Clinical trial NCT05653349: Study of Ianalumab Versus Placebo in Addition to First-line Corticosteroids in Primary Immune Thrombocytopenia (ITP)
Official title: A Phase III, Randomized, Double-blind Study of Ianalumab (VAY736) Versus Placebo in Addition to First-line Corticosteroids in Primary Immune Thrombocytopenia (VAYHIT1)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Primary Immune Thrombocytopenia (ITP)
Keywords: Primary immune thrombocytopenia (ITP)
ianalumab
VAY736
B-cell depletion
B-cell Activating Factor Receptor (BAFF-R) blockade
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2022-12-16
Enrollment: 225
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 the effect of two different doses of ianalumab versus placebo in addition to first-line corticosteroids in maintaining platelet count ≥30 G/L in adult participants with primary ITP.

Detailed description: This is a multi-center, randomized, double-blind Phase 3 study to assess the efficacy and safety of two different doses of ianalumab compared to placebo in adults with primary ITP (platelets count \<30 G/L) who require first-line standard-of-care corticosteroids.

After completion of the screening period, the participants will enter the randomized treatment period (ianalumab/placebo with standard of care corticosteroids).

After the treatment period, all participants will enter the follow-up period to be monitored for efficacy and safety or safety only depending on how they respond to the study treatment.

Eligibility criteria: Inclusion Criteria:

* Signed informed consent prior to participation in the study.
* Male or female participants aged 18 years and older on the day of signing informed consent
* Primary ITP diagnosed within 3 months before initiating first-line ITP therapy (corticosteroids, IVIG)
* Platelet count below 30 G/L before starting any first-line ITP therapy (corticosteroids, IVIG)
* Response (platelet count \>=50 G/L) to corticosteroids (+/- IVIG) at any time prior to randomization. Note: Platelet count measured within 7 days of platelet transfusion will not be considered as response.

Key Exclusion Criteria:

* Evans syndrome or any other cytopenia (patients with low grade anemia related to bleeding or iron deficiency are eligible)
* Current life-threatening bleeding
* Previous ITP treatment, including splenectomy, except for corticosteroids and/or IVIG initiated as first-line therapy for up to 28 days before randomization and rescue corticosteroids and/or IVIG given prior to confirmed diagnosis of primary ITP .
* Prior use of B-cell depleting therapy (e.g., rituximab).
* Absolute neutrophil count below 1.0 G/L at randomization
* Participants with concurrent coagulation disorders and/or receiving anti-platelet or anticoagulant medication with an exemption of low dose of acetylsalicylic acid

Other protocol-defined Inclusion/Exclusion may apply.

Primary outcomes:
measure: Time from randomization to treatment failure (TTF)
timeFrame: Randomization to end of study (up to 39 months after randomization of last patient)
Secondary outcomes:
measure: Complete Response (CR) rate in each treatment group
timeFrame: Randomization to end of study (up to 39 months after randomization of last patient)
measure: Response (R) rate in each treatment group
timeFrame: Randomization to end of study (up to 39 months after randomization of last patient)
measure: Time to complete response in each treatment group
timeFrame: Randomization to end of study (up to 39 months after randomization of last patient)
measure: Duration of response in each treatment group
timeFrame: Randomization to end of study (up to 39 months after randomization of last patient)
measure: Stable response at 6 months
timeFrame: At 6 months
measure: Stable response at 1 year
timeFrame: At 1 year
measure: Percentage of participants with bleeding events overall and by World Health Organization (WHO) bleeding scale severity
timeFrame: Randomization to end of study (up to 39 months after randomization of last patient)
measure: Number of participants with bleeding events overall and by World Health Organization (WHO) bleeding scale severity
timeFrame: Randomization to end of study (up to 39 months after randomization of last patient)
measure: Number of participants receiving rescue treatment (cummulative dose/duration of steroids exposure)
timeFrame: Randomization to end of study (up to 39 months after randomization of last patient)
measure: Percentage of participants receiving rescue treatment (cummulative dose/duration of steroids exposure)
timeFrame: Randomization to end of study (up to 39 months after randomization of last patient)
measure: Cumulative dose/duration of steroids exposure
timeFrame: From screening to end of study (up to 39 months after randomization of last patient)
measure: Change from baseline on T scores of the PROMIS SF v1.0 Fatigue 13a
timeFrame: From screening (baseline) till end of study (up to 39 months after randomization of last patient)
measure: Change from baseline in ITP-PAQ domain scores
timeFrame: From screening (baseline) till end of study (up to 39 months after randomization of last patient)
measure: Change from baseline in frequency of CD19+ B cell counts
timeFrame: Randomization to end of study (up to 39 months after randomization of last patient)
measure: Change from baseline in 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
timeFrame: Randomization to end of study (up to 39 months after randomized of last patient)
measure: Change from baseline in inmmunoglobulins
timeFrame: Randomization to end of study (up to 39 months after last randomized patients)
measure: PK parameters: AUClast
timeFrame: After first dose (pre-dose, 2, 168, 336 and 504 hours post dose) and after last dose (pre-dose, 2, 336, 672, 1344, 2016, 3360 hours post dose)
measure: PK parameter: AUCtau
timeFrame: After first dose (pre-dose, 2, 168, 336 and 504 hours post dose) and after last dose (pre-dose, 2, 336, 672, 1344, 2016, 3360 hours post dose)
measure: PK parameters: Cmax
timeFrame: After first dose (pre-dose, 2, 168, 336 and 504 hours post dose) and after last dose (pre-dose, 2, 336, 672, 1344, 2016, 3360 hours post dose)
measure: PK parameters: Tmax
timeFrame: After first dose (pre-dose, 2, 168, 336 and 504 hours post dose) and after last dose (pre-dose, 2, 336, 672, 1344, 2016, 3360 hours post dose)
measure: PK parameters: Accumulation ratio Racc
timeFrame: After last dose (pre-dose, 2, 336, 672, 1344, 2016, 3360 hours post dose)
measure: Incidence of anti-ianalumab antibodies in serum (ADA assay) over time
timeFrame: Up to Week 33
measure: Titer of anti-ianalumab antibodies in serum (ADA assay) over time
timeFrame: Up to Week 33
Other outcomes:
Locations:
city: Yuma
country: United States
facility: Yuma Regional Medical Center
state: Arizona
city: Clovis
country: United States
facility: Community Cancer Institute
state: California
city: Fountain Valley
country: United States
facility: Compassionate Care Res Group Inc
state: California
city: Aurora
country: United States
facility: University of Colorado Anschutz
state: Colorado
city: Margate
country: United States
facility: Napa Research
state: Florida
city: Tampa
country: United States
facility: New Tampa Health
state: Florida
city: Chicago
country: United States
facility: Uni of Chi Medi Ctr Hema and Onco
state: Illinois
city: Fort Wayne
country: United States
facility: Parkview Research Center
state: Indiana
city: Bethesda
country: United States
facility: Oncology Care Associates
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Farmington Hills
country: United States
facility: Michigan Center of Medical Research
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: Saint Louis Park
country: United States
facility: Metro Minnesota CCOP
state: Minnesota
city: Billings
country: United States
facility: St Vincent Frontier Cancer Center
state: Montana
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: Lake Success
country: United States
facility: Clinical Research Alliance
state: New York
city: Nyack
country: United States
facility: Hematology Oncology Association of Rockland
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Dayton
country: United States
facility: STAT Research Inc
state: Ohio
city: Oklahoma City
country: United States
facility: INTEGRIS Cancer Institute of Oklahoma
state: Oklahoma
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Dallas
country: United States
facility: Texas Oncology-Baylor Res Ins
state: Texas
city: McAllen
country: United States
facility: Texas Oncology
state: Texas
city: San Antonio
country: United States
facility: Mays Cancer Ctr Uthsa Mdacc
state: Texas
city: Ogden
country: United States
facility: Community Cancer Trials of Utah
state: Utah
city: Bahia Blanca
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
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: Tucuman
country: Argentina
facility: Novartis Investigative Site
state: San Miguel De Tucuman
city: Buenos aires
country: Argentina
facility: Novartis Investigative Site
city: Cordoba
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facility: Novartis Investigative Site
city: Canberra
country: Australia
facility: Novartis Investigative Site
state: Australian Capital Territory
city: Wooloongabba
country: Australia
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state: Queensland
city: Clayton
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facility: Novartis Investigative Site
state: Victoria
city: Melbourne
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state: Victoria
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state: Tyrol
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city: Varna
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city: Beijing
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state: Beijing
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city: Guangzhou
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state: Guangdong
city: Shenzhen
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state: Guangdong
city: Luoyang
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facility: Novartis Investigative Site
state: Henan
city: Zhengzhou
country: China
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state: Henan
city: Wuhan
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state: Hubei
city: Changsha
country: China
facility: Novartis Investigative Site
state: Hunan
city: Changzhou
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facility: Novartis Investigative Site
state: Jiangsu
city: Nanchang
country: China
facility: Novartis Investigative Site
state: Jiangxi
city: Xian
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facility: Novartis Investigative Site
state: Shaanxi
city: Taiyuan
country: China
facility: Novartis Investigative Site
state: Shanxi
city: Chengdu
country: China
facility: Novartis Investigative Site
state: Sichuan
city: Kunming
country: China
facility: Novartis Investigative Site
state: Yunnan
city: Hangzhou
country: China
facility: Novartis Investigative Site
state: Zhejiang
city: Hangzhou
country: China
facility: Novartis Investigative Site
state: Zhejiang
city: Bengbu
country: China
facility: Novartis Investigative Site
city: Dalian
country: China
facility: Novartis Investigative Site
city: Jinan
country: China
facility: Novartis Investigative Site
city: Shijiazhuang
country: China
facility: Novartis Investigative Site
city: Tianjin
country: China
facility: Novartis Investigative Site
city: Ostrava
country: Czechia
facility: Novartis Investigative Site
state: Poruba
city: Brno Bohunice
country: Czechia
facility: Novartis Investigative Site
city: Praha 10
country: Czechia
facility: Novartis Investigative Site
city: Praha
country: Czechia
facility: Novartis Investigative Site
city: Caen
country: France
facility: Novartis Investigative Site
city: Chambery cedex
country: France
facility: Novartis Investigative Site
city: Le Mans
country: France
facility: Novartis Investigative Site
city: Lille
country: France
facility: Novartis Investigative Site
city: Paris
country: France
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city: Rennes
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facility: Novartis Investigative Site
city: Frankfurt am Main
country: Germany
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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
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city: Hannover
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city: Jena
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city: Hong Kong
country: Hong Kong
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city: Debrecen
country: Hungary
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state: Gujarat
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country: India
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city: Rishikesh
country: India
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state: Uttarakhand
city: Kolkata
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state: West Bengal
city: Bologna
country: Italy
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state: BO
city: Firenze
country: Italy
facility: Novartis Investigative Site
state: FI
city: Roma
country: Italy
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state: RM
city: Trieste
country: Italy
facility: Novartis Investigative Site
state: TS
city: Vicenza
country: Italy
facility: Novartis Investigative Site
state: VI
city: Nagakute-city
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Gifu shi
country: Japan
facility: Novartis Investigative Site
state: Gifu
city: Shibukawa-city
country: Japan
facility: Novartis Investigative Site
state: Gunma
city: Sapporo
country: Japan
facility: Novartis Investigative Site
state: Hokkaido
city: Matsumoto-city
country: Japan
facility: Novartis Investigative Site
state: Nagano
city: Okayama city
country: Japan
facility: Novartis Investigative Site
state: Okayama
city: Osaka-city
country: Japan
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state: Osaka
city: Iruma-gun
country: Japan
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state: Saitama
city: Chiba
country: Japan
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city: Fukuoka
country: Japan
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city: Kuching
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country: Malaysia
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city: Kuala Lumpur
country: Malaysia
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city: Penang
country: Malaysia
facility: Novartis Investigative Site
city: Selangor
country: Malaysia
facility: Novartis Investigative Site
city: Mexico
country: Mexico
facility: Novartis Investigative Site
state: Distrito Federal
city: Ciudad De Mexico
country: Mexico
facility: Novartis Investigative Site
state: Mexico CP
city: Morelia
country: Mexico
facility: Novartis Investigative Site
state: Michoacan
city: Monterrey
country: Mexico
facility: Novartis Investigative Site
state: Nuevo Leon
city: Gralum
country: Norway
facility: Novartis Investigative Site
city: Bucharest
country: Romania
facility: Novartis Investigative Site
state: District 2
city: Bucharest
country: Romania
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: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Sevilla
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Salamanca
country: Spain
facility: Novartis Investigative Site
state: Castilla Y Leon
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Murcia
country: Spain
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: Istanbul
country: Turkey
facility: Novartis Investigative Site
state: TUR
city: Aydin
country: Turkey
facility: Novartis Investigative Site
city: Edirne
country: Turkey
facility: Novartis Investigative Site
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
city: Izmir
country: Turkey
facility: Novartis Investigative Site
city: Samsun
country: Turkey
facility: Novartis Investigative Site
city: Truro
country: United Kingdom
facility: Novartis Investigative Site
state: Cornwall
city: Birmingham
country: United Kingdom
facility: Novartis Investigative Site
city: Glasgow
country: United Kingdom
facility: Novartis Investigative Site
city: Leeds
country: United Kingdom
facility: Novartis Investigative Site
city: Liverpool
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
city: Nottingham
country: United Kingdom
facility: Novartis Investigative Site
city: Southampton
country: United Kingdom
facility: Novartis Investigative Site
city: Hanoi
country: Vietnam
facility: Novartis Investigative Site
city: Ho Chi Minh
country: Vietnam
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: