Study of Efficacy and Safety of Iptacopan in Participants With IC-MPGN

IC-MPGN Clinical Trial

— APPARENT  

Official title:

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 (IC-MPGN)

Clinical Trial Details — Status: Recruiting

Administrative data

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

Study information

• Verified date: May 2024
• Source: Novartis
• Contact: Novartis Pharmaceuticals
• Phone: 1-888-669-6682
• Email: novartis.email[@]novartis.com
• Is FDA regulated: No
• 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

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
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
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,  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)