Clinical trial NCT06291376: Study of Ravulizumab in Immunoglobulin A Nephropathy (IgAN)
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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Immunoglobulin A Nephropathy
IgAN
Keywords: Immunoglobulin A nephropathy
IgAN
proteinuria
glomerulonephropathy
chronic kidney disease
CKD
Lead sponsor: Alexion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2024-03-04
Enrollment: 510
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of this study to evaluate efficacy of ravulizumab compared with placebo on proteinuria reduction and change in eGFR in adult participants with IgAN who are at risk of disease progression.

Detailed description: The I CAN study will enroll approximately 510 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. Approximately 450 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 60 participants with eGFR 20-29 mL/min/1.73m2 will be enrolled in an Advanced Kidney Disease (AdKD) Cohort After Week 106, all participants have the option to enter an Open-label Ravulizumab Access Period.

Eligibility criteria: Inclusion Criteria:

* Documentation of IgAN diagnosis established on kidney biopsy obtained any time prior to or during the Screening Period for participants with eGFR ≥ 30 mL/min/1.73 m\^2.
* For participants in the AdKD cohorts, eGFR 20 to 29 mL/min/1.73 m2 a kidney biopsy is required within 6 months prior to Screening or during the Screening Period.
* UPCR ≥ 0.75 g/g or UP ≥1 g/day calculated from the mean of two 24-hour urine during the Screening Period.
* Estimated GFR ≥ 30 mL/min/1.73 m2 at 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 receiving SGLT2I, DEARA, MRA or ERA must be on a stable and maximum allowed or tolerated dose for ≥ 3 months prior to Screening with no planned change in dose 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; IgAV-N may be eligible).
* Concomitant clinically significant renal disease other than IgAN.
* Prior use of immunosuppressive treatment within 3 months of screening.
* Uncontrolled diabetes mellitus with glycosylated hemoglobin (HbA1c) \> 8.5%.
* Henoch-Schonlein purpura (IgAV) requiring systemic immunosuppressive therapy within 12 months of 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.

Primary outcomes:
measure: Change from Baseline in Proteinuria Based on 24-hour Urine Protein Creatinine Ratio (UPCR) at Week 34
timeFrame: Baseline, Week 34
measure: Change from Baseline in Glomerular Filtration Rate (eGFR) at Week 106
timeFrame: Baseline, Week 106
Secondary outcomes:
measure: Change from Baseline in Proteinuria Based on 24-hour Urine Protein Creatinine Ratio (UPCR) at Weeks 10, 26, 34, 50, and 106
timeFrame: Baseline, Weeks 10, 26, 34, 50, and 106
measure: Change From Baseline in eGFR at Weeks 34 and 50
timeFrame: Baseline, Weeks 34 and 50
measure: Change From Baseline in Albuminuria at Each Scheduled Visit Up to Week 106
timeFrame: Baseline, at Each Scheduled Visit Up to Week 106
measure: Reduction in 24-hour UPCR ≥ 50% From Baseline at Each Scheduled Visit Up to Week 106
timeFrame: Baseline, at Each Scheduled Visit Up to Week 106
measure: Number of Participants With Partial Remission at Each Scheduled Visit Up to Week 106
timeFrame: Baseline, at Each Scheduled Visit Up to Week 106
measure: Change from Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue at Weeks 34, 50, and 106
timeFrame: Baseline, Weeks 34, 50, and 106
measure: Annualized eGFR Slope Over 50 Weeks
timeFrame: Baseline, Over 50 Weeks
measure: Time to First Composite Kidney Event Up to Week 106
timeFrame: Baseline Up to Week 106
measure: Time to Sustained ≥ 30% eGFR Decline Up to Week 106
timeFrame: Baseline Up to Week 106
measure: Time to Sustained eGFR Decline ≥ 40% Up to Week 106
timeFrame: Baseline Up to Week 106
measure: Use of Alternative IgAN Therapy Up to Week 106
timeFrame: Baseline, Up to Week 106
Other outcomes:
Locations:
city: Alabaster
country: United States
facility: Research Site
state: Alabama
city: Phoenix
country: United States
facility: Research Site
state: Arizona
city: Loma Linda
country: United States
facility: Research Site
state: California
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Northridge
country: United States
facility: Research Site
state: California
city: Orange
country: United States
facility: Research Site
state: California
city: San Diego
country: United States
facility: Research Site
state: California
city: San Francisco
country: United States
facility: Research Site
state: California
city: Stanford
country: United States
facility: Research Site
state: California
city: Torrance
country: United States
facility: Research Site
state: California
city: Aurora
country: United States
facility: Research Site
state: Colorado
city: Bay Pines
country: United States
facility: Research Site
state: Florida
city: Miami
country: United States
facility: Research Site
state: Florida
city: Orlando
country: United States
facility: Research Site
state: Florida
city: Acworth
country: United States
facility: Research Site
state: Georgia
city: Lawrenceville
country: United States
facility: Research Site
state: Georgia
city: Iowa City
country: United States
facility: Research Site
state: Iowa
city: New Orleans
country: United States
facility: Research Site
state: Louisiana
city: Shreveport
country: United States
facility: Research Site
state: Louisiana
city: Augusta
country: United States
facility: Research Site
state: Maine
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Pontiac
country: United States
facility: Research Site
state: Michigan
city: Minneapolis
country: United States
facility: Research Site
state: Minnesota
city: Minneapolis
country: United States
facility: Research Site
state: Minnesota
city: Kansas City
country: United States
facility: Research Site
state: Missouri
city: Saint Peters
country: United States
facility: Research Site
state: Missouri
city: North Las Vegas
country: United States
facility: Research Site
state: Nevada
city: Albany
country: United States
facility: Research Site
state: New York
city: Bronx
country: United States
facility: Research Site
state: New York
city: East Setauket
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: Columbus
country: United States
facility: Research Site
state: Ohio
city: Charleston
country: United States
facility: Research Site
state: South Carolina
city: Knoxville
country: United States
facility: Research Site
state: Tennessee
city: Arlington
country: United States
facility: Research Site
state: Texas
city: Houston
country: United States
facility: Research Site
state: Texas
city: Houston
country: United States
facility: Research Site
state: Texas
city: San Antonio
country: United States
facility: Research Site
state: Texas
city: Shenandoah
country: United States
facility: Research Site
state: Texas
city: Charlottesville
country: United States
facility: Research Site
state: Virginia
city: Milwaukee
country: United States
facility: Research Site
state: Wisconsin
city: Buenos Aires
country: Argentina
facility: Research Site
city: Ciudad Autonoma Bs As
country: Argentina
facility: Research Site
city: Cordoba
country: Argentina
facility: Research Site
city: Florencio Varela
country: Argentina
facility: Research Site
city: La Plata
country: Argentina
facility: Research Site
city: Rosario
country: Argentina
facility: Research Site
city: San Luis
country: Argentina
facility: Research Site
city: Camperdown
country: Australia
facility: Research Site
city: Canberra
country: Australia
facility: Research Site
city: Clayton
country: Australia
facility: Research Site
city: Concord
country: Australia
facility: Research Site
city: Herston
country: Australia
facility: Research Site
city: Liverpool
country: Australia
facility: Research Site
city: Parkville
country: Australia
facility: Research Site
city: Perth
country: Australia
facility: Research Site
city: Southport
country: Australia
facility: Research Site
city: St Albans
country: Australia
facility: Research Site
city: Graz
country: Austria
facility: Research Site
city: Innsbruck
country: Austria
facility: Research Site
city: Linz
country: Austria
facility: Research Site
city: Brussels
country: Belgium
facility: Research Site
city: Edegem
country: Belgium
facility: Research Site
city: Leuven
country: Belgium
facility: Research Site
city: Liège
country: Belgium
facility: Research Site
city: Roeselare
country: Belgium
facility: Research Site
city: Belo Horizonte
country: Brazil
facility: Research Site
city: Belo Horizonte
country: Brazil
facility: Research Site
city: Belo Horizonte
country: Brazil
facility: Research Site
city: Botucatu
country: Brazil
facility: Research Site
city: Curitiba
country: Brazil
facility: Research Site
city: Fortaleza
country: Brazil
facility: Research Site
city: Recife
country: Brazil
facility: Research Site
city: Ribeirão Preto
country: Brazil
facility: Research Site
city: S.J. Do Rio Preto
country: Brazil
facility: Research Site
city: Salvador
country: Brazil
facility: Research Site
city: São Paulo
country: Brazil
facility: Research Site
city: São Paulo
country: Brazil
facility: Research Site
city: Winnipeg
country: Canada
facility: Research Site
state: Manitoba
city: London
country: Canada
facility: Research Site
state: Ontario
city: Ottawa
country: Canada
facility: Research Site
state: Ontario
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Araucania
country: Chile
facility: Research Site
city: Providencia
country: Chile
facility: Research Site
city: Santiago
country: Chile
facility: Research Site
city: Santiago
country: Chile
facility: Research Site
city: Valdivia
country: Chile
facility: Research Site
city: Baotou
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Changsha
country: China
facility: Research Site
city: Changzhou
country: China
facility: Research Site
city: Chengdu
country: China
facility: Research Site
city: Chengdu
country: China
facility: Research Site
city: Chongqing
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Hangzhou
country: China
facility: Research Site
city: Hangzhou
country: China
facility: Research Site
city: Jinan
country: China
facility: Research Site
city: Jinan
country: China
facility: Research Site
city: Jinhua
country: China
facility: Research Site
city: Lanzhou
country: China
facility: Research Site
city: Luoyang
country: China
facility: Research Site
city: Nanchang
country: China
facility: Research Site
city: Nanchang
country: China
facility: Research Site
city: Nanjing
country: China
facility: Research Site
city: Nanjing
country: China
facility: Research Site
city: Nanjing
country: China
facility: Research Site
city: Ningbo
country: China
facility: Research Site
city: Qingdao
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shenyang
country: China
facility: Research Site
city: Shenzhen
country: China
facility: Research Site
city: Shenzhen
country: China
facility: Research Site
city: Urumqi
country: China
facility: Research Site
city: Wuhan
country: China
facility: Research Site
city: Wuxi
country: China
facility: Research Site
city: Xian
country: China
facility: Research Site
city: Yantai
country: China
facility: Research Site
city: Yibin
country: China
facility: Research Site
city: Yinchuan
country: China
facility: Research Site
city: Zhanjiang
country: China
facility: Research Site
city: Zhengzhou
country: China
facility: Research Site
city: Zhongshan
country: China
facility: Research Site
city: Barranquilla
country: Colombia
facility: Research Site
city: Bogota
country: Colombia
facility: Research Site
city: Cali
country: Colombia
facility: Research Site
city: Manizales
country: Colombia
facility: Research Site
city: Medellín
country: Colombia
facility: Research Site
city: Rionegro
country: Colombia
facility: Research Site
city: Nový Jičín
country: Czechia
facility: Research Site
city: Praha 2
country: Czechia
facility: Research Site
city: Praha 4
country: Czechia
facility: Research Site
city: Amiens
country: France
facility: Research Site
city: Bayonne
country: France
facility: Research Site
city: Brest Cedex
country: France
facility: Research Site
city: Chambéry
country: France
facility: Research Site
city: Clermont Ferrand
country: France
facility: Research Site
city: Le Kremlin-Bicêtre
country: France
facility: Research Site
city: Marseille
country: France
facility: Research Site
city: Nantes
country: France
facility: Research Site
city: Nice
country: France
facility: Research Site
city: Paris
country: France
facility: Research Site
city: Paris
country: France
facility: Research Site
city: Paris
country: France
facility: Research Site
city: Saint-Priest-en-Jarez
country: France
facility: Research Site
city: Strasbourg
country: France
facility: Research Site
city: Toulouse
country: France
facility: Research Site
city: Aachen
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Erlangen
country: Germany
facility: Research Site
city: Essen
country: Germany
facility: Research Site
city: Greifswald
country: Germany
facility: Research Site
city: Hannover
country: Germany
facility: Research Site
city: Konstanz
country: Germany
facility: Research Site
city: Köln
country: Germany
facility: Research Site
city: Mainz
country: Germany
facility: Research Site
city: München
country: Germany
facility: Research Site
city: München
country: Germany
facility: Research Site
city: Villingen-Schwenningen
country: Germany
facility: Research Site
city: Athens
country: Greece
facility: Research Site
city: Athens
country: Greece
facility: Research Site
city: Heraclion
country: Greece
facility: Research Site
city: Patras
country: Greece
facility: Research Site
city: Thessaloniki
country: Greece
facility: Research Site
city: Hong Kong
country: Hong Kong
facility: Research Site
city: Hong Kong
country: Hong Kong
facility: Research Site
city: Lai Chi Kok
country: Hong Kong
facility: Research Site
city: Shatin
country: Hong Kong
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Miskolc
country: Hungary
facility: Research Site
city: Haifa
country: Israel
facility: Research Site
city: Jerusalem
country: Israel
facility: Research Site
city: Nazareth
country: Israel
facility: Research Site
city: Petah Tikva
country: Israel
facility: Research Site
city: Tel Aviv
country: Israel
facility: Research Site
city: Agrigento
country: Italy
facility: Research Site
city: Bari
country: Italy
facility: Research Site
city: Bologna
country: Italy
facility: Research Site
city: Brescia
country: Italy
facility: Research Site
city: Cagliari
country: Italy
facility: Research Site
city: Firenze
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Padova
country: Italy
facility: Research Site
city: Parma
country: Italy
facility: Research Site
city: Piacenza
country: Italy
facility: Research Site
city: Torino
country: Italy
facility: Research Site
city: Torrette
country: Italy
facility: Research Site
city: Verona
country: Italy
facility: Research Site
city: Ashikaga
country: Japan
facility: Research Site
city: Bunkyo-ku
country: Japan
facility: Research Site
city: Chiba-shi
country: Japan
facility: Research Site
city: Chiba-shi
country: Japan
facility: Research Site
city: Fukuoka-shi
country: Japan
facility: Research Site
city: Kamakura
country: Japan
facility: Research Site
city: Kasugai-shi
country: Japan
facility: Research Site
city: Kitakyushu-shi
country: Japan
facility: Research Site
city: Kobe-shi
country: Japan
facility: Research Site
city: Matsumoto-shi
country: Japan
facility: Research Site
city: Matsuyama-shi
country: Japan
facility: Research Site
city: Nagoya
country: Japan
facility: Research Site
city: Osaka-shi
country: Japan
facility: Research Site
city: Osaka-shi
country: Japan
facility: Research Site
city: Sapporo-shi
country: Japan
facility: Research Site
city: Toyota-Shi
country: Japan
facility: Research Site
city: Urayasu-shi
country: Japan
facility: Research Site
city: Anyang-si
country: Korea, Republic of
facility: Research Site
city: Busan
country: Korea, Republic of
facility: Research Site
city: Deagu
country: Korea, Republic of
facility: Research Site
city: Gwangju
country: Korea, Republic of
facility: Research Site
city: Gyeonggi-do
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Suwon-si
country: Korea, Republic of
facility: Research Site
city: Ipoh
country: Malaysia
facility: Research Site
city: Johor Bahru
country: Malaysia
facility: Research Site
city: Kuala Lumpur
country: Malaysia
facility: Research Site
city: Seremban
country: Malaysia
facility: Research Site
city: Taiping
country: Malaysia
facility: Research Site
city: Chihuahua
country: Mexico
facility: Research Site
city: Culiacan
country: Mexico
facility: Research Site
city: Guadalajara
country: Mexico
facility: Research Site
city: Juriquilla
country: Mexico
facility: Research Site
city: Mexico
country: Mexico
facility: Research Site
city: Zapopan
country: Mexico
facility: Research Site
city: Amsterdam
country: Netherlands
facility: Research Site
city: Groningen
country: Netherlands
facility: Research Site
city: Nijmegen
country: Netherlands
facility: Research Site
city: Rotterdam
country: Netherlands
facility: Research Site
city: Białystok
country: Poland
facility: Research Site
city: Białystok
country: Poland
facility: Research Site
city: Kraków
country: Poland
facility: Research Site
city: Lublin
country: Poland
facility: Research Site
city: Olsztyn
country: Poland
facility: Research Site
city: Poznań
country: Poland
facility: Research Site
city: Szczecin
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Łódź
country: Poland
facility: Research Site
city: Braga
country: Portugal
facility: Research Site
city: Funchal
country: Portugal
facility: Research Site
city: Lisbon
country: Portugal
facility: Research Site
city: Porto
country: Portugal
facility: Research Site
city: Torres Novas
country: Portugal
facility: Research Site
city: Bucuresti
country: Romania
facility: Research Site
city: Cluj Napoca
country: Romania
facility: Research Site
city: Timisoara
country: Romania
facility: Research Site
city: Dammam
country: Saudi Arabia
facility: Research Site
city: Jeddah
country: Saudi Arabia
facility: Research Site
city: Riyadh
country: Saudi Arabia
facility: Research Site
city: Riyadh
country: Saudi Arabia
facility: Research Site
city: Riyadh
country: Saudi Arabia
facility: Research Site
city: Riyadh
country: Saudi Arabia
facility: Research Site
city: Banská Bystrica
country: Slovakia
facility: Research Site
city: Bratislava
country: Slovakia
facility: Research Site
city: Košice
country: Slovakia
facility: Research Site
city: Martin
country: Slovakia
facility: Research Site
city: Alcalá de Henares
country: Spain
facility: Research Site
city: La Coruña
country: Spain
facility: Research Site
city: Lérida
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Murcia
country: Spain
facility: Research Site
city: Málaga
country: Spain
facility: Research Site
city: Oviedo
country: Spain
facility: Research Site
city: Sant Joan Despí
country: Spain
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
city: Tarragona
country: Spain
facility: Research Site
city: Valencia
country: Spain
facility: Research Site
city: Zaragoza
country: Spain
facility: Research Site
city: Kaohsiung City
country: Taiwan
facility: Research Site
city: Kaohsiung
country: Taiwan
facility: Research Site
city: Kaohsiung
country: Taiwan
facility: Research Site
city: New Taipei City
country: Taiwan
facility: Research Site
city: New Taipei City
country: Taiwan
facility: Research Site
city: Taichung City
country: Taiwan
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Tainan City
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taoyuan City
country: Taiwan
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Chaingmai
country: Thailand
facility: Research Site
city: Khlong Luang
country: Thailand
facility: Research Site
city: Khon Kaen
country: Thailand
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Bursa
country: Turkey
facility: Research Site
city: Istanbul
country: Turkey
facility: Research Site
city: Istanbul
country: Turkey
facility: Research Site
city: Kahramanmaras
country: Turkey
facility: Research Site
city: Kayseri
country: Turkey
facility: Research Site
city: Kocaeli
country: Turkey
facility: Research Site
city: Konya
country: Turkey
facility: Research Site
city: Pamukkale
country: Turkey
facility: Research Site
city: Cambridge
country: United Kingdom
facility: Research Site
city: Doncaster
country: United Kingdom
facility: Research Site
city: Dundee
country: United Kingdom
facility: Research Site
city: Leicester
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Reading
country: United Kingdom
facility: Research Site
city: Salford
country: United Kingdom
facility: Research Site
city: Stevenage
country: United Kingdom
facility: Research Site
Study officials:
References: