This is a phase III, multi-centre, randomised, placebo-controlled, patient and investigator-blind study in paediatric patients with early stages of Alport syndrome to assess the safety and efficacy of the ACEi ramipril in slowing disease progression.

Alport syndrome stages that describe the extent of renal damage and loss of function are defined as:

• 0 Microhaematuria without microalbuminuria (usually at birth)
• I Microalbuminuria (30-300 mg albumin/gCrea)
• II Proteinuria >300 mg albumin/gCrea
• III > 25% decline of normal renal function (creatinine clearance)
• IV End stage renal failure (ESRF)

Eligible patients with Alport stages 0 and I will be randomly assigned at a 2:1 ratio to receive once daily ramipril or placebo. In addition, Alport stage II patients may be treated open Label. Eligible patients who, or whose parents/legal guardian refuse randomisation after eligibility is confirmed, and patients who have been treated with ramipril prior to the study, may be treated open-label with ramipril as per protocol. The total number of patients will not exceed 120, with the number of randomised patients not exceeding 60, and the number of patients treated open label from Day 1 of the study aimed to be approximately 60.

Randomised patients whose disease progresses to the next disease level during the 3 year treatment period will be unblinded, and open label ramipril treatment will be initiated and continued, respectively, depending on prior treatment randomisation.

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

Exclusion Criteria:

• Uncertain diagnosis or variants of Alport syndrome such as a heterozygous carrier
• Alport syndrome levels III, or IV (albuminuria >300 mg/g Crea, creatinine clearance <60 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