Evaluation of a Renin Inhibitor, Aliskiren, Compared to Enalapril, in C3 Glomerulopathy

NCT04183101 | Recruiting Phase 2 DMC

• 1 other identifier: 2019-001440-22
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

C3 Glomerulopathy; Membranoproliferative Glomerulonephritis; Complement Abnormality; Dense Deposit Disease; C3 Glomerulonephritis

Outcome Measures

Primary Outcomes (2)

• C3 levels in serum

  To assess the effect and safety of aliskiren as compared to enalapril on reducing systemic complement activation as assayed by C3 levels in serum.

  3 years

• Complement deposition in kidneys

  To quantify complement deposition in kidney biopsies from patients with C3 glomerulopathy using immunohistological staining

  3 years

Secondary Outcomes (5)

• C3a in serum

  3 years

• C3dg in plasma

  3 years

• C5a in serum

  3 years

• Glomerular basement membrane thickness

  3 years

• Proteinuria

  3 years

Other Outcomes (1)

• Renal function

  3 years

Study Arms (2)

Aliskiren treatment

EXPERIMENTAL

Patients will be randomized to tablet treatment with aliskiren (target daily dose) 150-300 mg once daily or every other day (depending on weight) for 6 months. After 6 months the patients will be switched to tablet treatment with enalapril (target daily dose 7.5-20 mg once or twice a day) for the coming 2,5 years.

Drug: Aliskiren

Enalapril treatment

ACTIVE COMPARATOR

Patients will be randomized to tablet treatment with enalapril (target daily dose 7.5-20 mg once or twice a day) for 6 months. After 6 months the patients will be switched to tablet treatment with aliskiren (target daily dose) 150-300 mg once daily or every other day (depending on weight) for the coming 2,5 years.

Drug: Enalapril

Interventions

Aliskiren DRUG

Patients will be randomized to start treatment with aliskiren tablet 150 mg every other day up to 300 mg daily depending on weight. After 6 months switch to enalapril 2.5-20 mg daily and continue with that 2.5 years.

Also known as: Enalapril

Aliskiren treatment

Enalapril DRUG

Patients will be randomized to start with enalapril 2.5-20 mg daily depending on weight. After 6 months switch to aliskiren tablet 150 mg every other day up to 300 mg daily depending on weight and continue with this treatment for 2.5 years.

Also known as: Aliskiren

Enalapril treatment

Eligibility Criteria

• Age: 6 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Children ≥ 6 years and adults.
• 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.
• 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)
• Written informed consent has been given by:
• the patient's legal guardians if the patient is less than 15 years old
• the patient and his/her legal guardians if the patient is ≥ 15 but \< 18 years old
• the patient, if the patient is ≥ 18 years old
• Female subjects of childbearing potential must:
• Understand that the study medication is expected to have a teratogenic risk
• 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

You may not qualify if:

• Known allergy to aliskiren, ACEi or substances contained in these preparations.
• Angioedema caused by aliskiren or enalapril
• Weight \< 25 kg
• Glomerular filtration rate ≤ 50 ml/min/1.73 m2 (measured by iohexol clearance) in children and ≤ 30 ml/min/1.73 m2 in adults.
• Rapid deterioration of kidney function during the latest year of the disease
• Patients with a renal transplant
• Immune complex-mediated membranoproliferative glomerulonephritis (such as in HIV infection, hepatitis, SLE)
• Females who breastfeed, are pregnant or planning to become pregnant during the study.
• Co-morbidity such as malignancy, congestive heart failure, recent myocardial infarction.
• Mental incapacity or language barriers to understand the contents of the study design.
• Simultaneous use of another complement-antagonist (such as eculizumab). Eculizumab must be discontinued and complement activity normalized before the start of study drug.
• Simultaneous use of aliskiren or enalapril with cyclosporine or nonsteroidal anti-inflammatory drugs (NSAID).

Sponsors & Collaborators

• Region Skane: lead

Study Sites (4)

Sahlgrenska Hospital

Gothenburg, Sweden

NOT YET RECRUITING

Region Skåne Skåne Universitetssjukhus

Lund, 22184, Sweden

RECRUITING

Karolinska Hospital

Stockholm, Sweden

NOT YET RECRUITING

Akademiska sjukhuset

Uppsala, Sweden

NOT YET RECRUITING

Related Publications (3)

• Bekassy ZD, Kristoffersson AC, Rebetz J, Tati R, Olin AI, Karpman D. Aliskiren inhibits renin-mediated complement activation. Kidney Int. 2018 Oct;94(4):689-700. doi: 10.1016/j.kint.2018.04.004. Epub 2018 Jun 5.

  PMID: 29884545 BACKGROUND

• Smith RJH, Appel GB, Blom AM, Cook HT, D'Agati VD, Fakhouri F, Fremeaux-Bacchi V, Jozsi M, Kavanagh D, Lambris JD, Noris M, Pickering MC, Remuzzi G, de Cordoba SR, Sethi S, Van der Vlag J, Zipfel PF, Nester CM. C3 glomerulopathy - understanding a rare complement-driven renal disease. Nat Rev Nephrol. 2019 Mar;15(3):129-143. doi: 10.1038/s41581-018-0107-2.

  PMID: 30692664 BACKGROUND

• Taal MW, Brenner BM. Renoprotective benefits of RAS inhibition: from ACEI to angiotensin II antagonists. Kidney Int. 2000 May;57(5):1803-17. doi: 10.1046/j.1523-1755.2000.00031.x.

  PMID: 10792600 BACKGROUND

MeSH Terms

Conditions

Glomerulonephritis, Membranoproliferative

Interventions

aliskiren; Enalapril

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Dipeptides; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Diana Karpman

  Region Skåne

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Diana Karpman, MD PhD

CONTACT

+46-46-2220747; diana.karpman@med.lu.se

Zivile Bekassy, MD PhD

CONTACT

zivile.bekassy@med.lu.se

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase 2, multicenter, randomized, open-label, controlled, 2-arm cross-over study to evaluate the clinical efficacy and safety of a renin inhibitor, aliskiren, compared to an angiotensin converting enzyme inhibitor, enalapril, in children and adults with C3 glomerulopathy

Study Record Dates

• First Submitted: November 14, 2019
• First Posted: December 3, 2019
• Study Start: October 1, 2020
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2029
• Last Updated: June 22, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: 5 years from the start, two years of inclusion until the inclusion of the last patient
• Access Criteria: Data will be presented at meetings and by de-identified emails

Locations

SE (4)