Study of Ravulizumab in Immunoglobulin A Nephropathy (IgAN)

Immunoglobulin A Nephropathy Clinical Trial

— ICAN  

Official title:

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Ravulizumab in Adult Participants With Immunoglobulin A Nephropathy (IgAN)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06291376
• Other study ID #: D928FC00001
• Status: Recruiting
• Phase: Phase 3
• Start date: March 29, 2024
• Est. completion date: October 25, 2029

Study information

• Verified date: May 2024
• Source: Alexion Pharmaceuticals, Inc.
• Contact: Alexion Pharmaceuticals, Inc. (Sponsor)
• Phone: 1-855-752-2356
• Email: clinicaltrials[@]alexion.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study to evaluate the efficacy of ravulizumab compared with placebo to reduce proteinuria and slow the rate of eGFR decline in adult participants with IgAN who are at risk of disease progression.

Description:

The I CAN study will enroll approximately 450 eligible participants with IgAN who are high risk of disease progression. Participants will be on stable concomitant IgAN treatment(s) consistent with standard of care for patients with IgAN for at least 3 months prior to Screening, Participants will be randomized in a 1:1 allocation ratio to receive a weight-based IV infusion of either ravulizumab or placebo. An interim analysis may be conducted at Week 34 to evaluate change in proteinuria and the final analysis will be conducted at Week 106 to evaluate eGFR. In addition, approximately 20 participants with eGFR 20-29 mL/min/1.73m2 will be enrolled in an Exploratory Cohort and will receive open label weight-based IV infusion of ravulizumab. After Week 106, all participants have the option to enter a post-study access period and receive open-label ravulizumab.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 470
• Est. completion date: October 25, 2029
• Est. primary completion date: February 23, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Documentation of IgAN diagnosis established on kidney biopsy obtained any time prior to or during the Screening Period.
• UPCR = 0.75 g/g or UP =1 g/day from the mean of two 24-hour urine collections during Screening.
• Estimated GFR = 30 mL/min/1.73 m2 at Screening.
• Exploratory Cohort: eGFR 20-29 mL/min/1.73 m2 at Screening. A kidney biopsy is required within 6 months prior to Screening or during the Screening Period.
• Presence of hematuria as defined by a positive result on urine dipstick for blood or = 5 red blood cells (RBCs)/high power field microscopy on urine sediment during or within 3 months of Screening.
• Stable and maximum allowed or tolerated RASI (ACEI and/or ARB) dose for = 3 months prior to Screening with no planned change during Screening through Week 106.
• Participants who are on an SGLT2I, ERA, or MRA must be on a stable and maximum allowed or tolerated dose for = 3 months prior to Screening with no planned change through Week 106.

Exclusion Criteria:

• Diagnosis of rapid progressive glomerulonephritis as measured by eGFR loss = 50% over a period of 3 months prior to Screening.
• Secondary IgAN (eg, due to systemic lupus erythematosus (SLE), cirrhosis, or celiac disease).
• Concomitant clinically significant renal disease other than IgAN.
• Prior use of immunosuppressive treatment for IgAN within 6 months of screening.
• Uncontrolled diabetes mellitus with glycosylated hemoglobin (HbA1c) > 8.5%.
• Clinically active Henoch-Schonlein purpura (IgA vasculitis) requiring ongoing systemic immunosuppressive therapy at Screening.
• History of kidney transplant or planned kidney transplant during the Treatment Period.
• Splenectomy or functional asplenia.
• History of Neisseria meningitidis infection.
• Active systemic bacterial, viral, or fungal infection within 14 days prior to randomization.

Related Conditions & MeSH terms

• Glomerulonephritis, IGA
• IgAN
• Immunoglobulin A Nephropathy
• Kidney Diseases

Intervention

Drug:
• Ravulizumab
Participants will receive ravulizumab via weight-based intravenous (IV) infusion.
• Placebo
Participants will receive placebo via weight-based IV infusion.

Locations

Country	Name	City	State
Argentina	Research Site	Ciudad Autonoma Bs As
Argentina	Research Site	Córdoba
Argentina	Research Site	La Plata
Argentina	Research Site	Rosario
Argentina	Research Site	San Luis
Australia	Research Site	Canberra
Australia	Research Site	Clayton
Australia	Research Site	Concord
Australia	Research Site	Herston
Australia	Research Site	Liverpool
Australia	Research Site	Southport
Australia	Research Site	St Albans
Austria	Research Site	Graz
Austria	Research Site	Innsbruck
Austria	Research Site	Linz
Belgium	Research Site	Brussels
Belgium	Research Site	Edegem
Belgium	Research Site	Leuven
Belgium	Research Site	Liège
Belgium	Research Site	Roeselare
Brazil	Research Site	Belo Horizonte
Brazil	Research Site	Belo Horizonte
Brazil	Research Site	Botucatu
Brazil	Research Site	Curitiba
Brazil	Research Site	Fortaleza
Brazil	Research Site	Recife
Brazil	Research Site	Ribeirão Preto
Brazil	Research Site	S.J. Do Rio Preto
Brazil	Research Site	Salvador
Brazil	Research Site	São Paulo
Brazil	Research Site	São Paulo
Canada	Research Site	London	Ontario
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Winnipeg	Manitoba
Chile	Research Site	Araucania
Chile	Research Site	Providencia
Chile	Research Site	Santiago
Chile	Research Site	Santiago
Chile	Research Site	Valdivia
China	Research Site	Baotou
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Changsha
China	Research Site	Chengdu
China	Research Site	Chengdu
China	Research Site	Chongqing
China	Research Site	Guangzhou
China	Research Site	Guangzhou
China	Research Site	Guangzhou
China	Research Site	Hangzhou
China	Research Site	Hangzhou
China	Research Site	Jinan
China	Research Site	Jinan
China	Research Site	Jinhua
China	Research Site	Lanzhou
China	Research Site	Luoyang
China	Research Site	Nanchang
China	Research Site	Nanchang
China	Research Site	Nanjing
China	Research Site	Nanjing
China	Research Site	Nanjing
China	Research Site	Ningbo
China	Research Site	Qingdao
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Shenyang
China	Research Site	Shenzhen
China	Research Site	Shenzhen
China	Research Site	Urumqi
China	Research Site	Wuhan
China	Research Site	Wuxi
China	Research Site	Xian
China	Research Site	Yantai
China	Research Site	Yibin
China	Research Site	Yinchuan
China	Research Site	Zhanjiang
China	Research Site	Zhengzhou
Colombia	Research Site	Barranquilla
Colombia	Research Site	Bogota
Colombia	Research Site	Cali
Colombia	Research Site	Rionegro
Czechia	Research Site	Nový Jicín
Czechia	Research Site	Praha 2
Czechia	Research Site	Praha 4
France	Research Site	Amiens Cedex 1
France	Research Site	Bayonne
France	Research Site	Brest Cedex
France	Research Site	Chambéry Cedex
France	Research Site	Clermont Ferrand
France	Research Site	Le Kremlin-Bicêtre
France	Research Site	Marseille
France	Research Site	Nantes
France	Research Site	Nice cedex 1
France	Research Site	Paris
France	Research Site	Paris
France	Research Site	Sr Priest En Jarez
France	Research Site	Strasbourg
France	Research Site	Toulouse
Germany	Research Site	Aachen
Germany	Research Site	Berlin
Germany	Research Site	Erlangen
Germany	Research Site	Essen
Germany	Research Site	Greifswald
Germany	Research Site	Hannover
Germany	Research Site	Köln
Germany	Research Site	Mainz
Germany	Research Site	München
Germany	Research Site	München
Germany	Research Site	Villingen-Schwenningen
Greece	Research Site	Athens
Greece	Research Site	Athens
Greece	Research Site	Heraclion
Greece	Research Site	Patras
Greece	Research Site	Thessaloniki
Hungary	Research Site	Budapest
Hungary	Research Site	Miskolc
Israel	Research Site	Haifa
Israel	Research Site	Jerusalem
Israel	Research Site	Nazareth
Israel	Research Site	Petah Tikva
Israel	Research Site	Tel Aviv
Italy	Research Site	Agrigento
Italy	Research Site	Bari
Italy	Research Site	Bologna
Italy	Research Site	Brescia
Italy	Research Site	Cagliari
Italy	Research Site	Firenze
Italy	Research Site	Milano
Italy	Research Site	Milano
Italy	Research Site	Padova
Italy	Research Site	Parma
Italy	Research Site	Piacenza
Italy	Research Site	Torino
Italy	Research Site	Torrette
Italy	Research Site	Verona
Japan	Research Site	Ashikaga
Japan	Research Site	Bunkyo-ku
Japan	Research Site	Chiba-Shi
Japan	Research Site	Chiba-shi
Japan	Research Site	Fukuoka-shi
Japan	Research Site	Kamakura
Japan	Research Site	Kasugai-shi
Japan	Research Site	Kitakyushu-shi
Japan	Research Site	Matsumoto-shi
Japan	Research Site	Matsuyama-shi
Japan	Research Site	Nagoya
Japan	Research Site	Osaka-shi
Japan	Research Site	Osaka-shi
Japan	Research Site	Sapporo-shi
Japan	Research Site	Toyota-Shi
Japan	Research Site	Urayasu-shi
Korea, Republic of	Research Site	Anyang-si
Korea, Republic of	Research Site	Busan
Korea, Republic of	Research Site	Deagu
Korea, Republic of	Research Site	Gwangju
Korea, Republic of	Research Site	Gyeonggi-do
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Suwon-si
Malaysia	Research Site	Ipoh
Malaysia	Research Site	Johor Bahru
Malaysia	Research Site	Kuala Lumpur
Malaysia	Research Site	Seremban
Malaysia	Research Site	Taiping
Mexico	Research Site	Chihuahua
Mexico	Research Site	Culiacan
Mexico	Research Site	Guadalajara
Mexico	Research Site	Juriquilla
Mexico	Research Site	Mexico
Mexico	Research Site	Zapopan
Netherlands	Research Site	Amsterdam
Netherlands	Research Site	Groningen
Netherlands	Research Site	Nijmegen
Poland	Research Site	Bialystok
Poland	Research Site	Bialystok
Poland	Research Site	Kraków
Poland	Research Site	Lódz
Poland	Research Site	Lublin
Poland	Research Site	Olsztyn
Poland	Research Site	Poznan
Poland	Research Site	Szczecin
Poland	Research Site	Warszawa
Poland	Research Site	Warszawa
Saudi Arabia	Research Site	Dammam
Saudi Arabia	Research Site	Riyadh
Saudi Arabia	Research Site	Riyadh
Slovakia	Research Site	Banská Bystrica
Slovakia	Research Site	Bratislava
Slovakia	Research Site	Martin
Spain	Research Site	Alcalá de Henares
Spain	Research Site	La Coruña
Spain	Research Site	Lérida
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Málaga
Spain	Research Site	Oviedo
Spain	Research Site	Sant Joan Despí
Spain	Research Site	Sevilla
Spain	Research Site	Tarragona
Spain	Research Site	Valencia
Spain	Research Site	Zaragoza
Taiwan	Research Site	Kaohsiung
Taiwan	Research Site	Kaohsiung City
Taiwan	Research Site	New Taipei City
Taiwan	Research Site	Taichung
Taiwan	Research Site	Taichung City
Taiwan	Research Site	Tainan City
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taoyuan City
Thailand	Research Site	Bangkok
Thailand	Research Site	Bangkok
Thailand	Research Site	Bangkok
Thailand	Research Site	Chaingmai
Thailand	Research Site	Khlong Luang
Thailand	Research Site	Khon Kaen
Turkey	Research Site	Ankara
Turkey	Research Site	Ankara
Turkey	Research Site	Bursa
Turkey	Research Site	Istanbul
Turkey	Research Site	Istanbul
Turkey	Research Site	Kayseri
Turkey	Research Site	Kocaeli
Turkey	Research Site	Konya
United Kingdom	Research Site	Cambridge
United Kingdom	Research Site	Doncaster
United Kingdom	Research Site	Leicester
United Kingdom	Research Site	London
United Kingdom	Research Site	London
United Kingdom	Research Site	London
United Kingdom	Research Site	Salford
United States	Research Site	Acworth	Georgia
United States	Research Site	Alabaster	Alabama
United States	Research Site	Albany	New York
United States	Research Site	Arlington	Texas
United States	Research Site	Augusta	Maine
United States	Research Site	Aurora	Colorado
United States	Research Site	Bay Pines	Florida
United States	Research Site	Boston	Massachusetts
United States	Research Site	Boston	Massachusetts
United States	Research Site	Bronx	New York
United States	Research Site	Charleston	South Carolina
United States	Research Site	Charlottesville	Virginia
United States	Research Site	East Setauket	New York
United States	Research Site	Houston	Texas
United States	Research Site	Lawrenceville	Georgia
United States	Research Site	Loma Linda	California
United States	Research Site	Los Angeles	California
United States	Research Site	Los Angeles	California
United States	Research Site	Los Angeles	California
United States	Research Site	Miami	Florida
United States	Research Site	Milwaukee	Wisconsin
United States	Research Site	Minneapolis	Minnesota
United States	Research Site	Minneapolis	Minnesota
United States	Research Site	North Las Vegas	Nevada
United States	Research Site	Orlando	Florida
United States	Research Site	Phoenix	Arizona
United States	Research Site	Pontiac	Michigan
United States	Research Site	Saint Peters	Missouri
United States	Research Site	San Francisco	California
United States	Research Site	Shenandoah	Texas
United States	Research Site	Stanford	California
United States	Research Site	Torrance	California

Sponsors (1)

Lead Sponsor	Collaborator
Alexion Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Canada,  Chile,  China,  Colombia,  Czechia,  France,  Germany,  Greece,  Hungary,  Israel,  Italy,  Japan,  Korea, Republic of,  Malaysia,  Mexico,  Netherlands,  Poland,  Saudi Arabia,  Slovakia,  Spain,  Taiwan,  Thailand,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from Baseline in Proteinuria Based on 24-hour Urine Protein Creatinine Ratio (UPCR) at Week 34	Evaluated at interim analysis only	Baseline, Week 34
Primary	Glomerular Filtration Rate (eGFR) Over 106 Weeks	Evaluated at final analysis only	Up to Week 106
Secondary	Change from Baseline in Proteinuria Based on 24-hour Urine Protein Creatinine Ratio (UPCR) at Weeks 10, 26, 34, 50, and 106	Evaluated at interim and final analysis	Baseline, Weeks 10, 26, 34, 50, and 106
Secondary	Change From Baseline in eGFR at Weeks 34, 50, and 106	Evaluated at interim and final analysis	Baseline, Weeks 34, 50, and 106
Secondary	Change From Baseline in Albuminuria Based on Urine Albumin to Creatinine Ratio (UACR) at Weeks 10, 26, 34, 50, and 106	Evaluated at interim and final analysis	Baseline, Weeks 10, 26, 34,50, and 106
Secondary	Reduction in 24-hour UPCR = 50% From Baseline to Weeks 10, 26, 34, 50, and 106	Evaluated at interim and final analysis	Baseline, Weeks 10, 26, 34, 50, and 106
Secondary	Number of Participants With Partial Remission at Weeks 34, 50, and 106	Evaluated at interim and final analysis	Weeks 34, 50, and 106
Secondary	Change from Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue at Weeks 34, 50, and 106	Evaluated at interim and final analysis	Baseline, Weeks 34, 50, and 106
Secondary	Number of Participants With Composite Kidney Failure Endpoint	Composite kidney failure endpoint is defined as reaching at least 1 of the following: Sustained = 30% decline in eGFR relative to baseline; or Sustained eGFR < 15 milliliter (mL)/minute (min)/1.73 square meter (m^2); or Maintenance dialysis; or Receipt of kidney transplant; or Death from kidney failure.; Evaluated at the final analysis only	Baseline up to Week 106
Secondary	Reduction in 24-hour UPCR = 50% From Baseline at both Weeks 34 and 106	Evaluated at the final analysis only	Baseline, Weeks 34 and 106
Secondary	Number of Participants With Kidney Hierarchical Composite Endpoint	The kidney hierarchical composite endpoint is defined as the most severe outcome of a participant according to the following severity of outcomes: death from kidney failure, kidney transplant, maintenance dialysis, sustained eGFR < 15 mL/min/1.73 m^2, sustained eGFR decline from baseline = 30%, or eGFR slope.; Evaluated at the final analysis only	Baseline up to Week 106