Comparing Aliskiren and Enalapril for C3 Glomerulopathy Treatment

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

This study is testing whether a new kidney treatment called aliskiren works better than the standard treatment enalapril for people with C3 glomerulopathy.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 6 Years and up
• Sex: All
• Sponsor: Region Skane (other)
• Drugs / interventions: eculizumab
• Locations: 4 sites (Gothenburg and 3 other locations)
• Trial ID: NCT04183101 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effectiveness of aliskiren, a direct renin inhibitor, in treating C3 glomerulopathy compared to enalapril, an angiotensin converting enzyme inhibitor. Patients will be randomized to receive either treatment for the first 6 months, followed by a switch to the other treatment for an additional 2.5 years. The primary goal is to assess the impact of aliskiren on complement activation and kidney function, with secondary objectives including the evaluation of proteinuria and blood pressure. The study aims to include a maximum of 30 patients, with careful monitoring of their renal function throughout the trial.

Who should consider this trial

Good fit: Ideal candidates include children aged 6 and older and adults diagnosed with C3 glomerulopathy or Dense Deposit Disease, with adequate renal function.

Not a fit: Patients with severe renal failure or those not meeting the specific inclusion criteria will not benefit from this study.

Why it matters

Potential benefit: If successful, this trial could provide a new treatment option that may improve kidney function and reduce disease progression in patients with C3 glomerulopathy.

How similar studies have performed: While this approach is novel in the context of C3 glomerulopathy, similar studies evaluating renin inhibitors have shown promise in other renal conditions.

Eligibility criteria

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).

Where this trial is running

Gothenburg and 3 other locations

• Sahlgrenska Hospital — Gothenburg, Sweden (NOT_YET_RECRUITING)
• Region Skåne Skåne Universitetssjukhus — Lund, Sweden (RECRUITING)
• Karolinska Hospital — Stockholm, Sweden (NOT_YET_RECRUITING)
• Akademiska sjukhuset — Uppsala, Sweden (NOT_YET_RECRUITING)

Study contacts

• Principal investigator: Diana Karpman — Region Skane
• Study coordinator: Diana Karpman, MD PhD

Conditions: C3 Glomerulopathy, Membranoproliferative Glomerulonephritis, Complement Abnormality, Dense Deposit Disease, C3 Glomerulonephritis