Phase 2, Multicenter, Randomized, Open-label, Controlled, 2-arm Cross-over Study to Evaluate the Clinical Efficacy of a Renin Inhibitor, Aliskiren, Compared to an Angiotensin Converting Enzyme Inhibitor, Enalapril, in C3 Glomerulopathy

2019-001440-22

The aim of this cross-over trial 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 the angiotensin converting enzyme inhibitor, enalapril, in patients with the complement-mediated renal disease C3 glomerulopathy. Patients will be randomized to one or the other treatment for the first 6 months and then switch to the other treament for the following 2.5 years. Treatment will continue for altogether 3 years for each patient.

2020-10-01

2024-12-01

2024-12-01

Recruiting

Early phase I

30

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, angiotensin converting enzyme inhibitors, angiotensin receptor blockers or immune suppressive medications (such as mycophenolate mofetil/MMF or corticosteroids) 4. Written informed consent has been given by: 1. the patient's legal guardians if the patient is less than 15 years old 2. the patient and his/her legal guardians if the patient is ≥ 15 but \< 18 years old 3. the patient, if the patient is ≥ 18 years old 5. Female subjects of childbearing potential must: 1. Understand that the study medication is expected to have a teratogenic risk 2. Agree to use a highly effective contraceptive during study drug therapy. This applies unless the subject is less than 18 years of age, has not had sexual debut and commits to sexual abstinence confirmed by a pregnancy test on every study visit. Either of the following methods of contraception may be used: * Combined (estrogen and progesterone) hormonal contraception associated with inhibition of ovulation: oral, intravaginal or transdermal * Progestogen-only hormonal contraception associated with inhibition of ovulation: oral, injectable or implantable * Intrauterine device * Intrauterine hormone-releasing system * Bilateral tubal occlusion * Vasectomized partner * Sexual abstinence * Male or female condom with or without spermicide * Cap, diaphragm or sponge with spermicide 3. Agree to have a pregnancy test before the start of study medication. This requirement also applies to women of childbearing age who practice complete and continued abstinence and adolescent girls after menarche. 4. Agree to have a pregnancy test every 3rd month including at the end of study treatment, except in the case of confirmed tubal sterilization. This requirement also applies to women of childbearing age who practice complete and continued abstinence and adolescent girls after menarche. Exclusion Criteria: 1. Known allergy to aliskiren, ACEi or substances contained in these preparations. 2. Angioedema caused by aliskiren or enalapril 3. Weight \< 25 kg 4. Glomerular filtration rate ≤ 50 ml/min/1.73 m2 (measured by iohexol clearance) in children and ≤ 30 ml/min/1.73 m2 in adults. 5. Rapid deterioration of kidney function during the latest year of the disease 6. Patients with a renal transplant 7. Immune complex-mediated membranoproliferative glomerulonephritis (such as in HIV infection, hepatitis, SLE) 8. Females who breastfeed, are pregnant or planning to become pregnant during the study. 9. Co-morbidity such as malignancy, congestive heart failure, recent myocardial infarction. 10. Mental incapacity or language barriers to understand the contents of the study design. 11. Simultaneous use of another complement-antagonist (such as eculizumab). Eculizumab must be discontinued and complement activity normalized before the start of study drug. 12. Simultaneous use of aliskiren or enalapril with cyclosporine or nonsteroidal anti-inflammatory drugs (NSAID).

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2023-03-29