A Study of Efficacy and Safety of Ianalumab Versus Placebo in Addition to Eltrombopag in Primary Immune Thrombocytopenia Patients Who Failed Steroids (VAYHIT2)

A Phase 3 Randomized, Double-blind Study of Ianalumab (VAY736) Versus Placebo in Addition to Eltrombopag in Patients With Primary Immune Thrombocytopenia (ITP) Who Had an Insufficient Response or Relapsed After First Line Steroid Treatment (VAYHIT2)

The purpose of this study is to evaluate the effect of two different doses of ianalumab added to eltrombopag to prolong Time to Treatment Failure (TTF) in adults with primary ITP who failed previous first-line treatment with steroids.

Study Overview

• Status: Active, not recruiting
• Conditions: Primary Immune Thrombocytopenia
• Intervention / Treatment: Biological: Ianalumab; Drug: Eltrombopag; Drug: Placebo

Detailed Description

This is a multicenter, randomized, double-blinded phase 3 study to assess efficacy and safety of two different doses of ianalumab versus placebo in addition to eltrombopag in adults with primary ITP (platelet count <30 G/L) who failed previous first-line treatment with corticosteroids.

After completion of the screening period, the participants will enter the randomized treatment period (ianalumab/placebo with eltrombopag) followed by the eltrombopag tapering period. Afterwards, all participants will enter the follow-up period to be monitored for efficacy and safety or safety only depending on how the participants responded to the study treatment.

• Study Type: Interventional
• Enrollment (Actual): 152
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • CABA, Argentina, C1181ACH
    • Novartis Investigative Site
• Austria
  • Vienna, Austria, A 1090
    • Novartis Investigative Site
• Belgium
  • Namur
    • Yvoir, Namur, Belgium, 5530
      • Novartis Investigative Site
  • West-Vlaanderen
    • Roeselare, West-Vlaanderen, Belgium, 8800
      • Novartis Investigative Site
• China
  • Beijing, China, 100730
    • Novartis Investigative Site
  • Jinan, China, 250012
    • Novartis Investigative Site
  • Tianjin, China, 300020
    • Novartis Investigative Site
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Novartis Investigative Site
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Novartis Investigative Site
  • Shandong
    • Binzhou, Shandong, China, 256603
      • Novartis Investigative Site
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • Novartis Investigative Site
• Czechia
  • Brno, Czechia, 625 00
    • Novartis Investigative Site
  • Prague, Czechia, 128 08
    • Novartis Investigative Site
  • Prague, Czechia, 100 34
    • Novartis Investigative Site
• France
  • Blois, France, 41000
    • Novartis Investigative Site
  • Le Mans, France, 72000
    • Novartis Investigative Site
• Germany
  • Aachen, Germany, 52074
    • Novartis Investigative Site
  • Bonn, Germany, 53105
    • Novartis Investigative Site
  • Dresden, Germany, 01307
    • Novartis Investigative Site
  • North Rhine-Westphalia
    • Cologne, North Rhine-Westphalia, Germany, 50937
      • Novartis Investigative Site
    • Düsseldorf, North Rhine-Westphalia, Germany, 40225
      • Novartis Investigative Site
  • Saxony
    • Dresden, Saxony, Germany, 01307
      • Novartis Investigative Site
  • Thuringia
    • Jena, Thuringia, Germany, 07740
      • Novartis Investigative Site
• Hungary
  • Budapest, Hungary, H-1083
    • Novartis Investigative Site
  • Hajdu Bihar Megye
    • Debrecen, Hajdu Bihar Megye, Hungary, 4032
      • Novartis Investigative Site
• India
  • Uttarakhand
    • Rishikesh, Uttarakhand, India, 249203
      • Novartis Investigative Site
  • West Bengal
    • Kolkata, West Bengal, India, 700014
      • Novartis Investigative Site
• Italy
  • BO
    • Bologna, BO, Italy, 40138
      • Novartis Investigative Site
  • RM
    • Roma, RM, Italy, 00168
      • Novartis Investigative Site
    • Roma, RM, Italy, 00133
      • Novartis Investigative Site
  • TS
    • Trieste, TS, Italy, 34129
      • Novartis Investigative Site
• Japan
  • Kumamoto, Japan, 860-0008
    • Novartis Investigative Site
  • Aichi-ken
    • Nagoya, Aichi-ken, Japan, 453-8511
      • Novartis Investigative Site
  • Osaka
    • Osaka, Osaka, Japan, 5400006
      • Novartis Investigative Site
    • Suita, Osaka, Japan, 565-0871
      • Novartis Investigative Site
  • Yamanashi
    • Kofu, Yamanashi, Japan, 400-8506
      • Novartis Investigative Site
• Malaysia
  • George Town, Malaysia, 10050
    • Novartis Investigative Site
  • Johor Bahru, Malaysia, 80100
    • Novartis Investigative Site
  • Kuala Selangor, Malaysia, 68000
    • Novartis Investigative Site
  • Pulau Pinang
    • George Town, Pulau Pinang, Malaysia, 10450
      • Novartis Investigative Site
  • Sabah
    • Kota Kinabalu, Sabah, Malaysia, 88586
      • Novartis Investigative Site
  • Selangor
    • Subang Jaya, Selangor, Malaysia, 47500
      • Novartis Investigative Site
• Mexico
  • Coahuila
    • Saltillo, Coahuila, Mexico, 25230
      • Novartis Investigative Site
  • Michoacán
    • Morelia, Michoacán, Mexico, 58260
      • Novartis Investigative Site
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 64460
      • Novartis Investigative Site
• Netherlands
  • Utrecht, Netherlands, 3584 CX
    • Novartis Investigative Site
  • South Holland
    • Leiden, South Holland, Netherlands, 2333 ZA
      • Novartis Investigative Site
• Philippines
  • Makati City, Philippines, 1229
    • Novartis Investigative Site
  • Quezon, Philippines, 1102
    • Novartis Investigative Site
• Romania
  • Timișoara, Romania, 300079
    • Novartis Investigative Site
  • Dolj
    • Craiova, Dolj, Romania, 200136
      • Novartis Investigative Site
• Singapore
  • Singapore, Singapore, 119074
    • Novartis Investigative Site
  • Singapore, Singapore, 169608
    • Novartis Investigative Site
• South Korea
  • Jeollanam, South Korea, 519763
    • Novartis Investigative Site
  • Seoul, South Korea, 06591
    • Novartis Investigative Site
• Spain
  • Salamanca, Spain, 37007
    • Novartis Investigative Site
  • A Coruna
    • Santiago Compostela, A Coruna, Spain, 15706
      • Novartis Investigative Site
• Taiwan
  • Taoyuan, Taiwan, 33305
    • Novartis Investigative Site
• Thailand
  • Bangkok, Thailand, 10700
    • Novartis Investigative Site
  • Chiang Mai, Thailand, 50200
    • Novartis Investigative Site
• Turkey (Türkiye)
  • Izmir, Turkey (Türkiye), 35100
    • Novartis Investigative Site
  • Atakum
    • Samsun, Atakum, Turkey (Türkiye), 55200
      • Novartis Investigative Site
  • Bilkent Cankaya
    • Ankara, Bilkent Cankaya, Turkey (Türkiye), 06800
      • Novartis Investigative Site
  • Efeler
    • Aydin, Efeler, Turkey (Türkiye), 09100
      • Novartis Investigative Site
  • Fatih
    • Istanbul, Fatih, Turkey (Türkiye), 34098
      • Novartis Investigative Site
• United Kingdom
  • London, United Kingdom, W12 0HS
    • Novartis Investigative Site
  • London, United Kingdom, E1 1BB
    • Novartis Investigative Site
  • Oxford, United Kingdom, OX3 7LE
    • Novartis Investigative Site
• United States
  • Arizona
    • Yuma, Arizona, United States, 85349
      • Yuma Regional Medical Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Anschutz
  • Illinois
    • Evanston, Illinois, United States, 60201
      • Northshore University Health System
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center
    • Worcester, Massachusetts, United States, 01665
      • UMass Memorial Medical Center
  • Michigan
    • Farmington Hills, Michigan, United States, 48334
      • Michigan Center of Medical Research
  • Montana
    • Billings, Montana, United States, 59102
      • St Vincent Frontier Cancer Center
  • New York
    • Nyack, New York, United States, 10960
      • Hematology Oncology Association of Rockland
    • The Bronx, New York, United States, 10461
      • Montefiore Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion criteria

1. Male or female patients aged 18 years and older on the day of signing the informed consent.
2. A signed informed consent must be obtained prior to participation in the study.
3. A diagnosis of primary ITP, with insufficient response to, or relapse after a first-line corticosteroid therapy ± IVIG.
4. Patient with platelet count <30G/L (whom eltrombopag is clinically indicated as per physician's discretion) and with no contraindication to receive eltrombopag

Key Exclusion criteria

1. ITP patients who received second-line ITP treatments (other than steroid therapy± IVIG) including splenectomy. However, patients exposed to thrombopoietin receptor agonists (TPO-RAs) for a limited time (max one week) before screening are eligible.
2. Patients with key lab abnormalities and patients with Evans syndrome or any other cytopenia, (patients with low grade anemia related to bleeding or iron deficiency are eligible).
3. Patients with history of clinically significant hematological disorders, or with marked altered hematologic parameters
4. Patients with current or history of life-threatening bleeding
5. Patient that are Human Immunodeficiency Virus (HIV), Hepatitis C Virus (HCV), Hepatitis B surface Antigen (HBsAg)/ Hepatitis B core antibody (HBcAb)-positive. HBcAb-positive patients can be enrolled if HBsAg negative, HBV DNA negative, no pre-existing liver fibrosis is present and antiviral prophylaxis is given
6. Patients with known active or uncontrolled infection requiring systemic treatment during screening period
7. Patients with hepatic impairment
8. Patients with concurrent coagulation disorders and/or receiving antiplatelet or anticoagulant medication with an exemption of low dose of acetylsalicylic acid (≤150 mg daily)
9. Nursing (breast feeding) or pregnant women

Other protocol-defined inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment arm 1; Participants will receive eltrombopag and ianalumab lower dose	Biological: Ianalumab; Concentrate for solution for infusion for intravenous use; Other Names: VAY736; Drug: Eltrombopag; Film-coated tablet for oral use; Other Names: ETB115
Experimental: Treatment arm 2; Participants will receive eltrombopag and ianalumab higher dose	Biological: Ianalumab; Concentrate for solution for infusion for intravenous use; Other Names: VAY736; Drug: Eltrombopag; Film-coated tablet for oral use; Other Names: ETB115
Placebo Comparator: Treatment arm 3; Participants will receive eltrombopag and placebo	Drug: Eltrombopag; Film-coated tablet for oral use; Other Names: ETB115; Drug: Placebo; Concentrate for solution for infusion for intravenous use.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time from randomization until treatment failure	Time from randomization until treatment failure is defined as the time from randomization date until the first of the following events indicative of treatment failure: platelet count below 30 G/L; start of a new ITP treatment; need for a rescue treatment; ineligibility to taper or inability to discontinue eltrombopag; death	Randomization to until end of study (up to 39 months after randomization of last participant)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Response rate at each timepoint	Percentage of participants with any platelet count of at least 100 G/L in the absence of rescue treatment or new ITP treatment	Randomization to until end of study (up to 39 months after randomization of last participant)
Response rate at each timepoint	Percentage of participants with any platelet count of at least 50 G/L in the absence of rescue treatment or new ITP treatment	Randomization to until end of study (up to 39 months after randomization of last participant)
Best response rate across all timepoints	Percentage of participants with a best response rate of either response or complete response	Randomization to until end of study (up to 39 months after randomization of last participant)
Time to first response/time to first complete response	Time from randomization to date of first response and time from randomization to date of first complete response	Time from randomization up to the longest observed treatment period duration
Rate of participants who successfully taper and discontinue eltrombopag in each treatment arm	Probability to be treatment failure-free (as defined for the primary efficacy endpoint)	up to week 24
Percentage of participants with bleeding events according to World Health Organization (WHO)	Percentage of participants reporting bleeding events according to WHO bleeding scale	Randomization to until end of study (up to 39 months after randomization of last participant)
Number of participants receiving rescue treatment	Number of participants who are in need of rescue treatment in each treatment arm	Randomization to until end of study (up to 39 months after randomization of last participant)
Percentage of participants receiving rescue treatment	Percentage of participants who are in need of rescue treatment	Randomization to until end of study (up to 39 months after randomization of last participant)
Change from baseline in the frequency of CD19+ B-cell counts	Post-baseline frequency of CD19+ B-cell counts (percentage within CD45) compared to baseline	Randomization to until end of study (up to 39 months after randomization of last participant)
Change from baseline in the absolute number of CD19+ B-cell counts	Post-baseline absolute number of CD19+ B-cell counts compared to baseline	Randomization to until end of study (up to 39 months after randomization of last participant)
Change from baseline in ITP PAQ domain scores of symptoms, fatigue, bother (uncomfortable), activity	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, overall QoL. Each item is rated on a Likert type scale. Each scale is scored from 0 to 100. Higher scores represent better HRQoL.	From screening (baseline) until end of study (up 39 months after randomization of last participant)
Time to first occurence of B-cell recovery defined as ≥80% of baseline ≥50 cells/µL	Time to B-cell recovery defined as ≥80% of baseline or ≥50 cells/µL	Randomization to until end of study (up to 39 months after randomization of last participant)
Change from baseline in immunoglobulins	Change from baseline in immunoglobulin levels	Randomization to until end of study (up to 39 months after randomization of last participant)
Incidence of anti-ianalumab antibodies in serum (ADA assay) over time	Anti-drug antibodies (ADA) will be evaluated in samples collected from all participants assessing the immunogenicity of ianalumab	up to week 33
Titer of anti-ianalumab antibodies in serum (ADA assay) over time	Anti-drug antibodies (ADA) will be evaluated in samples collected from all participants assessing the immunogenicity of ianalumab	up to week 33
Duration of complete response	Time from achievement of complete response to loss of complete response stable response at 1 year period	Randomization to end of study (up to 39 months after randomization of last participant)
Change from baseline on T-score 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 in adults.	From screening (baseline) until end of study (up 39 months after randomization of last participant)
PK parameters: AUClast	AUClast: Area under the curve from time zero to the last measurable concentration sampling time (tlast)	After first dose (pre-dose, EOI, 168, 336 and 504 hours post dose) and after last dose (pre-dose, EOI, 336, 672, 2016, 3360 hours post dose)
PK parameters: AUCtau	AUCtau: Area under the curve calculated to the end of a dosing interval (tau)	After first dose (pre-dose, EOI, 168, 336 and 504 hours post dose) and after last dose (pre-dose, EOI, 336, 672, 2016, 3360 hours post dose)
PK parameters: Cmax	Maximum (peak) observed plasma, blood, serum or other body fluid drug concentration	After first dose (pre-dose, EOI, 168, 336 and 504 hours post dose) and after last dose (pre-dose, EOI, 336, 672, 2016, 3360 hours post dose)
PK parameters: Tmax	Time to reach maximum (peak) observed plasma, blood, serum or other body fluid drug concentration	After first dose (pre-dose, EOI, 168, 336 and 504 hours post dose) and after last dose (pre-dose, EOI, 336, 672, 2016, 3360 hours post dose)
PK parameters: Accumulation ratio Racc	Accumulation ratio calculated using AUC values obtained after the last and first dose	After last dose (pre-dose, EOI, 336, 672, 2016, 3360 hours post dose)
Duration of response	Time from achievement of response to treatment failure.	Randomization to until end of study (up to 39 months after randomization of last participant)
Stable response at 1 year	Percentage of participants with at least 2 platelet count collected at year 1 (between study days 296 and 379 and at least 66% of platelet counts qualified as a response).	At 1 year
Stable response at 6 months (Key Secondary Endpoint)	Percentage of participants with at least 3 platelet count collected at month 6 (between study days 121 and 183 and at least 75% of platelet counts qualified as a response).	At 6 months

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Cuker A, Stauch T, Cooper N, Al-Samkari H, Michel M, Ghanima W, Urban P, Fronczek J, Foster M, Weill M, Zhang L, Hou M, Zander T, Sharif A, Sun J, Nath UK, Schutgens R, Rossi E, Deleu L, Cervinek L, Yoon JH, Chang H, Ruchutrakool T, Iino M, Goto T, Zaja F; VAYHIT2 Investigators. Ianalumab plus Eltrombopag in Immune Thrombocytopenia. N Engl J Med. 2026 Apr 16;394(15):1503-1513. doi: 10.1056/NEJMoa2515168. Epub 2025 Dec 9.

Study record dates

Study Major Dates

• Study Start (Actual): February 2, 2023
• Primary Completion (Actual): June 19, 2025
• Study Completion (Estimated): April 8, 2028

Study Registration Dates

• First Submitted: November 23, 2022
• First Submitted That Met QC Criteria: December 14, 2022
• First Posted (Actual): December 16, 2022

Study Record Updates

• Last Update Posted (Actual): May 27, 2026
• Last Update Submitted That Met QC Criteria: May 25, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: VAY736; eltrombopag; B-cell depletion; ianalumab; B-cell Activating Factor Receptor (BAFF-R) blockade; Primary immune thrombocytopenia (ITP),
• Additional Relevant MeSH Terms: Cytopenia; Pathologic Processes; Autoimmune Diseases; Immune System Diseases; Hemorrhage; Skin Manifestations; Hematologic Diseases; Blood Coagulation Disorders; Hemorrhagic Disorders; Blood Platelet Disorders; Thrombotic Microangiopathies; Purpura, Thrombocytopenic; Purpura; Thrombocytopenia; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Hemic and Lymphatic Diseases; Purpura, Thrombocytopenic, Idiopathic; Substandard Drugs; Pharmaceutical Preparations; eltrombopag; ianalumab
• Other Study ID Numbers: CVAY736Q12301; 2024-512890-28-00 (Other Identifier: EU CTIS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No