Study Evaluating Patients With Cystinuria

NCT04137978 | Withdrawn Phase 2

• 1 other identifier: B14CS
• Study Type: interventional
• Target: N/A
• Locations: 2 countries
• Sites: 13

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.

Conditions

Cystinuria

Outcome Measures

Primary Outcomes (1)

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

  To evaluate the safety and the tolerability of ADV7103 and standard of care (SoC) after a long-term treatment.

  7 Days

Study Arms (2)

ADV7103

ACTIVE COMPARATOR

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

Standard of care comparator

ACTIVE COMPARATOR

Alkalinising treatment (SoC) taken at the usual dose and frequency

Drug: Standard of Care

Interventions

ADV7103 DRUG

Patients receive ADV7103 twice a day at optimal dose.

Also known as: Potassium Citrate and Potassium Bicarbonate

ADV7103

Standard of Care DRUG

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.

Standard of care comparator

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:

• For ADV7103 cohort:
• Patient who has participated to and completed the previous B12CS Study or B13CS Study.
• Patient for whom the safety and tolerability of ADV7103 were satisfactory during B12CS Study or B13CS Study.
• 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 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.
• For Standard of Care cohort:
• 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).
• 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 male or female, including child aged between 6 months and 17 years old and adult aged ≥ 18 years old up to 70 years old.
• 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:

• For ADV7103 cohort:
• Patient who has not participated to B12CS study or B13CS study
• Patient for whom any safety issue could contraindicate her/his participation to the extension study
• For Standard of Care cohort:
• Patient that is receiving the second line therapy -- cystine chelating agents (sulfhydryl compounds).
• Patient who presents kalaemia \> 5.0 mmol/L.
• 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.
• 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 is admitted to hospital in emergency settings.
• 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.

Sponsors & Collaborators

• Advicenne Pharma: lead

Study Sites (13)

Cliniques Universitaires Saint-Luc

Brussels, Belgium

Location

UZ Leuven, Gasthuisberg Hospital

Leuven, Belgium

Location

CHU de Bordeaux - Hôpital Pellegrin

Bordeaux, 33076, France

Location

Centre Hospitalier Universitaire de Lyon

Bron, 69500, France

Location

CHU Grenoble

Grenoble, 38043, France

Location

CHRU Lille

Lille, 59000, France

Location

CHU Pitié-Salpétrière

Paris, 15013, France

Location

Hôpital Necker AP-HP

Paris, 75015, France

Location

Hôpital Necker Enfants Malades

Paris, 75015, France

Location

Hôpital Ténon - Explorations fonctionnelles Mutlidisciplinaires et INSERM UMR S 1155

Paris, 75020, France

Location

Hôpital Américain CHU de Reims

Reims, 51092, France

Location

CHU Reims

Reims, 51100, France

Location

CHU Purpan

Toulouse, 31059, France

Location

Related Links

• Company website

MeSH Terms

Conditions

Cystinuria

Interventions

Potassium Citrate; potassium bicarbonate; Standard of Care

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

Intervention Hierarchy (Ancestors)

Citric Acid; Citrates; Tricarboxylic Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Luc-André Granier, M.D.

  Advicenne Pharma

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2019
• First Posted: October 24, 2019
• Study Start: May 1, 2024
• Primary Completion: June 1, 2025
• Study Completion: August 1, 2025
• Last Updated: March 12, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (11); BE (2)