Clinical trial NCT05648968: A Study of Efficacy and Safety of Ianalumab in Previously Treated Patients With Warm Autoimmune Hemolytic Anemia
Official title: A Phase 3, Randomized, Double-blind, Study to Assess Efficacy and Safety of Ianalumab (VAY736) Versus Placebo in Warm Autoimmune Hemolytic Anemia (wAIHA) Patients Who Failed at Least One Line of Treatment
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Warm Autoimmune Hemolytic Anemia (wAIHA)
Keywords: warm autoimmune hemolytic anemia
wAIHA
ianalumab
VAY736
B-cell depletion
B-cell Activating Factor Receptor (BAFF-R) blockade
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2022-12-13
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate efficacy and safety of ianalumab compared to placebo in patients with warm autoimmune hemolytic anemia, who failed at least one line of treatment.

Detailed description: The primary objective is to demonstrate that either dose of ianalumab induces a durable hemoglobin response compared to placebo in patients with wAIHA.

The key secondary objective is to demonstrate that either dose of ianalumab maintains a durable hemoglobin response that is sustained beyond end of the treatment period, compared to placebo.

Participants are randomized to two different doses of ianalumab or placebo. Participants who were assigned to placebo arm and not responding to treatment may be treated with open label ianalumab using the higher dose.

The investigational treatment will be supplied in a double-blinded manner. For the open label period, ianalumab will be provided in an open label manner.

In addition to the randomized treatment (ianalumab or placebo), specific supportive care medication as defined in the protocol is allowed. If clinically indicated (e.g., to ensure patient safety), the treating physician may also administer rescue medication.

The study consists of the treatment period, efficacy and safety follow-up periods. The visit frequency will be every other week during the treatment and primary endpoint follow up period; for safety monitoring monthly during the first 20 weeks after last dose and afterwards quarterly up to 2 years from the last dose. For participants in durable response, additional visits for efficacy will occur monthly during the first 2 years after the last dose, and afterwards quarterly until loss of response or end of study, latest until up to 39 months post randomization of the last participant.

Eligibility criteria: Key Inclusion Criteria:

* 18 years and older at time of signing consent
* Patients with primary or secondary wAIHA documented by positive direct antiglobulin test specific for anti-IgG or anti-IgA, who had an insufficient response to, or relapsed after at least one line of treatment, including patients with steroid resistance, dependence or intolerance
* Hemoglobin concentration at screening and at Week 1 \>=5 g/dL and \<10 g/dL, associated with presence of symptoms related to anemia
* The dose of supportive care must be stable for at least 4 weeks prior to randomization into the study

Key Exclusion Criteria:

* wAIHA secondary to hematologic disease involving bone marrow (e.g., CLL) or another immunologic disease requiring prohibited medication as per protocol. Patients with autoimmune diseases after wash-out from the treatments are allowed.
* Presence of other forms of AIHA (cold or intermediate forms), Evans Syndrome or other cytopenias
* Prior use of B-cell depleting therapy (e.g., rituximab) within 12 weeks prior to randomization, or without hematological response to the last course of B-cell depleting therapy
* Neutrophils: \<1000/mm3
* Serum creatinine \>1.5 × upper limit of normal (ULN)
* Immunoglobulin G (IgG) \<5g/L
* Active viral, bacterial or other infections (including tuberculosis and SARS-CoV-2) requiring systemic treatment at time of screening, or history of recurrent clinically significant infection
* Positivity for hepatitis C virus, hepatitis B surface antigen (HBsAg), or hepatitis B core antibody (HBcAb). HBcAb positive patients can be enrolled if HBsAg negative, HBV DNA negative, no pre-existing liver fibrosis is present and antiviral prophylaxis is given.
* Known history of primary or secondary immunodeficiency, or a positive human immune deficiency virus (HIV) test result
* Live or live-attenuated vaccination within 4 weeks before randomization
* History of splenectomy

Other protocol-defined Inclusion/Exclusion may apply.

Primary outcomes:
measure: Binary variable indicating whether a patient achieves a durable response
timeFrame: Randomization to Week 25
Secondary outcomes:
measure: Duration of response (Key Secondary)
timeFrame: Randomization to end of study (up to 39 months after randomization of last patient)
measure: Time from randomization to start of durable response in each treatment group
timeFrame: Randomization to end of study (up to 39 months after randomization of last patient)
measure: Time from randomization to start of first response in each treatment group
timeFrame: Randomization to end of study (up to 39 months after randomization of last patient)
measure: Time from randomization to start of complete response in each treatment group
timeFrame: Randomization to end of study (up to 39 months after randomization of last patient)
measure: Response rate
timeFrame: Randomization to end of study (up to 39 months after randomization of last patient)
measure: Complete response rate
timeFrame: Randomization to end of study (up to 39 months after randomization of last patient)
measure: Hemoglobine Levels
timeFrame: Randomization to end of study (up to 39 months after randomization of last patient)
measure: Number of participants who received rescue treatment (overall & by type of rescue treatment)
timeFrame: Randomization to end of study (up to 39 months after randomization of last patient)
measure: Percentage of participants who received rescue treatment (overall & by type of rescue treatment)
timeFrame: Randomization to end of study (up to 39 months after randomization of last patient)
measure: Change from baseline in the the frequency and absolute number of CD19+ B cell counts
timeFrame: Randomization to end of study (up to 39 months after randomization of last patient)
measure: Time to first occurrence of B cell recovery, defined as ≥80% of baseline or ≥50 cells/μL
timeFrame: Randomization to end of study (up to 39 months after randomization of last patient)
measure: Change from baseline in immunoglobulin levels
timeFrame: Randomization until month 30
measure: Change from baseline in the 8 domain scores and in the summary scores (PCS, MCS) of SF-36 questionnaire
timeFrame: Randomization to end of study (up to 39 months after randomization of last patient)
measure: Change from baseline in the T-score of PROMIS Fatigue-13a questionnaire
timeFrame: Randomization to end of study (up to 39 months after randomization of last patient)
measure: Ianalumab PK parameter - AUClast
timeFrame: After first dose of study treatment (pre-dose, 2 hours, 336 hours, 672 hours post dose) and after last dose (pre-dose, 2 hours, 336 hours, 672 hours, 1344 hours, 2016 hours and 3360 hours post dose).
measure: Ianalumab PK parameter - AUCtau
timeFrame: After first dose of study treatment (pre-dose, 2 hours, 336 hours, 672 hours post dose) and after last dose (pre-dose, 2 hours, 336 hours, 672 hours, 1344 hours, 2016 hours and 3360 hours post dose).
measure: Ianalumab PK parameter - Accumulation ratio Racc
timeFrame: After last dose (pre-dose, 2 hours, 336 hours, 672 hours, 1344 hours, 2016 hours and 3360 hours post dose).
measure: Ianalumab PK parameter - Cmax
timeFrame: After first dose of study treatment (pre-dose, 2 hours, 336 hours, 672 hours post dose) and after last dose (pre-dose, 2 hours, 336 hours, 672 hours, 1344 hours, 2016 hours and 3360 hours post dose).
measure: Ianalumab PK parameter - Tmax
timeFrame: After first dose of study treatment (pre-dose, 2 hours, 336 hours, 672 hours post dose) and after last dose (pre-dose, 2 hours, 336 hours, 672 hours, 1344 hours, 2016 hours and 3360 hours post dose).
measure: Immunogenicity of ianalumab
timeFrame: Randomization to end of study (up to 39 months after randomization of last patient)
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado Anschutz
state: Colorado
city: Margate
country: United States
facility: Napa Research
state: Florida
city: Evanston
country: United States
facility: NorthShore University Health System
state: Illinois
city: Fort Wayne
country: United States
facility: Parkview Research Center
state: Indiana
city: Farmington Hills
country: United States
facility: Michigan Center of Medical Research
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota Med Center
state: Minnesota
city: Florham Park
country: United States
facility: Summit Health
state: New Jersey
city: Mullica Hill
country: United States
facility: Inspira Medical Cent Mullica Hill
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Greenville
country: United States
facility: Brody School of Medicine
state: North Carolina
city: Canton
country: United States
facility: Gabrail Cancer Center
state: Ohio
city: Dayton
country: United States
facility: STAT Research Inc
state: Ohio
city: Dallas
country: United States
facility: Texas Oncology-Baylor Scott and White
state: Texas
city: Houston
country: United States
facility: Baylor College Of Medicine
state: Texas
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Center
state: Washington
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Ciudad Autonoma de Bs As
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Buenos aires
country: Argentina
facility: Novartis Investigative Site
city: Canberra
country: Australia
facility: Novartis Investigative Site
state: Australian Capital Territory
city: Fitzroy
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Melbourne
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Guangzhou
country: China
facility: Novartis Investigative Site
state: Guangdong
city: Wuhan
country: China
facility: Novartis Investigative Site
state: Hubei
city: Suzhou
country: China
facility: Novartis Investigative Site
state: Jiangsu
city: Kunming
country: China
facility: Novartis Investigative Site
state: Yunnan
city: Hangzhou
country: China
facility: Novartis Investigative Site
state: Zhejiang
city: Dalian
country: China
facility: Novartis Investigative Site
city: Tianjin
country: China
facility: Novartis Investigative Site
city: Tianjin
country: China
facility: Novartis Investigative Site
city: Blois Cedex
country: France
facility: Novartis Investigative Site
city: Caen
country: France
facility: Novartis Investigative Site
city: Creteil
country: France
facility: Novartis Investigative Site
city: Le Mans
country: France
facility: Novartis Investigative Site
city: Lille
country: France
facility: Novartis Investigative Site
city: Nantes
country: France
facility: Novartis Investigative Site
city: Nice
country: France
facility: Novartis Investigative Site
city: Toulouse
country: France
facility: Novartis Investigative Site
city: Vandoeuvre Les Nancy
country: France
facility: Novartis Investigative Site
city: Frankfurt am Main
country: Germany
facility: Novartis Investigative Site
state: Hessen
city: Dresden
country: Germany
facility: Novartis Investigative Site
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Giessen
country: Germany
facility: Novartis Investigative Site
city: Greifswald
country: Germany
facility: Novartis Investigative Site
city: Hannover
country: Germany
facility: Novartis Investigative Site
city: Debrecen
country: Hungary
facility: Novartis Investigative Site
city: Madurai
country: India
facility: Novartis Investigative Site
state: TamilNadu
city: Hyderabad
country: India
facility: Novartis Investigative Site
state: Telangana
city: Lucknow
country: India
facility: Novartis Investigative Site
state: Uttar Pradesh
city: New Delhi
country: India
facility: Novartis Investigative Site
city: Afula
country: Israel
facility: Novartis Investigative Site
city: Kfar Saba
country: Israel
facility: Novartis Investigative Site
city: Petach Tikva
country: Israel
facility: Novartis Investigative Site
city: Zerifin
country: Israel
facility: Novartis Investigative Site
city: Avellino
country: Italy
facility: Novartis Investigative Site
state: AV
city: Bari
country: Italy
facility: Novartis Investigative Site
state: BA
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Bassano Del Grappa
country: Italy
facility: Novartis Investigative Site
state: Vicenza
city: Novara
country: Italy
facility: Novartis Investigative Site
city: Narita
country: Japan
facility: Novartis Investigative Site
state: Chiba
city: Matsuyama-city
country: Japan
facility: Novartis Investigative Site
state: Ehime
city: Fukuoka city
country: Japan
facility: Novartis Investigative Site
state: Fukuoka
city: Gifu-city
country: Japan
facility: Novartis Investigative Site
state: Gifu
city: Kobe
country: Japan
facility: Novartis Investigative Site
state: Hyogo
city: Isehara
country: Japan
facility: Novartis Investigative Site
state: Kanagawa
city: Suita
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Itabashi-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Shinjuku Ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Aomori
country: Japan
facility: Novartis Investigative Site
city: Yamagata
country: Japan
facility: Novartis Investigative Site
city: Kuching
country: Malaysia
facility: Novartis Investigative Site
state: Sarawak
city: Johor Bahru
country: Malaysia
facility: Novartis Investigative Site
city: Kuala Lumpur
country: Malaysia
facility: Novartis Investigative Site
city: Penang
country: Malaysia
facility: Novartis Investigative Site
city: Pulau Pinang
country: Malaysia
facility: Novartis Investigative Site
city: Selangor
country: Malaysia
facility: Novartis Investigative Site
city: Bucuresti
country: Romania
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Murcia
country: Spain
facility: Novartis Investigative Site
city: Taoyuan
country: Taiwan
facility: Novartis Investigative Site
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Chiang Mai
country: Thailand
facility: Novartis Investigative Site
city: Birmingham
country: United Kingdom
facility: Novartis Investigative Site
city: Leeds
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: