Study of Ianalumab Versus Placebo in Addition to First-line Corticosteroids in Primary Immune Thrombocytopenia (ITP)

Primary Immune Thrombocytopenia (ITP) Clinical Trial

— VAYHIT1  

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05653349
• Other study ID #: CVAY736I12301
• Status: Recruiting
• Phase: Phase 3
• Start date: March 6, 2023
• Est. completion date: February 4, 2028

Study information

• Verified date: March 2024
• Source: Novartis
• Contact: Novartis Pharmaceuticals
• Phone: 1-888-669-6682
• Email: novartis.email[@]novartis.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 225
• Est. completion date: February 4, 2028
• Est. primary completion date: September 25, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 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.

Related Conditions & MeSH terms

• Primary Immune Thrombocytopenia (ITP)
• Purpura, Thrombocytopenic, Idiopathic
• Thrombocytopenia

Intervention

Biological:
• Ianalumab
Intravenous infusion, prepared from concentrate solution

Drug:
• Placebo
Intravenous infusion, prepared from matching placebo
• Corticosteroids
Oral or parental (if clinically justified)

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Buenos aires
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Ciudad Autonoma de Bs As	Buenos Aires
Argentina	Novartis Investigative Site	Tucuman	San Miguel De Tucuman
Australia	Novartis Investigative Site	Canberra	Australian Capital Territory
Australia	Novartis Investigative Site	Clayton	Victoria
Australia	Novartis Investigative Site	Prahran	Victoria
Australia	Novartis Investigative Site	Wooloongabba	Queensland
Austria	Novartis Investigative Site	Innsbruck	Tyrol
Austria	Novartis Investigative Site	Salzburg
Austria	Novartis Investigative Site	Wien
Belgium	Novartis Investigative Site	Brugge
Belgium	Novartis Investigative Site	Leuven
Belgium	Novartis Investigative Site	Roeselare
Bulgaria	Novartis Investigative Site	Plovdiv
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Varna
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Changsha	Hunan
China	Novartis Investigative Site	Chengdu	Sichuan
China	Novartis Investigative Site	Dalian
China	Novartis Investigative Site	Guangzhou	Guangdong
China	Novartis Investigative Site	Hangzhou	Zhejiang
China	Novartis Investigative Site	Hangzhou	Zhejiang
China	Novartis Investigative Site	Jinan
China	Novartis Investigative Site	Kunming	Yunnan
China	Novartis Investigative Site	Nanchang	Jiangxi
China	Novartis Investigative Site	Shenzhen	Guangdong
China	Novartis Investigative Site	Taiyuan	Shanxi
China	Novartis Investigative Site	Tianjin
China	Novartis Investigative Site	Wuhan	Hubei
China	Novartis Investigative Site	Xian	Shaanxi
China	Novartis Investigative Site	Zhengzhou	Henan
Czechia	Novartis Investigative Site	Brno Bohunice	Czech Republic
Czechia	Novartis Investigative Site	Ostrava	Poruba
Czechia	Novartis Investigative Site	Praha
Czechia	Novartis Investigative Site	Praha 10
France	Novartis Investigative Site	Caen	Cedex
France	Novartis Investigative Site	Chambéry cedex
France	Novartis Investigative Site	Le Mans	Cedex 09
France	Novartis Investigative Site	Lille
France	Novartis Investigative Site	Paris
France	Novartis Investigative Site	Rennes
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Frankfurt
Germany	Novartis Investigative Site	Giessen
Germany	Novartis Investigative Site	Greifswald
Germany	Novartis Investigative Site	Hannover
Germany	Novartis Investigative Site	Jena
Hong Kong	Novartis Investigative Site	Hong Kong
Hong Kong	Novartis Investigative Site	New Territories
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Debrecen
India	Novartis Investigative Site	Kolkata	West Bengal
Italy	Novartis Investigative Site	Bologna	BO
Italy	Novartis Investigative Site	Firenze	FI
Italy	Novartis Investigative Site	Roma	RM
Italy	Novartis Investigative Site	Trieste	TS
Italy	Novartis Investigative Site	Vicenza	VI
Japan	Novartis Investigative Site	Chiba
Japan	Novartis Investigative Site	Fukuoka
Japan	Novartis Investigative Site	Gifu shi	Gifu
Japan	Novartis Investigative Site	Iruma-gun	Saitama
Japan	Novartis Investigative Site	Matsumoto-city	Nagano
Japan	Novartis Investigative Site	Okayama city	Okayama
Japan	Novartis Investigative Site	Osaka-city	Osaka
Japan	Novartis Investigative Site	Sapporo	Hokkaido
Japan	Novartis Investigative Site	Shibukawa-city	Gunma
Malaysia	Novartis Investigative Site	Johor Bahru
Malaysia	Novartis Investigative Site	Kuala Lumpur	MYS
Malaysia	Novartis Investigative Site	Kuching	Sarawak
Malaysia	Novartis Investigative Site	Penang
Malaysia	Novartis Investigative Site	Selangor
Mexico	Novartis Investigative Site	Ciudad de Mexico	Mexico CP
Mexico	Novartis Investigative Site	Monterrey	Nuevo Leon
Mexico	Novartis Investigative Site	Morelia	Michoacan
Norway	Novartis Investigative Site	Gralum
Romania	Novartis Investigative Site	Bucharest	District 2
Romania	Novartis Investigative Site	Bucharest
Romania	Novartis Investigative Site	Bucuresti
Singapore	Novartis Investigative Site	Singapore
Singapore	Novartis Investigative Site	Singapore
Singapore	Novartis Investigative Site	Singapore
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Murcia
Spain	Novartis Investigative Site	Salamanca	Castilla Y Leon
Spain	Novartis Investigative Site	Sevilla	Andalucia
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Chiang Mai
Turkey	Novartis Investigative Site	Aydin
Turkey	Novartis Investigative Site	Edirne
Turkey	Novartis Investigative Site	Istanbul
Turkey	Novartis Investigative Site	Istanbul	TUR
Turkey	Novartis Investigative Site	Izmir
Turkey	Novartis Investigative Site	Samsun
United Kingdom	Novartis Investigative Site	Birmingham
United Kingdom	Novartis Investigative Site	Glasgow
United Kingdom	Novartis Investigative Site	Leeds
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	Nottingham
United Kingdom	Novartis Investigative Site	Truro	Cornwall
United States	Oncology Care Associates	Bethesda	Maryland
United States	St Vincent Frontier Cancer Center .	Billings	Montana
United States	Uni of Chi Medi Ctr Hema and Onco Main Centre	Chicago	Illinois
United States	Cleveland Clinic Foundation .	Cleveland	Ohio
United States	Community Cancer Institute	Clovis	California
United States	Texas Oncology-Baylor Res Ins	Dallas	Texas
United States	STAT Research Inc Premier Clin Res LLC STAT Res	Dayton	Ohio
United States	Compassionate Care Res Group Inc	Fountain Valley	California
United States	Clinical Research Alliance Research	Lake Success	New York
United States	Napa Research	Margate	Florida
United States	Texas Oncology	McAllen	Texas
United States	Inspira Medical Cent Mullica Hill	Mullica Hill	New Jersey
United States	Hematology Oncology Association of Rockland	Nyack	New York
United States	Community Cancer Trials of Utah	Ogden	Utah
United States	INTEGRIS Cancer Institute of Oklahoma Integris South West Med Center	Oklahoma City	Oklahoma
United States	Metro Minnesota CCOP Main Site Address Oncology	Saint Louis Park	Minnesota
United States	New Tampa Health	Tampa	Florida
United States	Yuma Regional Medical Center	Yuma	Arizona
Vietnam	Novartis Investigative Site	Hanoi

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Vietnam,  Argentina,  Australia,  Austria,  Belgium,  Bulgaria,  China,  Czechia,  France,  Germany,  Hong Kong,  Hungary,  India,  Italy,  Japan,  Malaysia,  Mexico,  Norway,  Romania,  Singapore,  Spain,  Thailand,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time from randomization to treatment failure (TTF)	Time from randomization until platelet count below 30 G/L, need for a rescue treatment or start of a second-line therapy or death.	Randomization to end of study (up to 39 months after randomization of last patient)
Secondary	Complete Response (CR) rate in each treatment group	Complete Response (CR) rate at each timepoint defined as the proportion of participants with any platelet count of at least 100 G/L in the absence of rescue treatment or new ITP treatment.	Randomization to end of study (up to 39 months after randomization of last patient)
Secondary	Response (R) rate in each treatment group	Response (R) rate at each timepoint defined as the proportion of participants with any platelet count of at least 50 G/L in the absence of rescue treatment or new ITP treatment.	Randomization to end of study (up to 39 months after randomization of last patient)
Secondary	Time to complete response in each treatment group	Time from randomization to date of first complete response.	Randomization to end of study (up to 39 months after randomization of last patient)
Secondary	Duration of response in each treatment group	Time from achievement of complete response to loss of complete response	Randomization to end of study (up to 39 months after randomization of last patient)
Secondary	Stable response at 6 months	Percentage of participants with at least 2 platelet count collected at month 6 (between study dates 107 and 183) and at least 66% of platelet counts qualified as a response	At 6 months
Secondary	Stable response at 1 year	Percentage of participants with at least 2 platelet counts collected at year 1 (between study days 296 and 379) and at least 66% of platelet counts qualified as a response	At 1 year
Secondary	Percentage of participants with bleeding events overall and by World Health Organization (WHO) bleeding scale severity	This is to assess the incidence and severity of bleeding in each treatment arm	Randomization to end of study (up to 39 months after randomization of last patient)
Secondary	Number of participants with bleeding events overall and by World Health Organization (WHO) bleeding scale severity	This is to assess the number and severity of bleeding in each treatment arm	Randomization to end of study (up to 39 months after randomization of last patient)
Secondary	Number of participants receiving rescue treatment (cummulative dose/duration of steroids exposure)	This is to assess the number of participants receiving rescue treatment.	Randomization to end of study (up to 39 months after randomization of last patient)
Secondary	Percentage of participants receiving rescue treatment (cummulative dose/duration of steroids exposure)	This is to assess the need of rescue treatment in each treatment group by percentage.	Randomization to end of study (up to 39 months after randomization of last patient)
Secondary	Cumulative dose/duration of steroids exposure	Duration of exposure to corticosteroids calculated from randomization (first dose) to end of study or last last contact date (if the participant is lost to follow-up).	From screening to end of study (up to 39 months after randomization of last patient)
Secondary	Change from baseline on T scores of the PROMIS SF v1.0 Fatigue 13a	The Patient-Reported Outcomes Measurement Information System (PROMIS) Short Form v1.0 Fatigue 13a includes 13 items that assess fatigue	From screening (baseline) till end of study (up to 39 months after randomization of last patient)
Secondary	Change from baseline in ITP-PAQ domain scores	The ITP-PAQ is a 44 item scale for measuring HRQoL in adults with ITP across ten scales: Symptoms, Bother-Physical Health, Fatigue/Sleep, Activity, Fear, Psychological Health, Work, Social Activity, Women's Reproductive Health, and Overall QoL. Each item is rated on a Likert type scale	From screening (baseline) till end of study (up to 39 months after randomization of last patient)
Secondary	Change from baseline in frequency of CD19+ B cell counts	Post baseline frequency (%within the CD45) of CD19+ B cell counts compare to baseline.	Randomization to end of study (up to 39 months after randomization of last patient)
Secondary	Change from baseline in absolute number of CD19+ B cell counts	Post baseline absolute number of CD19+ B cell counts compare with baseline	Randomization to end of study (up to 39 months after randomization of last patient)
Secondary	Time to first occurrence of B-cell recovery	B-cell recovery, defined as =80% of baseline or =50 cells/µL	Randomization to end of study (up to 39 months after randomized of last patient)
Secondary	Change from baseline in inmmunoglobulins	Change from baseline in immunoglobulin levels	Randomization to end of study (up to 39 months after last randomized patients)
Secondary	PK parameters: AUClast	AUClast: area under the curve from time zero till the last measurable concentration sampling time (tlast)	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)
Secondary	PK parameter: AUCtau	Area under the curve calculated to the end of a dosing interval (tau)	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)
Secondary	PK parameters: Cmax	Maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after single dose administration	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)
Secondary	PK parameters: Tmax	Time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration	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)
Secondary	PK parameters: Accumulation ratio Racc	Accumulation ratio calculated using AUC values obtained between the last and first dose	After last dose (pre-dose, 2, 336, 672, 1344, 2016, 3360 hours post dose)
Secondary	Incidence of anti-ianalumab antibodies in serum (ADA assay) over time	Anti-drug antibodies (ADA) will be evaluated in samples collected from all participants assess the immunogenicity of ianalumab	Up to Week 33
Secondary	Titer of anti-ianalumab antibodies in serum (ADA assay) over time	Anti-drug antibodies (ADA) will be evaluated in samples collected from all participants assess the immunogenicity of ianalumab	Up to Week 33