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Study Evaluating Patients With Cystinuria

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: NCT04137978
Recruitment Status : Recruiting
First Posted : October 24, 2019
Last Update Posted : October 24, 2019
Sponsor:
Information provided by (Responsible Party):
Advicenne Pharma

Brief Summary:
This is an open label, multicentre study, evaluating the safety, tolerability, efficacy, compliance and acceptability of alkalising treatments at long-term in patients with cystinuria.

Condition or disease Intervention/treatment Phase
Cystinuria Drug: ADV7103 Drug: Standard of Care Phase 2 Phase 3

Detailed Description:

B14CS study is an extension study which follows the B12CS-B13CS study. Patients who have participated in B12CS-B13CS Study will have the possibility to switch to B14CS Study for a long-term treatment period (2 year-period).

The B14CS Study is an open-label long-term study and including 2 types of cohorts.

  • ADV7103 Cohort: Cohort of patients who will have completed either B12CS or B13CS Study. Following an optional titration period (for B12CS Study subjects), all patients will be maintained at their ADV7103 optimal dose for a 2-year-period.
  • SoC Cohort: Cohort of patients with cystinuria, matching-pair for age category to the patients of ADV7103 Cohort, will receive their own alkalinising treatment (SoC) taken at the usual dose and frequency and will follow their usual first intention treatment (hydration and diet) for a 2-year-period. This cohort is designed in order to contextualize the safety, tolerability and efficacy of the long-term ADV7103 treatment.

The B14CS Study will be composed of 3 periods (more detailed hereafter):

  • Lead-in Period: Period of 3 weeks, during which the treatment (ADV7103 or SoC) will be taken at the optimal dose as previously defined (Maintenance Phase). The Lead-in Period can include a Titration Phase, for ADV7103 B12CS Cohort only, in order to define the individual optimal dose of ADV7103 for the patients of this cohort;
  • Assessment Period: Period of 7 days to evaluate the effect of study products (ADV7103 and SoC) at the optimal dose;
  • Follow-up Period: Period of 23 months to evaluate the effects of the study products (ADV7103 and SoC) at long-term.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 97 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Open Label, Multicentre Study, Evaluating the Safety, Tolerability, Efficacy, Compliance and Acceptability of Alkalising Treatments at Long-term in Patients With Cystinuria
Actual Study Start Date : February 1, 2019
Estimated Primary Completion Date : August 2022
Estimated Study Completion Date : August 2022


Arm Intervention/treatment
Active Comparator: ADV7103

Patients receive ADV7103 twice a day at optimal dose. Each dose of ADV7103 contains a fixed ratio of 1/3 of ADV7103-CK (potassium citrate) and 2/3 of ADV7103-BK (potassium bicarbonate) based on the mass of active substances.

Other Names:

• Potassium Citrate and Potassium Bicarbonate

Drug: ADV7103
Patients receive ADV7103 twice a day at optimal dose.
Other Name: Potassium Citrate and Potassium Bicarbonate

Active Comparator: Standard of care comparator
Alkalinising treatment (SoC) taken at the usual dose and frequency
Drug: Standard of Care
Cohort of patients with cystinuria, matching-pair for age category to the patients of ADV7103 Cohort, will receive their own alkalinising treatment (SoC) taken at the usual dose and frequency and will follow their usual first intention treatment (hydration and diet) for a 2-year-period.




Primary Outcome Measures :
  1. Percentage of urinary pH values ≥ 7.0 during 24h on Day 7 (after ADV7103 treatment period) [ Time Frame: 7 Days ]
    To evaluate the safety and the tolerability of ADV7103 and standard of care (SoC) after a long-term treatment.



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Ages Eligible for Study:   6 Months to 70 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • For ADV7103 cohort:

    1. Patient who has participated to and completed the previous B12CS Study or B13CS Study.
    2. Patient for whom the safety and tolerability of ADV7103 were satisfactory during B12CS Study or B13CS Study.
    3. Female patient of childbearing potential (defined by the Clinical Trial Facilitation Group (CTFG) as woman fertile, following menarche until becoming post-menopausal unless permanently sterile*) using an acceptable effective birth control method** and having a negative pregnancy test at the inclusion, or a woman postmenopausal*** or a woman surgically sterilized*.
    4. Patient and/or parents or legal representative(s) who is(are) willing and able to participate in the study, to understand and to comply with study procedures for the entire length of the study.
    5. Patient or parents or legal representative(s) who has(have) provided a signed written informed consent.
    6. Patient of ≤17 Patient of ≤17 years of age for whom the assent has been collected or has been tried to be collected.
    7. Patient who is affiliated to a social health insurance system and/or in compliance with the recommendations of the national law in force relating to biomedical research.

For Standard of Care cohort:

  1. Patient who has a diagnosis of cystinuria based on medical diagnosis (at least one previous or current episode of calculus of cystine, and/or one previous or current episode of cystine crystalluria) or on genetic diagnosis (only for patients of Subset 4).
  2. Patient treated with an alkalising treatment at a well-adapted dose (defined as a daily dose deemed by the investigator aiming to maintain overtime urinary pH value ≥ 7.0 and/or compatible with an acceptable safety profile and/or patient's constraints or compliance).
  3. Patient male or female, including child aged between 6 months and 17 years old and adult aged ≥ 18 years old up to 70 years old.
  4. Female patient of childbearing potential (defined by the Clinical Trial Facilitation Group (CTFG) as woman fertile, following menarche until becoming post-menopausal unless permanently sterile*) using an acceptable effective birth control method** and having a negative pregnancy test at the inclusion, or a woman postmenopausal*** or a woman surgically sterilized*.
  5. Patient and/or parents or legal representative(s) who is(are) willing and able to participate in the study, to understand and to comply with study procedures for the entire length of the study.
  6. Patient or parents or legal representative(s) who has/have provided a signed written informed consent.
  7. Patient of ≤17 years of age for whom the assent has been collected or has been tried to be collected.
  8. Patient who is affiliated to a social health insurance system and/or in compliance with the recommendations of the national law in force relating to biomedical research.

Exclusion Criteria:

  • For ADV7103 cohort:

    1. Patient who has not participated to B12CS study or B13CS study
    2. Patient for whom any safety issue could contraindicate her/his participation to the extension study

For Standard of Care cohort:

  1. Patient that is receiving the second line therapy -- cystine chelating agents (sulfhydryl compounds).
  2. Patient who presents kalaemia > 5.0 mmol/L.
  3. Patient who presents a moderate or severe renal impairment (estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m2 according to Schwartz formula for the children and both MDRDs and CKD-EPI for adults).
  4. Patient who presents - barring the study disease - any previous or concurrent medical condition or any laboratory or clinical findings or any other condition that in the opinion of the investigator would be negatively affected by the study product or that would affect the study product or that precludes his participation, e.g. uncontrolled diabetes mellitus, adrenal insufficiency, cardiac impairment, repeated infections, metabolic alkalosis, chronic diarrhoea.
  5. Female patient who is pregnant or breast-feeding.
  6. Patient who cannot stop potassium sparing diuretics (e.g. antagonists of aldosterone as such spironolactone, canrenoate and eplerenone, amiloride, triamterene), angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists, tacrolimus, potassium desodic salts.
  7. Patient who received any medication that could interfere with the study treatment within 4 weeks before the inclusion in the study, including angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists, tacrolimus, potassium desodic salts, antibiotics.
  8. Patient who received potassium sparing diuretics 6 weeks before the inclusion in the study.
  9. Patient who is admitted to hospital in emergency settings.
  10. Patient who participated in a clinical trial within the last 3 months before enrolment.
  11. Patient who is at risk of non-compliance in the judgment of the investigator.
  12. Patient who could present any other condition, which in the opinion of the investigator, would preclude participation in the study.
  13. Patient who cannot be contacted in case of emergency.
  14. Patient under any administrative or legal supervision.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04137978


Locations
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Belgium
Cliniques Universitaires Saint-Luc Not yet recruiting
Brussels, Belgium
Contact: Vinciane De Backer    003216342201      
Principal Investigator: Valentine Gillion         
UZ Leuven, Gasthuisberg Hospital Not yet recruiting
Leuven, Belgium
Contact: Caroline Huget    003216342201    caroline.huget@uzleuven.be   
Principal Investigator: Elena Levtchenko         
France
CHU de Bordeaux - Hôpital Pellegrin Not yet recruiting
Bordeaux, France, 33076
Contact: Julien Dumur    (33) 5 57 82 18 53    Julien.dumur.ext@chu-bordeaux.fr   
Principal Investigator: Jérôme Harambat         
Centre Hospitalier Universitaire de Lyon Not yet recruiting
Bron, France, 69500
Contact: Ségolène Gaillard    (33) 4 27 85 77 28    segolene.gaillard@chu-lyon.fr   
Principal Investigator: Aurélie Bertholet         
CHU Grenoble Not yet recruiting
Grenoble Cedex, France, 38043
Contact    (33) 4 76 76 58 94      
Principal Investigator: Guylhène Bourdat-Michel         
CHRU Lille Not yet recruiting
Lille, France, 59000
Contact    (33) 3 20 44 50 70      
Principal Investigator: Robert Novo         
CHU Pitié-Salpétrière Not yet recruiting
Paris, France, 15013
Contact    (33) 1 42 17 72 07      
Principal Investigator: Isabelle Tostivint         
Hôpital Necker AP-HP Recruiting
Paris, France, 75015
Contact: Magatte Fall    (33) 1 44 49 45 75    magatte.fall@aphp.fr   
Principal Investigator: Bertrand Knebelmann         
Hôpital Necker Enfants Malades Not yet recruiting
Paris, France, 75015
Contact: Magatte Fall    (33) 1 44 49 45 75    magatte.fall@aphp.fr   
Principal Investigator: Olivia Boyer         
Hôpital Ténon - Explorations fonctionnelles Mutlidisciplinaires et INSERM UMR S 1155 Not yet recruiting
Paris, France, 75020
Contact    (33) 1 56 01 67 73      
Principal Investigator: Emmanuel Letavernier         
Hôpital Américain CHU de Reims Not yet recruiting
Reims, France, 51092
Contact    (33) 3 26 78 74 89      
Principal Investigator: Christine Pietrement         
CHU Reims Not yet recruiting
Reims, France, 51100
Contact    (33) 3 26 78 76 38      
Principal Investigator: Philippe Rieu         
CHU Purpan Not yet recruiting
Toulouse cedex 9, France, 31059
Contact    (33) 5 34 55 84 58      
Principal Investigator: Stéphane Decramer         
Sponsors and Collaborators
Advicenne Pharma
Investigators
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Study Director: Luc-André Granier, M.D. Advicenne Pharma

Additional Information:
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Responsible Party: Advicenne Pharma
ClinicalTrials.gov Identifier: NCT04137978    
Other Study ID Numbers: B14CS
First Posted: October 24, 2019    Key Record Dates
Last Update Posted: October 24, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Cystinuria
Renal Aminoacidurias
Renal Tubular Transport, Inborn Errors
Kidney Diseases
Urologic Diseases
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases
Potassium Citrate
Citric Acid
Anticoagulants
Calcium Chelating Agents
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action
Diuretics
Natriuretic Agents
Physiological Effects of Drugs
Expectorants
Respiratory System Agents