Controlled clinical trial to evaluate the clinical efficacy and safety of a drug that inhibits renin, aliskiren, compared to an angiotensin converting enzyme inhibitor enalapril in children and adults with the kidney disease C3 glomerulopathy

INTERVENTION: Trade Name: aliskiren generic rasilez trade name Pharmaceutical Form: Tablet Trade Name: enalapril generic Renitec trade name Product Name: enalapril Pharmaceutical Form: Tablet CONDITION: C3 glomerulopathy Therapeutic area: Diseases [C] ‐ Immune System Diseases [C20] PRIMARY OUTCOME: ; Main Objective: The aim of this project is to assess aliskiren, a direct renin inhibitor, as a novel treatment to block complement activation in the kidneys and thereby attenuate renal disease and stabilize or improve kidney function and compare it to the currently used treatment with an angiotensin converting enzyme inhibitor (ACEi) in patients with the complement‐mediated renal disease C3 glomerulopathy.; The primary objective is to assess the effect and safety of aliskiren on reducing systemic and local complement activation as indicated by a reduction of serum C3 during a cross‐over study and serum C3 and complement deposition in renal biopsies during an extension study in patients with C3 glomerulopathy as compared to the currently used treatment with enalapril (ACEi).; ; Primary end point(s): The primary end‐point assays include:; Blood samples related to complement activation: C3.; ; Renal biopsies: complement deposition.; ; Timepoint(s) of evaluation of this end point: Start and every 3rd month for 3 years: C3 in blood samples.; ; Kidney biopsy: within 2 years of start and within 3 years of the start of the trial or at the end.; Secondary Objective: To assess the effect of aliskiren as compared to the currently used treatment with ACEi enalapril on: complement activation (such as serum C3a, C3dg, C5a and related complement assays), proteinuria, kidney function, kidney biopsy findings, blood pressure, activation of the renin angiotensin system. SECONDARY OUTCOME: ; Secondary end point(s): Physical examination, blood samples related to complement activation: C3dg, C3a, C5a, C5, TCC, C3 nephritic factor and related complement assays. Albumin level.; ; Urine samples: urine dipstick, albumin/creatinine ratio, angiotensinogen; ; Kidney function with iohexol clearance; ; Kidney biopsy: within 2 years of start and within the 3 years of the trial or at the end.; ; Timepoint(s) of evaluation of this end point: Start and every 3rd month for 3 years: Physical examination, blood samples related to complement activation: C3dg, C3a, C5a, C5, TCC, C3 nephritic factor and related complement assays. Albumin level.; ; Urine samples: urine dipstick, albumin/creatinine ratio, angiotensinogen; ; Start and every 12 months: kidney function with iohexol clearance; ; Kidney biopsy: within 2 years of start and within the 3 years of the trial or at the end.; INCLUSION CRITERIA: 1. Children = 6 years and adults. 2. Initial diagnosis of Dense Deposit Disease and C3 glomerulonephritis confirmed by kidney biopsy obtained not more than 2 years before the first dose of the study drug. 3. Either absence of treatment at the study start or ongoing treatment with aliskiren, ACEi, ARBs or immune suppressive medications (such as mycophenolate mofetil/MMF or corticosteroids) 4. Written informed consent has been given by: a. the patient’s legal guardians if the patient is less than 15 years old b. the patient and his/her legal guardians if the patient is = 15 but < 18years old c. the patient if the patient is = 18 years old 5. Female subjects of childbearing potential must: a. Understand that the study medication is expected to have a teratogenic risk b. Agree