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CompletedNCT03806452SIKAMICUpdated May 14, 2025Results posted

SIKAMIC (SIklos on Kidney Function and AlbuMInuria Clinical Trial)

A Phase 2 interventional study of Hydroxycarbamide and Placebo Oral Tablet in Sickle Cell Disease, sponsored by Theravia. Completed at 21 sites in 6 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-05-14.

Sponsored by Theravia · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
86
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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.

02

Conditions studied

  • Sickle Cell Disease

Keywords

  • albuminuria
  • hydroxycarbamide
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Care provider, Investigator)
Enrollment
86 participants (actual)

Study arms

  • 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

  • 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

Interventions

  • DrugHydroxycarbamide

    Hydroxycarbamide tablets of 100 and 1000 mg

    Also known as: Siklos

  • DrugPlacebo Oral Tablet

    Placebo tablets of 100 and 1000 mg to mimic hydroxycarbamide tablets

05

What researchers measure

Primary outcomes

  1. Number of Patients Achieving at Least a 30% Decrease in ACR Baseline Value

    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.

    Time frame: 6 months

Secondary outcomes

  1. Absolute Mean Changes in eGFR Value

    Time frame: 6 months

  2. Absolute Mean Changes in ACR Value

    Time frame: 6 months

  3. Proportion of Patients With a Shift From Macroalbuminuria to Microalbuminuria

    Time frame: 6 months

  4. Proportion of Patients With a Shift From Microalbuminuria to Normoalbuminuria

    Time frame: 6 months

  5. Proportion of Patients With a Shift From Macroalbuminuria to Normoalbuminuria

    Time frame: 6 months

  6. Proportion of Patients With a Shift From Microalbuminuria to Macroalbuminuria

    Time frame: 6 months

  7. Absolute Mean Changes of Systolic Blood Pressure

    Time frame: 6 months

  8. Absolute Mean Changes of Body Weight

    Time frame: 6 months

  9. Absolute Mean Changes of Diastolic Blood Pressure

    Time frame: 6 months

  10. Absolute Mean Changes of Heart Rate Measure

    Time frame: 6 months

  11. Absolute Mean Changes in White Blood Cells Count

    Time frame: 6 months

  12. Absolute Mean Changes in Platelets Count

    Time frame: 6 months

  13. Absolute Mean Changes in Mean Corpuscular Volume

    Time frame: 6 months

  14. Absolute Mean Changes in Mean Corpuscular Haemoglobin Concentration

    Time frame: 6 months

  15. Absolute Mean Changes in Mean Corpuscular Haemoglobin

    Time frame: 6 months

  16. Absolute Mean Changes in Hemoglobin Count

    Time frame: 6 months

  17. Absolute Mean Changes in Foetal Hemoglobin Count

    Time frame: 6 months

  18. 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.

  19. 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.

  20. Absolute Mean Changes in Endogenous Erythropoietin Count

    Time frame: 6 months

  21. Absolute Mean Changes in Ferritin Count

    Time frame: 6 months

  22. Absolute Mean Changes in Lactate Dehydrogenase

    Time frame: 6 months

  23. Absolute Mean Changes in Aspartate Aminotransferase

    Time frame: 6 months

  24. Absolute Mean Changes in Alanine Amino Transferase

    Time frame: 6 months

  25. Absolute Mean Changes in Blood Urea Nitrogen

    Time frame: 6 months

  26. Absolute Mean Changes in Conjugated Bilirubin

    Time frame: 6 months

  27. Absolute Mean Changes in Total Bilirubin

    Time frame: 6 months

  28. Absolute Mean Changes in Reticulocytes

    Time frame: 6 months

06

Results

Posted May 14, 2025

Participant flow

From 28 May 2019 to 30 May 2024, 86 patients were included in the study in the mITT population and analysed in France and Africa (Mali, Ivory Coast and Senegal).

Initial Treatment Period
Participant flow — Initial Treatment Period
MilestoneHydroxycarbamidePlacebo
Started4640
Completed4438
Not completed22
Responders Extended Treatment Period
Participant flow — Responders Extended Treatment Period
MilestoneHydroxycarbamidePlacebo
Started1815
Completed159
Not completed36

Outcome measures

PrimaryNumber of Patients Achieving at Least a 30% Decrease in ACR Baseline Value

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.

Time frame:
6 months
Reported as:
Count of participants · Participants
Number of Patients Achieving at Least a 30% Decrease in ACR Baseline Value
ParticipantsHydroxycarbamidePlacebo
Number of Patients Achieving at Least a 30% Decrease in ACR Baseline Value1815
SecondaryAbsolute Mean Changes in eGFR Value
Time frame:
6 months
Reported as:
Mean · ml/min/1.73m2
Absolute Mean Changes in eGFR Value
ml/min/1.73m2HydroxycarbamidePlacebo
Absolute Mean Changes in eGFR Value3.2 ± 18.5-1.0 ± 13.8
SecondaryAbsolute Mean Changes in ACR Value
Time frame:
6 months
Reported as:
Mean · mg/mmol
Absolute Mean Changes in ACR Value
mg/mmolHydroxycarbamidePlacebo
Absolute Mean Changes in ACR Value3.5 ± 19.71.0 ± 13.1
SecondaryProportion of Patients With a Shift From Macroalbuminuria to Microalbuminuria
Time frame:
6 months
Reported as:
Count of participants · Participants
Proportion of Patients With a Shift From Macroalbuminuria to Microalbuminuria
ParticipantsHydroxycarbamidePlacebo
Proportion of Patients With a Shift From Macroalbuminuria to Microalbuminuria12
SecondaryProportion of Patients With a Shift From Microalbuminuria to Normoalbuminuria
Time frame:
6 months
Reported as:
Count of participants · Participants
Proportion of Patients With a Shift From Microalbuminuria to Normoalbuminuria
ParticipantsHydroxycarbamidePlacebo
Proportion of Patients With a Shift From Microalbuminuria to Normoalbuminuria107
SecondaryProportion of Patients With a Shift From Macroalbuminuria to Normoalbuminuria
Time frame:
6 months
Reported as:
Count of participants · Participants
Proportion of Patients With a Shift From Macroalbuminuria to Normoalbuminuria
ParticipantsHydroxycarbamidePlacebo
Proportion of Patients With a Shift From Macroalbuminuria to Normoalbuminuria10
SecondaryProportion of Patients With a Shift From Microalbuminuria to Macroalbuminuria
Time frame:
6 months
Reported as:
Count of participants · Participants
Proportion of Patients With a Shift From Microalbuminuria to Macroalbuminuria
ParticipantsHydroxycarbamidePlacebo
Proportion of Patients With a Shift From Microalbuminuria to Macroalbuminuria33
SecondaryAbsolute Mean Changes of Systolic Blood Pressure
Time frame:
6 months
Reported as:
Mean · mmHg
Absolute Mean Changes of Systolic Blood Pressure
mmHgHydroxycarbamidePlacebo
Absolute Mean Changes of Systolic Blood Pressure2.8 ± 10.72.2 ± 13.1
SecondaryAbsolute Mean Changes of Body Weight
Time frame:
6 months
Reported as:
Mean · kg
Absolute Mean Changes of Body Weight
kgHydroxycarbamidePlacebo
Absolute Mean Changes of Body Weight2.2 ± 3.0-0.3 ± 2.1
SecondaryAbsolute Mean Changes of Diastolic Blood Pressure
Time frame:
6 months
Reported as:
Mean · mmHg
Absolute Mean Changes of Diastolic Blood Pressure
mmHgHydroxycarbamidePlacebo
Absolute Mean Changes of Diastolic Blood Pressure2.5 ± 13.3-1.0 ± 12.9
SecondaryAbsolute Mean Changes of Heart Rate Measure
Time frame:
6 months
Reported as:
Mean · beats/minute
Absolute Mean Changes of Heart Rate Measure
beats/minuteHydroxycarbamidePlacebo
Absolute Mean Changes of Heart Rate Measure-2.1 ± 11.32.4 ± 12.5
SecondaryAbsolute Mean Changes in White Blood Cells Count
Time frame:
6 months
Reported as:
Mean · cells/mm3
Absolute Mean Changes in White Blood Cells Count
cells/mm3HydroxycarbamidePlacebo
Absolute Mean Changes in White Blood Cells Count-3659.6 ± 3524.4-228.4 ± 2982.1
SecondaryAbsolute Mean Changes in Platelets Count
Time frame:
6 months
Reported as:
Mean · 10^9 platelets per liter
Absolute Mean Changes in Platelets Count
10^9 platelets per literHydroxycarbamidePlacebo
Absolute Mean Changes in Platelets Count-49.3 ± 150.9-16.0 ± 83.5
SecondaryAbsolute Mean Changes in Mean Corpuscular Volume
Time frame:
6 months
Reported as:
Mean · fL
Absolute Mean Changes in Mean Corpuscular Volume
fLHydroxycarbamidePlacebo
Absolute Mean Changes in Mean Corpuscular Volume15.1 ± 10.8-0.3 ± 3.4
SecondaryAbsolute Mean Changes in Mean Corpuscular Haemoglobin Concentration
Time frame:
6 months
Reported as:
Mean · g/L
Absolute Mean Changes in Mean Corpuscular Haemoglobin Concentration
g/LHydroxycarbamidePlacebo
Absolute Mean Changes in Mean Corpuscular Haemoglobin Concentration1.7 ± 15.8-4.8 ± 16.4
SecondaryAbsolute Mean Changes in Mean Corpuscular Haemoglobin
Time frame:
6 months
Reported as:
Mean · pg
Absolute Mean Changes in Mean Corpuscular Haemoglobin
pgHydroxycarbamidePlacebo
Absolute Mean Changes in Mean Corpuscular Haemoglobin5.5 ± 4.0-0.8 ± 1.6
SecondaryAbsolute Mean Changes in Hemoglobin Count
Time frame:
6 months
Reported as:
Mean · g/L
Absolute Mean Changes in Hemoglobin Count
g/LHydroxycarbamidePlacebo
Absolute Mean Changes in Hemoglobin Count12 ± 11.3-2.2 ± 6.1
SecondaryAbsolute Mean Changes in Foetal Hemoglobin Count
Time frame:
6 months
Reported as:
Mean · percentage of hemoglobin
Absolute Mean Changes in Foetal Hemoglobin Count
percentage of hemoglobinHydroxycarbamidePlacebo
Absolute Mean Changes in Foetal Hemoglobin Count8.5 ± 8.80.3 ± 1.9
SecondaryAbsolute Mean Changes in Free Hemoglobin Count
Time frame:
6 months and 12 months for responder patients willing to continue the study after month 6.

Results for this outcome have not been posted.

SecondaryAbsolute 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.

Results for this outcome have not been posted.

SecondaryAbsolute Mean Changes in Endogenous Erythropoietin Count
Time frame:
6 months
Reported as:
Mean · U/L
Absolute Mean Changes in Endogenous Erythropoietin Count
U/LHydroxycarbamidePlacebo
Absolute Mean Changes in Endogenous Erythropoietin Count-8.2 ± 22.117.4 ± 37.1
SecondaryAbsolute Mean Changes in Ferritin Count
Time frame:
6 months
Reported as:
Mean · µg/L
Absolute Mean Changes in Ferritin Count
µg/LHydroxycarbamidePlacebo
Absolute Mean Changes in Ferritin Count28.1 ± 664.2-8.0 ± 404.3
SecondaryAbsolute Mean Changes in Lactate Dehydrogenase
Time frame:
6 months
Reported as:
Mean · U/L
Absolute Mean Changes in Lactate Dehydrogenase
U/LHydroxycarbamidePlacebo
Absolute Mean Changes in Lactate Dehydrogenase-170.5 ± 349.4-1.8 ± 220.9
SecondaryAbsolute Mean Changes in Aspartate Aminotransferase
Time frame:
6 months
Reported as:
Mean · U/L
Absolute Mean Changes in Aspartate Aminotransferase
U/LHydroxycarbamidePlacebo
Absolute Mean Changes in Aspartate Aminotransferase-8.7 ± 19.2-1.0 ± 10.9
SecondaryAbsolute Mean Changes in Alanine Amino Transferase
Time frame:
6 months
Reported as:
Mean · U/L
Absolute Mean Changes in Alanine Amino Transferase
U/LHydroxycarbamidePlacebo
Absolute Mean Changes in Alanine Amino Transferase-1.7 ± 51.2-0.2 ± 13.7
SecondaryAbsolute Mean Changes in Blood Urea Nitrogen
Time frame:
6 months
Reported as:
Mean · mmol/L
Absolute Mean Changes in Blood Urea Nitrogen
mmol/LHydroxycarbamidePlacebo
Absolute Mean Changes in Blood Urea Nitrogen-0.5 ± 6.40.5 ± 2.6
SecondaryAbsolute Mean Changes in Conjugated Bilirubin
Time frame:
6 months
Reported as:
Mean · µmol/L
Absolute Mean Changes in Conjugated Bilirubin
µmol/LHydroxycarbamidePlacebo
Absolute Mean Changes in Conjugated Bilirubin-0.7 ± 33.8-1.9 ± 9.8
SecondaryAbsolute Mean Changes in Total Bilirubin
Time frame:
6 months
Reported as:
Mean · µmol/L
Absolute Mean Changes in Total Bilirubin
µmol/LHydroxycarbamidePlacebo
Absolute Mean Changes in Total Bilirubin-8.9 ± 106.54.7 ± 30.1
SecondaryAbsolute Mean Changes in Reticulocytes
Time frame:
6 months
Reported as:
Mean · cells/mm3
Absolute Mean Changes in Reticulocytes
cells/mm3HydroxycarbamidePlacebo
Absolute Mean Changes in Reticulocytes-116082.5 ± 168548.6-35336.1 ± 108156.3

Adverse events

Collected over 6 months. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Hydroxycarbamide0/46 (0%)5/46 (10.9%)30/46 (65.2%)
Placebo2/40 (5%)7/40 (17.5%)29/40 (72.5%)
Most frequent serious events
Showing 10 of 13
Most frequent serious events
EventHydroxycarbamidePlacebo
SICKLE CELL ANAEMIA WITH CRISISBlood and lymphatic system disorders2/462/40
ACUTE CHEST SYNDROMERespiratory, thoracic and mediastinal disorders0/462/40
ANAEMIABlood and lymphatic system disorders0/461/40
DYSPNOEARespiratory, thoracic and mediastinal disorders0/461/40
INFLUENZAInfections and infestations0/461/40
PNEUMONIAInfections and infestations0/461/40
HEPATOBILIARY PROCEDURAL COMPLICATIONInjury, poisoning and procedural complications0/461/40
BONE INFARCTIONMusculoskeletal and connective tissue disorders0/461/40
CHOLECYSTITISHepatobiliary disorders1/460/40
CHOLELITHIASISHepatobiliary disorders1/460/40
Most frequent other events
Showing 10 of 13
Most frequent other events
EventHydroxycarbamidePlacebo
SICKLE CELL ANAEMIA WITH CRISISBlood and lymphatic system disorders3/467/40
HEADACHENervous system disorders8/465/40
ARTHRALGIAMusculoskeletal and connective tissue disorders5/466/40
ASTHENIAGeneral disorders2/465/40
VERTIGOEar and labyrinth disorders3/465/40
CHEST PAINGeneral disorders1/464/40
PYREXIAGeneral disorders4/461/40
ABDOMINAL PAIN UPPERGastrointestinal disorders4/463/40
BACK PAINMusculoskeletal and connective tissue disorders3/463/40
FATIGUEGeneral disorders1/463/40

Baseline characteristics

Age, Continuous
Age, Continuous(years)HydroxycarbamidePlaceboTotal
Mean30.3 ± 10.030.0 ± 8.730.2 ± 9.3
Sex: Female, Male
Sex: Female, Male(Participants)HydroxycarbamidePlaceboTotal
Female322759
Male141327
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)HydroxycarbamidePlaceboTotal
Continent of origin — Africa - America454085
Continent of origin — Other101
Region of Enrollment
Region of Enrollment(participants)HydroxycarbamidePlaceboTotal
Senegal171229
Mali12820
Guadeloupe011
Côte D'Ivoire549
Martinique101
France111526
SCD genotype
SCD genotype(Participants)HydroxycarbamidePlaceboTotal
HbSS433780
HbSbeta0336
07

Study locations

21 sites
  • Centre Suisse de Recherches Scientifiques en Côte d'Ivoire (CSRS)
    Abidjan, Côte D'Ivoire
  • CHU d'Angers
    Angers, France
  • Hôpital Saint-André
    Bordeaux, France
  • CHRU Brest
    Brest, France
  • Hôpital Louis Mourier
    Colombes, France
  • Pablo Bartolucci
    Créteil, 94017, 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, France
  • CHU Pointe-à-Pitre/Abymes
    Pointe-à-Pitre, Guadeloupe
  • Centre de Recherche et de Lutte contre la Drépanocytose de Bamako (CRLD)
    Bamako, Mali
  • CHU Martinique
    Le Lamentin, Martinique
  • Service d'Hématologie Clinique, Centre National de Transfusion sanguine, Université Cheikh Anta Diop
    Dakar, Senegal
08

References and documents

Study documents

  • Protocol and statistical analysis plan · Dec 22, 2022

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

09

Registry details

Key details

Study ID
NCT03806452
Lead sponsor
Theravia
Responsible party
Sponsor
First posted
Jan 16, 2019
Start date
May 28, 2019
Primary completion
May 30, 2024
Completion
May 30, 2024
Results posted
May 14, 2025
Last update
May 14, 2025

Study contacts

Pablo Bartolucci, Pr
principal investigator · Henri Mondor University Hospital
Vincent Audard, Pr
study chair · Henri Mondor University Hospital

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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