E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
hereditary kidney disease leading to progressive renal failure |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10001843 |
E.1.2 | Term | Alport's syndrome |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
|
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To investigate if the treatment of Alport's syndrome with the ACE inhibitor ramipril from early stages of disease is safe and significantly slows disease progression to renal failure. |
|
E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Definitive diagnosis of Alport syndrome: Kidney biopsy (patient or affected relative/s), and/or mutation analysis (hemizygous X-chromosomal or homozygous autosomal-recessive) and assessment of criteria for clinical diagnosis (haematuria, positive family history regarding kidney diseases, ocular changes, labyrinthine hearing loss)
- Alport syndrome levels 0, I or II at screening (microhaematuria without microalbuminuria or microalbuminuria [30-300 mg albumin/gCrea]) or proteinuria >300 mg albumin/gCrea with GFR>80ml/min). Patients with Alport stage II are not subject to randomization but are treated opel label.
- Aged between ≥24 months and <18 years at screening
- Assent from patient and informed consent from parents/legal guardian
|
|
E.4 | Principal exclusion criteria |
- Uncertain diagnosis or variants of Alport syndrome such as a heterozygous carrier
- Alport syndrome levels III, or IV (creatinine clearance <80 mL/min, or end stage renal failure [ESRF])
- Known allergies or intolerances to ramipril or related compounds
- Known contraindication for ACEi-therapy
- Additional chronic renal, pulmonary or cardiac diseases
- Pregnancy and lactation
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Primary Efficacy Endpoint: Time to progression of Alport Syndrome to the next disease level under ramipril treatment compared to placebo, for all randomised patients.
Primary Safety Endpoint: Incidence of adverse drug events (ADEs, e.g., angioedema, acute renal failure, hyperkalaemia) under ramipril treatment before disease progression compared to placebo before disease progression, for all randomised patients.
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Primary Efficacy Endpoint: within up to 6 years, until disease progression
Primary Safety Endpoint: within up to 6 years, until disease progression |
|
E.5.2 | Secondary end point(s) |
Secondary Efficacy Endpoint: Albuminuria after end of treatment corrected for baseline albuminuria for patients randomised to receive ramipril compared to placebo.
Secondary Safety Endpoint: Incidence of ADEs (e.g., angioedema, acute renal failure, hyperkalaemia) during treatment for patients randomised to receive ramipril compared to placebo.
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary Efficacy Endpoint: after up to 6 years
Secondary Safety Endpoint: after up to 6 years |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 15 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
Last follow-up visit, at 6 months after last study-specific dosing occasion or premature study termination. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 7 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 28 |