Clinical trial NCT04817618: Study of Efficacy and Safety of Iptacopan in Patients With C3 Glomerulopathy.
Official title: A Multicenter, Randomized, Double-blind, Parallel Group, Placebo-controlled Study to Evaluate the Efficacy and Safety of Iptacopan (LNP023) in Complement 3 Glomerulopathy.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: C3G
Keywords: LNP023
iptacopan
C3G
UPCR
eGFR
proteinuria
Quality of life
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2021-03-26
Enrollment: 98
Sex: ALL
Minimum age (years): 12
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The Primary Completion Date and Study Completion Date have been updated to reflect completion of the adolescent cohort, which has been added to the protocol.

The study is designed as a multicenter, randomized, double-blind, parallel group, placebo-controlled study to evaluate the efficacy and safety of iptacopan (LNP023) in complement 3 glomerulopathy.

Detailed description: The purpose of this study is to evaluate the efficacy and safety of iptacopan compared to placebo and standard of care in patients with native C3G. CLNP023B12301 is a Phase 3 pivotal trial for registration of iptacopan in C3G. The study aims to determine the reduction in UPCR and improvement in eGFR in participants treated with iptacopan compared to placebo, as well as the proportion of participants who achieve a composite renal endpoint consisting of eGFR and UPCR elements. These effects of iptacopan in conjunction with increases in serum C3 levels will provide support for an iptacopan profile that includes stabilization of eGFR, clinically meaningful reductions in proteinuria and inhibition of the complement AP. Kidney biopsies will be performed in adult participants to evaluate histopathological improvements in immunofluorescence and light microscopy that support these functional benefits of iptacopan.

Eligibility criteria: Inclusion Criteria:

* Male and female participants age ≥ 12 and ≤ 60 years at screening.
* Diagnosis of C3G as confirmed by renal biopsy within 12 months prior to enrollment in adults and within 3 years in adolescents.
* Prior to randomization, all participants must have been on a maximally recommended or tolerated dose of an angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) for at least 90 days. The doses of other antiproteinuric medications including mycophenolic acid, corticosteroids and mineralocorticoid receptor antagonists should be stable for at least 90 days prior to randomization.
* Reduced serum C3 (defined as less than 0.85 x lower limit of the central laboratory normal range) at Screening.
* UPCR ≥ 1.0 g/g sampled from the first morning void urine sample at Day -75 and Day -15.
* Estimated GFR (using the CKD-EPI formula for ages ≥ 18 years and modified Schwartz formula for ages 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 prior to the start of study treatment.
* 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 study treatment has to start earlier than 2 weeks post vaccination, prophylactic antibiotic treatment should be initiated.

Exclusion Criteria:

* Participants who have received any cell or organ transplantation, including a kidney transplantation.
* Rapidly progressive crescentic glomerulonephritis defined as a 50% decline in the eGFR within 3 months with renal biopsy findings of glomerular crescent formation seen in at least 50% of glomeruli.
* Renal biopsy showing interstitial fibrosis/tubular atrophy (IF/TA) of more than 50%
* Monoclonal gammopathy of undetermined significance (MGUS) confirmed by the measurement of serum free light chains or other investigation as per local standard of care.
* Participants with an active systemic bacterial, viral or fungal infection within 14 days prior to study treatment administration
* 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., N. meningitidis and S. pneumoniae.
* The use of inhibitors of complement factors (e.g., Factor B, Factor D, C3 inhibitors, anti C5 antibodies, C5a receptor antagonists) within 6 months prior to the Screening visit.
* The use of immunosuppressants (except mycophenolic acids), cyclophosphamide or systemic corticosteroids at a dose \>7.5 mg/day (or equivalent for a similar medication) within 90 days of study drug administration.
* Acute post-infectious glomerulonephritis at screening based upon the opinion of the investigator.

Primary outcomes:
measure: Adult cohort: Log-transformed ratio to baseline in UPCR (sampled from a 24-hour urine collection)
timeFrame: 6 months (double-blind)
measure: Adolescent cohort: Log-transformed ratio to baseline in UPCR (sampled from a 24-hour urine collection)
timeFrame: 6 months (double-blind)
measure: Change from baseline in log-transformed UPCR at the 12-month visit (both study treatment arms).
timeFrame: 12 months (double-blind and open-label)
measure: Change in log-transformed UPCR from the 6-month visit to the 12-month visit in the placebo arm
timeFrame: From month 6 to month 12 (open-label)
Secondary outcomes:
measure: Change from baseline in eGFR.
timeFrame: 6 months (double-blind)
measure: Proportion of participants who meet the criteria for achieving a composite renal endpoint
timeFrame: 6 months (double-blind)
measure: Adult cohort: Change from baseline in disease total activity score in a renal biopsy.
timeFrame: 6 months (double-blind)
measure: Change from baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) score.
timeFrame: 6 months (double-blind)
measure: Number of participants with abnormal clinically significant vital signs, ECGs and safety laboratory measurements
timeFrame: 6 months (double-blind)
measure: Number of participants with study drug discontinuation due to an AE
timeFrame: 6 months (double-blind)
measure: Proportion of participants who meet the criteria for achieving a composite renal endpoint
timeFrame: 12 months (double-blind and open-label)
measure: Proportion of patients achieving a composite renal endpoint from the 6-month visit to the 12-month visit of the placebo arm
timeFrame: month 6, month 12 (open-label)
measure: Change from baseline in the total activity score in a renal biopsy at 12 months
timeFrame: Baseline, month 12 (double-blind and open-label)
measure: Change in the total activity score in a renal biopsy from the 6-month visit to the 12-month visit of the placebo arm.
timeFrame: month 6, month 12 (open-label)
measure: Change from baseline in the FACIT-Fatigue score at 12 months
timeFrame: Baseline, month 12 (double-blind and open-label)
measure: Change in the FACIT-Fatigue score from the 6-month visit to the 12-month visit of the placebo arm
timeFrame: month 6, month 12 (open-label)
measure: Number of participants with abnormal clinically significant vital signs, ECGs and safety laboratory measurements
timeFrame: 12 months (double-blind and open-label)
measure: Number of participants with study drug discontinuation due to an AE
timeFrame: 12 months (double-blind and open-label)
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Childrens Hospital Colorado
state: Colorado
city: Miami
country: United States
facility: Nicklaus Childrens Hospital
state: Florida
city: Lawrenceville
country: United States
facility: Georgia Nephrology Research Inst
state: Georgia
city: Iowa City
country: United States
facility: University of Iowa Health Care
state: Iowa
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Boston
country: United States
facility: Brigham and Womens Hosp Harvard Med School
state: Massachusetts
city: Albany
country: United States
facility: Albany Medical Center
state: New York
city: New York
country: United States
facility: Col Uni Med Center New York Presby
state: New York
city: Temple
country: United States
facility: Baylor Scott and White Research
state: Texas
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: Novartis Investigative Site
city: Cordoba
country: Argentina
facility: Novartis Investigative Site
city: Edegem
country: Belgium
facility: Novartis Investigative Site
city: Leuven
country: Belgium
facility: Novartis Investigative Site
city: Belo Horizonte
country: Brazil
facility: Novartis Investigative Site
state: MG
city: Pernambuco
country: Brazil
facility: Novartis Investigative Site
state: Recife
city: Passo Fundo
country: Brazil
facility: Novartis Investigative Site
state: RS
city: Joinville
country: Brazil
facility: Novartis Investigative Site
state: Santa Catarina
city: Santo Andre
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Sao Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Sao Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Salvador
country: Brazil
facility: Novartis Investigative Site
city: London
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Guangzhou
country: China
facility: Novartis Investigative Site
state: Guangdong
city: Beijing
country: China
facility: Novartis Investigative Site
city: Beijing
country: China
facility: Novartis Investigative Site
city: Shanghai
country: China
facility: Novartis Investigative Site
city: Wuhan
country: China
facility: Novartis Investigative Site
city: Praha
country: Czechia
facility: Novartis Investigative Site
city: Lille
country: France
facility: Novartis Investigative Site
city: Marseille
country: France
facility: Novartis Investigative Site
city: Montpellier 5
country: France
facility: Novartis Investigative Site
city: Paris 15
country: France
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Aachen
country: Germany
facility: Novartis Investigative Site
city: Erlangen
country: Germany
facility: Novartis Investigative Site
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Hannover
country: Germany
facility: Novartis Investigative Site
city: Heidelberg
country: Germany
facility: Novartis Investigative Site
city: Mainz
country: Germany
facility: Novartis Investigative Site
city: Athens
country: Greece
facility: Novartis Investigative Site
city: Heraklion Crete
country: Greece
facility: Novartis Investigative Site
city: Thessaloniki
country: Greece
facility: Novartis Investigative Site
city: Thessaloniki
country: Greece
facility: Novartis Investigative Site
city: New Delhi
country: India
facility: Novartis Investigative Site
state: Delhi
city: Hyderabad
country: India
facility: Novartis Investigative Site
state: Telangana
city: Lucknow
country: India
facility: Novartis Investigative Site
state: Uttar Pradesh
city: Dehradun
country: India
facility: Novartis Investigative Site
state: Uttarakhand
city: New Delhi
country: India
facility: Novartis Investigative Site
city: Petach Tikva
country: Israel
facility: Novartis Investigative Site
city: Petach Tikva
country: Israel
facility: Novartis Investigative Site
city: Ranica
country: Italy
facility: Novartis Investigative Site
state: BG
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Nagoya
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Asahikawa
country: Japan
facility: Novartis Investigative Site
state: Hokkaido
city: Sapporo
country: Japan
facility: Novartis Investigative Site
state: Hokkaido
city: Takatsuki
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Ohtsu
country: Japan
facility: Novartis Investigative Site
state: Shiga
city: Niigata
country: Japan
facility: Novartis Investigative Site
city: Leiden
country: Netherlands
facility: Novartis Investigative Site
state: Zuid Holland
city: Nijmegen
country: Netherlands
facility: Novartis Investigative Site
city: Malaga
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Sevilla
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Puerto De Sagunto
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Bern
country: Switzerland
facility: Novartis Investigative Site
city: Lausanne
country: Switzerland
facility: Novartis Investigative Site
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
state: TUR
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
city: Talas Kayseri
country: Turkey
facility: Novartis Investigative Site
city: Glasgow
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: Newcastle upon Tyne
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: