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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05755386
Other study ID # CLNP023B12302
Secondary ID 2022-002328-11
Status Recruiting
Phase Phase 3
First received
Last updated
Start date October 2, 2023
Est. completion date November 26, 2026

Study information

Verified date June 2024
Source Novartis
Contact Novartis Pharmaceuticals
Phone 1-888-669-6682
Email novartis.email@novartis.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This study is designed as a multicenter, randomized, double-blind, parallel group, placebo-controlled study to evaluate the efficacy and safety of iptacopan (LNP023) in idiopathic immune complex mediated membranoproliferative glomerulonephritis.


Description:

The purpose of this Phase III study is to evaluate the efficacy and safety of iptacopan compared to placebo (both administered in combination with standard of care) in participants (adults and adolescents aged 12-17 years) with idiopathic IC-MPGN. The study aims to demonstrate a reduction in proteinuria and improvement in estimated glomerular filtration rate (eGFR) in participants treated with iptacopan compared to placebo. Change in patient-reported fatigue will also be evaluated. Alternative complement pathway (AP) dysregulation is believed to underlie the clinical manifestations and progression of IC-MPGN. Upon completion of study treatment, participants will have the option to discontinue iptacopan treatment and enter a 30 day safety follow-up or continue iptacopan treatment by transitioning to an open label extension study (CLNP023B12001B; NCT03955445) and continue iptacopan treatment.


Recruitment information / eligibility

Status Recruiting
Enrollment 68
Est. completion date November 26, 2026
Est. primary completion date October 23, 2026
Accepts healthy volunteers No
Gender All
Age group 12 Years to 60 Years
Eligibility Inclusion Criteria: - Male and female participants age = 12 and = 60 years at screening. - Diagnosis of idiopathic IC-MPGN as confirmed by kidney biopsy within 12 months prior to screening in adults and within 3 years of screening in adolescents (a biopsy report, review and confirmation by the Investigator is required). If such a biopsy is not available in an adult participant, this must be obtained at screening (performed and assessed locally for adults only). - Prior to randomization, all participants must have been on a maximally recommended or tolerated dose of renin angiotensin system inhibitors (RASi), e.g an ACEi or ARB for at least 90 days (or as according to local guidelines). The doses of other drugs administered to reduce proteinuria and control the disease including mycophenolic acids (MPAs - mycophenolate mofetil or mycophenolate sodium), corticosteroids, SGLT2 inhibitors and mineralocorticoid receptor antagonists should be stable for at least 90 days prior to randomization - UPCR = 1.0 g/g (= 113 mg/mmol) sampled from the first morning void urine sample at Day -75 and Day -15 - Estimated GFR (using the chronic kidney disease [CKD]-EPI formula for adult participants and modified Schwartz formula for adolescents aged 12 to 17 years) or measured GFR = 30 ml/min/1.73m2 at screening and Day -15. - Mandatory vaccination against Neisseria meningitidis and Streptococcus pneumoniae infection prior to the start of study treatment. If the participant has not been previously vaccinated, or if a booster is required, the vaccine should be given according to local regulations at least 2 weeks prior to the first administration of study treatment. If the study treatment has to start earlier than 2 weeks post vaccination, prophylactic antibiotic treatment should be initiated in accordance with local standard of care. - If not previously vaccinated, or if a booster is required, vaccination against Haemophilus influenzae infections should be given, if available and according to local regulations, at least 2 weeks prior to the first study treatment administration. If the study treatment has to start earlier than 2 weeks post vaccination, prophylactic antibiotic treatment should be initiated in accordance with local standard of care. Exclusion Criteria: - Participants who have undergone cell or solid organ transplantation, including kidney transplantation. - Participants diagnosed with secondary IC-MPGN including but not limited to any of the following conditions: - Deposition of antigen-antibody immune complexes as a result of any chronic infections, including - Hepatitis C virus (HCV) including HCV-associated mixed cryoglobulinemia, hepatitis B virus (HBV); - Bacterial-endocarditis, infected ventriculo-atrial shunt, visceral abscesses, leprosy, meningococcal meningitis; chronic bacterial infections - Protozoa/other infections- malaria, schistosomiasis, mycoplasma, leishmaniasis, filariasis, histroplasmosis Renal deposition of immune complexes as a result of a systemic autoimmune disease: - Systemic lupus erythematosus (SLE) - Sjögren syndrome - Rheumatoid arthritis - Mixed connective tissue disease Deposition of monoclonal immunoglobulins because of a monoclonal gammopathy due to plasma cell or B cell disorders. Monoclonal gammopathy of undetermined significance (MGUS) confirmed by the measurement of serum free light chains or other investigation as per local standard of care. Fibrillary glomerulonephritis - Rapidly progressive crescentic glomerulonephritis defined as a 50% decline in the eGFR within 3 months with kidney biopsy findings of glomerular crescent formation seen in at least 50% of glomeruli on the most recent biopsy. - Kidney biopsy showing interstitial fibrosis/tubular atrophy (IF/TA) of more than 50%. - Participants with an active systemic bacterial, viral or fungal infection within 14 days prior to study treatment administration or the presence of fever = 38°C (100.4°F) within 7 days prior to study treatment administration. - A history of recurrent invasive infections caused by encapsulated organisms, e.g., Neisseria meningitidis and Streptococcus pneumoniae. - The use of inhibitors of complement factors (e.g., Factor B, Factor D, complement 3 (C3) inhibitors, anti-Complement 5 (C5) antibodies, C5a receptor antagonists) within 6 months prior to the Screening visit. - The use of immunosuppressants (except MPAs), cyclophosphamide or systemic corticosteroids at a dose >7.5 mg/day (or equivalent for a similar corticosteroid medication) within 90 days of study drug administration. - The use of MPAs is not permitted within 90 days prior to randomization in India, as per the local health authority requirement. - Acute post-infectious glomerulonephritis at screening, based upon the opinion of the investigator. - Body mass index (BMI) >38 kg/m2 at screening and randomization. Body weight <35 kg at screening and randomization

Study Design


Related Conditions & MeSH terms

  • Glomerulonephritis, Membranoproliferative
  • IC-MPGN

Intervention

Drug:
Placebo
Placebo to iptacopan 200mg b.i.d. (Adults 200mg b.i.d; Adolescents 2x 100mg b.i.d)
iptacopan
iptacopan 200 mg b.i.d. (Adults 200mg b.i.d; Adolescents 2x 100mg b.i.d)

Locations

Country Name City State
Argentina Novartis Investigative Site Caba Buenos Aires
Brazil Novartis Investigative Site Belo Horizonte MG
Brazil Novartis Investigative Site Botucatu SP
Brazil Novartis Investigative Site Brasilia DF
Brazil Novartis Investigative Site Niteroi RJ
Brazil Novartis Investigative Site Pernambuco Recife
Brazil Novartis Investigative Site Porto Alegre RS
Brazil Novartis Investigative Site Rio de Janeiro RJ
Brazil Novartis Investigative Site Salvador
Brazil Novartis Investigative Site Santo Andre SP
Brazil Novartis Investigative Site Sao Paulo SP
Brazil Novartis Investigative Site São Paulo SP
Canada Novartis Investigative Site Montreal Quebec
Czechia Novartis Investigative Site Prague 2
France Novartis Investigative Site Montpellier
France Novartis Investigative Site Paris
France Novartis Investigative Site Paris 15
France Novartis Investigative Site Toulouse 4
Germany Novartis Investigative Site Berlin
Germany Novartis Investigative Site Dresden
Germany Novartis Investigative Site Essen
Germany Novartis Investigative Site Mainz
India Novartis Investigative Site Nagpur Maharashtra
India Novartis Investigative Site New Delhi
Israel Novartis Investigative Site Haifa
Israel Novartis Investigative Site Jerusalem
Israel Novartis Investigative Site Petach Tikva
Italy Novartis Investigative Site Bari BA
Italy Novartis Investigative Site Milano MI
Italy Novartis Investigative Site Napoli
Italy Novartis Investigative Site Ranica BG
Italy Novartis Investigative Site Roma RM
Italy Novartis Investigative Site Torino TO
Japan Novartis Investigative Site Hachioji-city Tokyo
Japan Novartis Investigative Site Okayama-city Okayama
Poland Novartis Investigative Site Olsztyn
Poland Novartis Investigative Site Warszawa
Poland Novartis Investigative Site Warszawa
Poland Novartis Investigative Site Wroclaw
Spain Novartis Investigative Site Barcelona Catalunya
Spain Novartis Investigative Site Madrid
Spain Novartis Investigative Site Madrid
Spain Novartis Investigative Site Pamplona Navarra
Spain Novartis Investigative Site Salamanca Castilla Y Leon
Switzerland Novartis Investigative Site Bern
Switzerland Novartis Investigative Site Lausanne
Turkey Novartis Investigative Site Ankara
Turkey Novartis Investigative Site Izmir
Turkey Novartis Investigative Site Kocaeli
United Kingdom Novartis Investigative Site Belfast
United Kingdom Novartis Investigative Site Cardiff
United States Childrens Hospital Colorado Aurora Colorado
United States Massachusetts General Hospital Nephrology Department Boston Massachusetts
United States Ronald Reagan UCLA Medical Center UCLA Connie Frank Clinic Los Angeles California
United States University of Minnesota Renal Disease and Hypertension Minneapolis Minnesota
United States Col Uni Med Center New York Presby New York New York
United States Univ Cali Irvine ALS Neuromuscular Tustin Orange California
United States UCSF Main Centre San Francisco California
United States Baylor Scott and White Research . Temple Texas
Vietnam Novartis Investigative Site Ho Chi Minh

Sponsors (1)

Lead Sponsor Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Vietnam,  Argentina,  Brazil,  Canada,  Czechia,  France,  Germany,  India,  Israel,  Italy,  Japan,  Poland,  Spain,  Switzerland,  Turkey,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary Log-transformed ratio to baseline in UPCR (sampled from a 24-hour urine collection) at 6 months. To demonstrate the superiority of iptacopan compared to placebo in reducing proteinuria at 6 months. 6 months (double-blind)
Primary Log-transformed ratio to baseline in UPCR at the 12-month visit (both study treatment arms) To evaluate the effect of iptacopan on proteinuria at 12 months. 12 months
Primary Log-transformed ratio to 6-month visit in UPCR at the 12-month visit in the placebo arm. To evaluate the effect of iptacopan on proteinuria at 12 months. 12 months
Secondary Change from baseline in eGFR To demonstrate the superiority of iptacopan vs. placebo in improving estimated glomerular filtration rate (eGFR). 6 months of double-blind & 6 months of open label (up to 12 months)
Secondary Change in eGFR from the 6-month visit to the 12- month visit of the placebo arm To evaluate the effect at 12 months of iptacopan in improving eGFR month 6 and month 12
Secondary Proportion of patients achieved a composite renal endpoint To demonstrate the superiority of iptacopan vs. placebo in the proportion of participant who achieved a composite renal endpoint at 6 and 12 months (both study arms). 6 months of double-blind & 6 months of open label (up to 12 months)
Secondary Proportion of patients achieving a composite renal endpoint from the 6-month visit to the 12-month visit of the placebo arm To evaluate the effect at 12 months of iptacopan on a composite renal endpoint in placebo arm month 6, month 12
Secondary Change from baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) score. To demonstrate the superiority of iptacopan compared to placebo in improvement of patient-reported fatigue at 6 months and 12 months (both study arms). 6 months of double-blind & 6 months of open label (up to 12 months)
Secondary Change in the FACIT-Fatigue score from the 6-month visit to the 12-month visit at the placebo arm To evaluate the effect at 12 months of iptacopan in improvement of participant-reported fatigue in placebo arm month 6, month 12
Secondary Number of participants with abnormal vital signs, ECGs and safety laboratory measurements To evaluate the safety and tolerability of iptacopan compared to placebo, number of participants with abnormal vital signs (msDBP/msSBP/heart rate), ECGs and safety laboratory measurements will be collected.
msDBP: mean sitting diastolic blood pressure msSBP: mean sitting systolic blood pressure
6 months of double-blind & 6 months of open label (up to 12 months)
Secondary Number of participants with study drug discontinuation due to an AE To evaluate the safety and tolerability of iptacopan compared to placebo, number of participants with study drug discontinuation due to an AE (or any safety issue) will be collected 6 months of double-blind & 6 months of open label (up to 12 months)
Secondary Number of participants with clinically significant changes in heart rate, blood pressure, echocardiography parameters and NT-proBPN in adolescent patients To evaluate the effect of iptacopan compared to placebo, number of participants with clinically significant changes in heart rate, blood pressure (msDBP/ msSBP), echocardiography parameters and NT-proBPN in adolescent patients will be collected 6 months of double-blind & 6 months of open label (up to 12 months)
See also
  Status Clinical Trial Phase
Active, not recruiting NCT05067127 - Phase III Study Assessing the Efficacy and Safety of Pegcetacoplan in Patients With C3 Glomerulopathy or Immune-Complex Membranoproliferative Glomerulonephritis Phase 3
Active, not recruiting NCT05809531 - An Open-Label, Nonrandomized, Multicenter Extension Study to Evaluate the Long-term Safety and Efficacy of Pegcetacoplan in Participants With C3 Glomerulopathy or Immune-Complex Membranoproliferative Glomerulonephritis Phase 3
Terminated NCT03459443 - A Proof of Concept Study for a 12 Month Treatment in Patients With C3G or IC-MPGN Treated With ACH-0144471 Phase 2
Active, not recruiting NCT04572854 - Study Assessing the Safety and Efficacy of Pegcetacoplan in Post-Transplant Recurrence of C3G or IC-MPGN Phase 2
Completed NCT03723512 - Non-contrast Enhanced MRI in Patients With C3 Glomerulopathy (C3G) or Immune-complex Membranoproliferative Glomerulonephritis (IC-MPGN) Enrolled in the ACH471-205 Study N/A
Available NCT04729062 - C3G/Primary IC-MPGN EAP