Last Update: Jun 11, 2024
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)
ClinicalTrials.gov Identifier:
Novartis Reference Number:CLNP023B12302
All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation.

Study Description

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. 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.

IC-MPGN
Phase3
Recruiting
68
Oct 02, 2023
Nov 26, 2026
All
12 Years - 60 Years (Child, Adult)

Interventions

Drug

iptacopan

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

Placebo

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

Eligibility Criteria

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 Location

Novartis Investigative Site

Recruiting

Caba,Buenos Aires,C1425agc,Argentina

Novartis Investigative Site

Recruiting

Brasilia,DF,71635-580,Brazil

Novartis Investigative Site

Recruiting

Rio de Janeiro,RJ,22211 230,Brazil

Novartis Investigative Site

Recruiting

Pernambuco,Recife,50740-900,Brazil

Novartis Investigative Site

Recruiting

Niteroi,RJ,24020 096,Brazil

Novartis Investigative Site

Recruiting

Belo Horizonte,MG,30150-221,Brazil

Novartis Investigative Site

Recruiting

Salvador,40301-155,Brazil

Novartis Investigative Site

Recruiting

Porto Alegre,RS,90020-090,Brazil

Novartis Investigative Site

Recruiting

Santo Andre,SP,09090-790,Brazil

Novartis Investigative Site

Recruiting

São Paulo,SP,04038-002,Brazil

Novartis Investigative Site

Recruiting

Botucatu,SP,18618-970,Brazil

Novartis Investigative Site

Recruiting

Sao Paulo,SP,05403 000,Brazil

Novartis Investigative Site

Recruiting

Montreal,Quebec,H3t 1c5,Canada

Novartis Investigative Site

Recruiting

Prague 2,128 08,Czechia

Novartis Investigative Site

Recruiting

Paris 15,75015,France

Novartis Investigative Site

Recruiting

Toulouse 4,31054,France

Novartis Investigative Site

Recruiting

Montpellier,34295,France

Novartis Investigative Site

Recruiting

Mainz,55131,Germany

Novartis Investigative Site

Recruiting

Dresden,01307,Germany

Novartis Investigative Site

Recruiting

Berlin,13353,Germany

Novartis Investigative Site

Recruiting

Essen,45147,Germany

Novartis Investigative Site

Recruiting

New Delhi,110029,India

Novartis Investigative Site

Recruiting

Nagpur,Maharashtra,440015,India

Novartis Investigative Site

Recruiting

Petach Tikva,49202,Israel

Novartis Investigative Site

Recruiting

Jerusalem,91031,Israel

Novartis Investigative Site

Recruiting

Haifa,310 9601,Israel

Novartis Investigative Site

Recruiting

Bari,BA,70124,Italy

Novartis Investigative Site

Recruiting

Torino,TO,10126,Italy

Novartis Investigative Site

Recruiting

Roma,RM,00165,Italy

Novartis Investigative Site

Recruiting

Milano,MI,20122,Italy

Novartis Investigative Site

Recruiting

Ranica,BG,24020,Italy

Novartis Investigative Site

Recruiting

Napoli,80100,Italy

Novartis Investigative Site

Recruiting

Okayama-city,Okayama,700-8558,Japan

Novartis Investigative Site

Recruiting

Hachioji-city,Tokyo,193-0944,Japan

Novartis Investigative Site

Recruiting

Warszawa,02-006,Poland

Novartis Investigative Site

Recruiting

Warszawa,02097,Poland

Novartis Investigative Site

Recruiting

Olsztyn,10-561,Poland

Novartis Investigative Site

Recruiting

Wroclaw,50-417,Poland

Novartis Investigative Site

Recruiting

Madrid,280796,Spain

Novartis Investigative Site

Recruiting

Salamanca,Castilla Y Leon,37007,Spain

Novartis Investigative Site

Recruiting

Pamplona,Navarra,31008,Spain

Novartis Investigative Site

Recruiting

Madrid,28040,Spain

Novartis Investigative Site

Recruiting

Barcelona,Catalunya,08036,Spain

Novartis Investigative Site

Recruiting

Bern,3010,Switzerland

Novartis Investigative Site

Recruiting

Lausanne,1005,Switzerland

Novartis Investigative Site

Recruiting

Izmir,35575,Turkey

Novartis Investigative Site

Recruiting

Kocaeli,41380,Turkey

Novartis Investigative Site

Recruiting

Ankara,06500,Turkey

Novartis Investigative Site

Recruiting

Belfast,Bt9 7ab,United Kingdom

Novartis Investigative Site

Recruiting

Cardiff,Cf14 4xw,United Kingdom

Baylor Scott and White Research .

Recruiting

Temple,Texas,76502,United States

Childrens Hospital Colorado

Recruiting

Aurora,Colorado,80045,United States

Col Uni Med Center New York Presby

Recruiting

New York,New York,10032,United States

UCSF Main Centre

Recruiting

San Francisco,California,94115,United States

Massachusetts General Hospital Nephrology Department

Recruiting

Boston,Massachusetts,02114,United States

Univ Cali Irvine ALS Neuromuscular Tustin

Recruiting

Orange,California,92868,United States

Ronald Reagan UCLA Medical Center UCLA Connie Frank Clinic

Recruiting

Los Angeles,California,90095,United States

University of Minnesota Renal Disease and Hypertension

Recruiting

Minneapolis,Minnesota,55455,United States

Novartis Investigative Site

Recruiting

Ho Chi Minh,700000,Vietnam

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