Study Evaluating Patients With Cystinuria

• ClinicalTrials.gov Identifier: NCT04137978
• Recruitment Status: Unknown
• First Posted: October 24, 2019
• Last Update Posted: October 24, 2019
• Sponsor: Advicenne Pharma
• Information provided by (Responsible Party): Advicenne Pharma

Study Description

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.

Study Design

• 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

Arms and Interventions

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.

Outcome Measures

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.

Eligibility Criteria

• 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.

Contacts and Locations

Locations

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

• Study Director: Luc-André Granier, M.D.; Advicenne Pharma

More Information

Additional Information:

Company website 

• Responsible Party: Advicenne Pharma
• ClinicalTrials.gov Identifier: NCT04137978
• Other Study ID Numbers: B14CS
• First Posted: October 24, 2019
• Last Update Posted: October 24, 2019
• Last Verified: October 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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:

Cystinuria; Renal Aminoacidurias; Renal Tubular Transport, Inborn Errors; Kidney Diseases; Urologic Diseases; Genetic Diseases, Inborn; Potassium Citrate; Diuretics; Natriuretic Agents; Physiological Effects of Drugs; Expectorants; Respiratory System Agents