count [ Time Frame: 6 months and 12 months for responder patients willing to continue the study after month 6. ]
  • Absolute mean changes in mean corpuscular volume [ Time Frame: 6 months and 12 months for responder patients willing to continue the study after month 6. ]
  • Absolute mean changes in mean corpuscular haemoglobin concentration [ Time Frame: 6 months and 12 months for responder patients willing to continue the study after month 6. ]
  • Absolute mean changes in mean corpuscular haemoglobin [ Time Frame: 6 months and 12 months for responder patients willing to continue the study after month 6. ]
  • Absolute mean changes in hemoglobin count [ Time Frame: 6 months and 12 months for responder patients willing to continue the study after month 6. ]
  • Absolute mean changes in foetal hemoglobin count [ Time Frame: 6 months and 12 months for responder patients willing to continue the study after month 6. ]
  • Absolute mean changes in free hemoglobin count [ Time Frame: 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 [ Time Frame: 6 months and 12 months for responder patients willing to continue the study after month 6. ]
  • Absolute mean changes in endogenous erythropoietin count [ Time Frame: 6 months and 12 months for responder patients willing to continue the study after month 6. ]
  • Absolute mean changes in ferritin count [ Time Frame: 6 months and 12 months for responder patients willing to continue the study after month 6. ]
  • Absolute mean changes in lactate dehydrogenase [ Time Frame: 6 months and 12 months for responder patients willing to continue the study after month 6. ]
  • Absolute mean changes in Aspartate aminotransferase [ Time Frame: 6 months and 12 months for responder patients willing to continue the study after month 6. ]
  • Absolute mean changes in Alanine Amino Transferase [ Time Frame: 6 months and 12 months for responder patients willing to continue the study after month 6. ]
  • Absolute mean changes in blood urea nitrogen [ Time Frame: 6 months and 12 months for responder patients willing to continue the study after month 6. ]
  • Absolute mean changes in conjugated bilirubin [ Time Frame: 6 months and 12 months for responder patients willing to continue the study after month 6. ]
  • Absolute mean changes in total bilirubin [ Time Frame: 6 months and 12 months for responder patients willing to continue the study after month 6. ]
  • Absolute mean changes in reticulocytes [ Time Frame: 6 months and 12 months for responder patients willing to continue the study after month 6. ]
  • Rate of SCD-related clinical events [ Time Frame: 6 months and 12 months for responder patients willing to continue the study after month 6. ]
  • Biomarkers predictive of SCN (only French patients) [ Time Frame: 6 months and 12 months for responder patients willing to continue the study after month 6. ]
Original Secondary Outcome Measures  ICMJE
 (submitted: January 14, 2019)
  • Absolute mean changes in eGFR value [ Time Frame: 6 and 12 months ]
  • Proportion of patients achieving at least a 30% decrease in ACR baseline value [ Time Frame: 6 months ]
  • Absolute mean changes in ACR value [ Time Frame: 6 and 12 months ]
  • Improvement in albuminuria stage [ Time Frame: 6 and 12 months ]
  • Progression from microalbuminuria to macroalbuminuria [ Time Frame: 6 and 12 months ]
  • Evolution curve of ACR [ Time Frame: 6 and 12 months ]
  • Evolution curve of eGFR [ Time Frame: 6 and 12 months ]
  • Identification of clinical markers associated with response to treatment. [ Time Frame: 12 months ]
    Reported any sickle cell disease related organopathy
  • Identification of biological markers associated with response to treatment. [ Time Frame: 12 months ]
    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.
  • Treatment-emergent AEs and SAEs [ Time Frame: Through study completion, an average of 1 year ]
  • Absolute mean changes of systolic blood pressure [ Time Frame: 6 and 12 months ]
  • Absolute mean changes of body mass index [ Time Frame: 6 and 12 months ]
  • Absolute mean changes of diastolic blood pressure [ Time Frame: 6 and 12 months ]
  • Absolute mean changes of heart rate measure [ Time Frame: 6 and 12 months ]
  • Absolute mean changes in white blood cells count [ Time Frame: 6 and 12 months ]
  • Absolute mean changes in platelets count [ Time Frame: 6 and 12 months ]
  • Absolute mean changes in mean corpuscular volume [ Time Frame: 6 and 12 months ]
  • Absolute mean changes in mean corpuscular haemoglobin concentration; [ Time Frame: 6 and 12 months ]
  • Absolute mean changes in mean corpuscular haemoglobin [ Time Frame: 6 and 12 months ]
  • Absolute mean changes in hemoglobin count [ Time Frame: 6 and 12 months ]
  • Absolute mean changes in foetal hemoglobin count [ Time Frame: 6 and 12 months ]
  • Absolute mean changes in free hemoglobin count [ Time Frame: 6 and 12 months ]
  • Absolute mean changes in Dense red blood cells percentage [ Time Frame: 6 and 12 months ]
  • Absolute mean changes in endogenous erythropoietin count [ Time Frame: 6 and 12 months ]
  • Absolute mean changes in ferritin count [ Time Frame: 6 and 12 months ]
  • Absolute mean changes in lactate dehydrogenase [ Time Frame: 6 and 12 months ]
  • Absolute mean changes in Aspartate aminotransferase [ Time Frame: 6 and 12 months ]
  • Absolute mean changes in Alanine Amino Transférase [ Time Frame: 6 and 12 months ]
  • Absolute mean changes in blood urea nitrogen [ Time Frame: 6 and 12 months ]
  • Absolute mean changes in conjugated bilirubin [ Time Frame: 6 and 12 months ]
  • Absolute mean changes in total bilirubin [ Time Frame: 6 and 12 months ]
  • Absolute mean changes in reticulocytes [ Time Frame: 6 and 12 months ]
  • Rate of SCD-related clinical events [ Time Frame: 6 and 12 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE SIKAMIC (SIklos on Kidney Function and AlbuMInuria Clinical Trial)
Official Title  ICMJE 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:
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Sickle Cell Disease
Intervention  ICMJE
  • Drug: Hydroxycarbamide
    Hydroxycarbamide tablets of 100 and 1000 mg
    Other Name: Siklos
  • Drug: Placebo Oral Tablet
    Placebo tablets of 100 and 1000 mg to mimic hydroxycarbamide tablets
Study Arms  ICMJE
  • 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.

    Intervention: Drug: Hydroxycarbamide
  • 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.

    Intervention: Drug: Placebo Oral Tablet
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 26, 2023)		 96
Original Estimated Enrollment  ICMJE
 (submitted: January 14, 2019)		 120
Estimated Study Completion Date  ICMJE June 2024
Estimated Primary Completion Date June 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Laura Thomas-bourgneuf + 33 1 49 70 95 83 laura.thomas-bourgneuf@addmedica.com
Listed Location Countries  ICMJE Côte D'Ivoire,   France,   Guadeloupe,   Mali,   Martinique,   Senegal
Removed Location Countries French Guiana
 
Administrative Information
NCT Number  ICMJE NCT03806452
Other Study ID Numbers  ICMJE SIK-FR-17-1
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party ADDMEDICA SASA
Original Responsible Party Same as current
Current Study Sponsor  ICMJE ADDMEDICA SASA
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Pablo Bartolucci, Pr Henri Mondor University Hospital
Study Chair: Vincent Audard, Pr Henri Mondor University Hospital
PRS Account ADDMEDICA SASA
Verification Date March 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP