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

NCT04147871 | Withdrawn Phase 2

• 1 other identifier: B12CS-B13CS
• Study Type: interventional
• Target: N/A
• Locations: 2 countries
• Sites: 12

Brief Summary

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.

Conditions

Cystinuria

Outcome Measures

Primary Outcomes (1)

• Percentage of urinary pH values ≥ 7.0 during 24h on Day 7 (after ADV7103 treatment period)

  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

Study Arms (4)

ADV7103 1.5 mEq/Kg/day

ACTIVE COMPARATOR

Patients receive ADV7103 twice a day.

Drug: ADV7103

ADV7103 3.0 mEq/Kg/day

ACTIVE COMPARATOR

Patients receive ADV7103 twice a day.

Drug: ADV7103

ADV7103 4.5 mEq/Kg/day

ACTIVE COMPARATOR

Patients receive ADV7103 twice a day.

Drug: ADV7103

Placebo

PLACEBO COMPARATOR

Patients receive placebo twice a day.

Drug: Placebo

Interventions

Placebo DRUG

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.

Placebo

ADV7103 DRUG

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.

ADV7103 1.5 mEq/Kg/day; ADV7103 3.0 mEq/Kg/day; ADV7103 4.5 mEq/Kg/day

Eligibility Criteria

• Age: 6 Months - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• \. 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).
• \. 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).
• \. 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.
• \. 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.
• \. 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.
• \. 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.
• \. Patient or parents or legal representative(s) who has/have provided a signed written informed consent.
• \. Patient of ≤17 years of age for whom the assent has been collected or has been tried to be collected.
• \. 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.

You may not qualify if:

• \. Patient treated with the second line therapy and who cannot stop cystine chelating agents (sulfhydryl compounds) during the B12CS-B13CS study.
• \. 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).
• \. 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.
• \. 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.
• \. 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).
• \. Patient who is admitted to hospital in emergency settings. 11. Patient who participated in a clinical trial within the last 3 months before enrolment.
• \. Patient who is at risk of non-compliance in the judgment of the investigator.
• \. Patient who could present any other condition, which in the opinion of the investigator, would preclude participation in the study.
• \. Patient who cannot be contacted in case of emergency. 15. Patient under any administrative or legal supervision.

Sponsors & Collaborators

• Advicenne Pharma: lead

Study Sites (12)

Cliniques Universitaires Saint-Luc

Brussels, Brussels Capital, Belgium

Location

UZ Leuven, Gasthuisberg Hospital

Leuven, Leuven, Belgium

Location

CHU Grenoble

Grenoble, Grenoble Cedex, 38043, France

Location

CHRU Lille

Lille, Lille, 59000, France

Location

CHU Pitié-Salpétrière

Paris, Paris, 15013, France

Location

Hôpital Necker AP-HP

Paris, Paris, 75015, France

Location

Hôpital Necker Enfants Malades

Paris, Paris, 75015, France

Location

Hôpital Ténon - Explorations fonctionnelles Mutlidisciplinaires et INSERM UMR S 1155

Paris, Paris, 75020, France

Location

Hôpital Américain CHU de Reims

Reims, Reims, 51092, France

Location

CHU Reims

Reims, Reims, 51100, France

Location

CHU Purpan

Toulouse, Toulouse Cedex 9, 31059, France

Location

Centre Hospitalier Universitaire de Lyon - Hôpital Femme Mère Enfant

Bron, 69500, France

Location

Related Links

• Company website

MeSH Terms

Conditions

Cystinuria

Condition Hierarchy (Ancestors)

Renal Aminoacidurias; Renal Tubular Transport, Inborn Errors; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Luc-André Granier

  Advicenne Pharma

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 23, 2019
• First Posted: November 1, 2019
• Study Start: March 1, 2024
• Primary Completion: May 1, 2025
• Study Completion: June 1, 2025
• Last Updated: January 8, 2026

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

FR (10); BE (2)