Study Evaluating Patients With Cystinuria and Efficacy and Safety Exploratory Study in the Youngest Children

May 8, 2023 updated by: Advicenne Pharma

A Multicentre, Randomized, Controlled Versus Placebo, Double-blinded, 4 Parallel Arms, Dose-ranging Main Study, to Evaluate the Efficacy, Safety and Tolerability and Acceptability of Repeated Doses of ADV7103, After 7 Days of Treatment, in Patients With Cystinuria, and an Efficacy and Safety Exploratory Study in the Youngest Children.

This is a multicenter, randomized, controlled versus placebo, double-blinded, 4 parallel arms, dose-ranging main study, to evaluate the efficacy, safety and tolerability, and acceptability of repeated doses of ADV7103, after 7 days of treatment, in patients with cystinuria, and an efficacy and safety exploratory study in the youngest children.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

The study will target enrolling at least 15 subjects in each of the following age groups: 6 months - 5 years (B13CS part only); 6-11 years; 12-17 years and adults>18. Subjects will be in the study for up to 7 weeks.

After screening and enrollment (up to 35 days), Eligible patients will be treated will alkalinizing treatment (SoC) at the well-adapted dose and regimen for 7 days. An in-patient visit is planned at the end of this period. The baseline evaluations, including urine pH and specific gravity, will be done during this inpatient visit, from Day -1 t0 to t24h. After this visit, patients are randomized in a balanced manner (1:1:1:1) to one of the 4 possible treatment arms, ADV7103 at a low dose, medium dose or high dose, or ADV7103 placebo. For patients in B13CS part, a period of titration is planned before the 7 days of treatment with ADV7103. No use of placebo in B13CS.

Controls of urine pH will be done at the patient's home with a pocket glass electrode pH-meter on fresh urines, at least twice a day: before the administration of ADV7103, in the morning at t0 and in the evening at t12h (12hrs after last ADV7103 intake and before the next dose).

Subjects will have the opportunity to subsequently enter a long-term, open-label extension.

Study Type

Interventional

Enrollment (Anticipated)

72

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Brussels, Belgium
        • Cliniques Universitaires Saint-Luc
        • Contact:
          • Vinciane De Backer
          • Phone Number: 003216342201
        • Principal Investigator:
          • Valentine Gillion
      • Leuven, Belgium
        • UZ Leuven, Gasthuisberg Hospital
        • Contact:
        • Principal Investigator:
          • Elena Levtchenko
  • France
      • Bron, France, 69500
        • Centre Hospitalier Universitaire de Lyon - Hôpital Femme Mère Enfant
        • Contact:
        • Principal Investigator:
          • Aurélie Bertholet
      • Grenoble Cedex, France, 38043
        • CHU Grenoble
        • Contact:
          • Phone Number: (33) 4 76 76 58 94
        • Principal Investigator:
          • Guylhène Bourdat-Michel
      • Lille, France, 59000
        • CHRU Lille
        • Contact:
          • Phone Number: (33) 3 20 44 50 70
        • Principal Investigator:
          • Robert Novo
      • Paris, France, 75015
        • Hopital Necker Enfants Malades
        • Contact:
        • Principal Investigator:
          • Olivia Boyer
      • Paris, France, 15013
        • CHU Pitié-Salpêtrière
        • Contact:
          • Phone Number: (33) 1 42 17 72 07
        • Principal Investigator:
          • Isabelle Tostivint
      • Paris, France, 75015
        • Hôpital Necker AP-HP
        • Contact:
        • Principal Investigator:
          • Bertrand Knebelmann
      • Paris, France, 75020
        • Hôpital Ténon - Explorations fonctionnelles Mutlidisciplinaires et INSERM UMR S 1155
        • Contact:
          • Phone Number: (33) 1 56 01 67 73
        • Principal Investigator:
          • Emmanuel Letavernier
      • Reims, France, 51100
        • CHU Reims
        • Contact:
          • Phone Number: (33) 3 26 78 76 38
        • Principal Investigator:
          • Philippe Rieu
      • Reims, France, 51092
        • Hôpital Américain CHU de Reims
        • Contact:
          • Phone Number: (33) 3 26 78 74 89
        • Principal Investigator:
          • Christine Pietrement
      • Toulouse cedex 9, France, 31059
        • CHU Purpan
        • Contact:
          • Phone Number: (33) 5 34 55 84 58
        • Principal Investigator:
          • Stéphane Decramer

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

6 months to 70 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 1. Patient who has a diagnosis of cystinuria based on medical diagnosis (at least one previous orcurrent episode of calculus of cystine, and/or one previous or current episode of cystine crystalluria) or on genetic diagnosis (only for patients enrolled in B13CS study).

    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 who, when treated with a second line therapy (chelator agent), presents a disease status enabling interruption of the chelator agent during the course of the B12CS-B13CS research.

    4. 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.

    5. For female patient of childbearing potential (defined by CTFG as fertile, following menarche until becoming post-menopausal unless permanently sterile*) a highly effective birth control method should be used until the end of study plus 36 hours after the last dose of IMP.

    6. 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.

    7. Patient or parents or legal representative(s) who has/have provided a signed written informed consent.

    8. Patient of ≤17 years of age for whom the assent has been collected or has been tried to be collected.

    9. 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:

  • 1. Patient treated with the second line therapy and who cannot stop cystine chelating agents (sulfhydryl compounds) during the B12CS-B13CS study.

    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, ciclosporine, potassium desodic salts,antibiotics.

    8. Patient who received potassium sparing diuretics 6 weeks before the inclusion in the study.

    9. Patient who presents contra indications to the administration of the study treatment such like known allergic reactions or hypersensitivity to the active pharmaceutical ingredients or other excipients of the formulations of the study treatment (such as lactose), history of difficult access to the oral administration route and/or conditions that may hamper compliance and/or absorption of the study treatment (e.g. any difficulty of swallowing, mal-absorption, delayed gastric emptying, oesophageal compression, intestinal obstruction or other chronic gastrointestinal disease).

    10. Patient who is admitted to hospital in emergency settings. 11. Patient who participated in a clinical trial within the last 3 months before enrolment.

    12. Patient who is at risk of non-compliance in the judgment of the investigator.

    13. Patient who could present any other condition, which in the opinion of the investigator, would preclude participation in the study.

    14. Patient who cannot be contacted in case of emergency. 15. Patient under any administrative or legal supervision.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: ADV7103 1.5 mEq/Kg/day
Patients receive ADV7103 twice a day.
Drug: ADV7103
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.
Active Comparator: ADV7103 3.0 mEq/Kg/day
Patients receive ADV7103 twice a day.
Drug: ADV7103
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.
Active Comparator: ADV7103 4.5 mEq/Kg/day
Patients receive ADV7103 twice a day.
Drug: ADV7103
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.
Placebo Comparator: Placebo
Patients receive placebo twice a day.
Drug: Placebo

Placebo is a combination of 2 mm green coated lactose granules and 2 mm white coated lactose granules.

Each dose of placebo contains a fixed ratio of 1/3 of green granules and 2/3 of white granules.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of urinary pH values ≥ 7.0 during 24h on Day 7 (after ADV7103 treatment period)
Time Frame: 24 hours
The primary endpoint is the comparison between the probability of having an urinary PH ≥ 7.0 based on all urinations during Day 7 in an ADV7103 dose versus the probability in the placebo group. All urinations on Day 7 with an evaluable pH measure will be included in the analysis. The study will be declared positive if the chance of having pH value ≥ 7.0 at each urination on D7 is superior with at least one ADV7103 treatment group than with placebo.
24 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Advicenne Pharma

Investigators

  • Study Chair: Luc-André Granier, Advicenne Pharma

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

March 1, 2024

Primary Completion (Anticipated)

May 1, 2025

Study Completion (Anticipated)

June 1, 2025

Study Registration Dates

First Submitted

October 23, 2019

First Submitted That Met QC Criteria

October 30, 2019

First Posted (Actual)

November 1, 2019

Study Record Updates

Last Update Posted (Actual)

May 9, 2023

Last Update Submitted That Met QC Criteria

May 8, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • B12CS-B13CS

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

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.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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