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C3 GlomerulopathyPhase 2NCT04183101

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

A Phase 2 study testing Aliskiren and Enalapril in people with C3 Glomerulopathy and Membranoproliferative Glomerulonephritis, run by Region Skane at 4 sites in Sweden.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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… Read more about this study

Who is it for?
Ages 6 years and older
What is being tested?
Aliskiren and Enalapril
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
4 sitesSweden
Study dates
1 Oct 2020to Dec 2029
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 6 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • Vasectomized partner
  • Sexual abstinence
  • Male or female condom with or without spermicide
  • Cap, diaphragm or sponge with spermicide
  • 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.
  • 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.

Who cannot join

  • 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
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  • 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).

Trial locations and contacts

4 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Diana Karpman, MD PhD contact

+46-46-2220747

diana.karpman@med.lu.se

Zivile Bekassy, MD PhD contact

zivile.bekassy@med.lu.se

Sweden4 sites, 4 recruiting
  • Sahlgrenska Hospital

    Gothenburg

    Gregor Guron, MD PhD, gregor.guron@vgregion.se

    Not yet recruiting
  • Region Skåne Skåne Universitetssjukhus

    Lund, 22184

    Diana Karpman, MD PhD, +46462220747, diana.karpman@med.lu.se

    Zivile Bekassy, MD PhD, zivile.bekassy@med.lu.se

    Recruiting
  • Karolinska Hospital

    Stockholm

    Peter Barany, MD PhD, peter.barany@sll.se

    Not yet recruiting
  • Akademiska sjukhuset

    Uppsala

    Hans Furuland, MD PhD, +4618-6110000 ext. 14052, hans.furuland@medsci.uu.se

    Not yet recruiting

Other trials in Sweden

About this study

Official title: 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

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.

Read the detailed description

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 the cross-over study and serum C3 and complement deposition in renal biopsies during the extension study in patients with C3 glomerulopathy as compared to the currently used treatment with the angiotensin converting enzyme inhibitor (ACEi) enalapril.

Secondary objectives are to assess the effect of aliskiren as compared to the currently used treatment with the 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.

Aliskiren will be administered orally in tablet form at 150 -300 mg/daily (maximal dose 300 mg). Enalapril 2.5-20 mg/daily (maximal dose 20 mg). These drugs may be administered once or twice.

The investigators estimate an inclusion of maximum 15 patients for start of treatment with aliskiren and maximum 15 patients for start of treatment with enalapril. Suitable patients will be chosen from those patients who:

  1. Do not have severe renal failure. Pediatric patients will be included if they have a glomerular filtration rate ≥ 50 ml/min/1.73m2, adults ≥ 30 ml/min/1.73m2.
  2. Children, above the age of 6 years of age and adults.
  3. Patients treated with aliskiren will be compared to patients treated with the ACE inhibitor enalapril as monotherapy. Use of ACE inhibitor as a nephroprotective therapy will increase renin levels without blocking its effect. Thus, the investigators will compare patients on aliskiren with those on enalapril to investigate if ACE inhibition as monotherapy has a negative effect on complement activation in comparison to direct renin inhibition.
  4. Patients treated with immune suppressive medications at the start (such as mycophenolate mofetil (MMF) or corticosteroids) will be compared to patients treated with MMF or steroids plus aliskiren or enalapril.

All suitable patients who fulfill inclusion criteria and who submitted written informed consent (patient or patient's legal guardians) will have undergone a renal biopsy at the most 2 years before inclusion or at inclusion and will be randomized for treatment with aliskiren or enalapril. After 6 months patients on aliskiren will switch to enalapril and vice versa, patients on enalapril will switch to aliskiren treatment. Patients will be followed routinely, every 3rd month, regarding renal function (creatinine, urea, estimated glomerular filtration rate), albumin (blood and urine), renin levels and complement activation assays in blood samples (C3, C3dg, C5, properdin, soluble terminal complement complex, C3a, C5a, C3 nephritic factor and other complement assays). The follow-up period, a total of 3 years from the start, will be carried out by the patient's own nephrologist and will not differ from the clinical follow-up offered patients not participating in the study. After 1-3 years (when medically indicated but at the most 3 years after start), a repeat renal biopsy will be performed to validate the effect of treatment on renal morphology. Renal biopsies, both the initial and the repeat biopsy, will be evaluated for complement deposition and glomerular basement membrane thickness.

Being tested
Aliskiren, Enalapril
Medical subject headings
Glomerulonephritis, Membranoproliferative

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AliskirenDrug

    Also called Enalapril

    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.

  • EnalaprilDrug

    Also called Aliskiren

    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.

Study groups in NCT04183101
Study groupRoleWhat they receive
Aliskiren treatmentExperimentalPatients 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.
Receives: Drug: Aliskiren
Enalapril treatmentActive comparatorPatients 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.
Receives: Drug: Enalapril

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 3 years

  2. Complement deposition in kidneys

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

    Measured: 3 years

Secondary outcomes (5)
  1. C3a in serum

    To assess the effect of aliskiren compared to currently used treatment with the ACEi enalapril on C3a in serum

    Measured: 3 years

  2. C3dg in plasma

    To assess the effect of aliskiren compared to currently used treatment with the ACEi enalapril on C3dg in plasma

    Measured: 3 years

  3. C5a in serum

    To assess the effect of aliskiren compared to currently used treatment with the ACEi enalapril on C5a in serum

    Measured: 3 years

  4. Glomerular basement membrane thickness

    To assess the effect of aliskiren compared to currently used treatment with the ACEi enalapril on glomerular basement membrane thickness assessed by electron microscopy measurement

    Measured: 3 years

  5. Proteinuria

    To assess the effect of aliskiren compared to currently used treatment with the ACEi enalapril on protein levels in urine measured as the ratio between albumin/creatinine in urine

    Measured: 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Dec 2019
  2. Study start1 Oct 2020
  3. Primary completionDec 2029 (estimated)
  4. Study completionDec 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Model description
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
Masking
None (open label)
Enrolment
30 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04183101
Sponsor's protocol ID
2019-001440-22
Other IDs
2019-001440-22, 2019
Status last verified
Jun 2025
First submitted
14 Nov 2019
Last updated
22 Jun 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: The study and de-identified data will be shared with study coordinators at various sites

Publications

  • 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.

    PubMed 29884545
  • 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.

    PubMed 30692664
  • 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.

    PubMed 10792600

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Aliskiren and Enalapril in people with C3 Glomerulopathy and Membranoproliferative Glomerulonephritis, run by Region Skane at 4 sites in Sweden.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 22 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Diana Karpman, MD PhD (+46-46-2220747, diana.karpman@med.lu.se), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

C3 levels in serum (time frame: 3 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04183101, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jun 2025.

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