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

• ClinicalTrials.gov Identifier: NCT05653219
• Recruitment Status: Recruiting
• First Posted: December 16, 2022
• Last Update Posted: May 26, 2023
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Primary Immune Thrombocytopenia	Biological: Ianalumab; Drug: Eltrombopag; Drug: Placebo	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 150 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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)
• Actual Study Start Date: February 2, 2023
• Estimated Primary Completion Date: June 6, 2025
• Estimated Study Completion Date: February 2, 2028

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Time from randomization until treatment failure [ Time Frame: Randomization to until end of study (up to 39 months after randomization of last participant) ]

   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

Secondary Outcome Measures :

1. Complete Response rate at each timepoint [ Time Frame: Randomization to until end of study (up to 39 months after randomization of last participant) ]
   Percentage of participants with any platelet count of at least 100 G/L in the absence of rescue treatment or new ITP treatment
2. Response rate at each timepoint [ Time Frame: Randomization to until end of study (up to 39 months after randomization of last participant) ]
   Percentage of participants with any platelet count of at least 50 G/L in the absence of rescue treatment or new ITP treatment
3. Best response rate across all timepoints [ Time Frame: Randomization to until end of study (up to 39 months after randomization of last participant) ]
   Percentage of participants with a best response rate of either response or complete response
4. Time to first response/time to first complete response [ Time Frame: Time from randomization up to the longest observed treatment period duration ]
   Time from randomization to date of first response and time from randomization to date of first complete response
5. Duration of response [ Time Frame: Randomization to until end of study (up to 39 months after randomization of last participant) ]
   Time from achievement of response to treatment failure
6. Duration of complete response [ Time Frame: Randomization to end of study (up to 39 months after randomization of last participant) ]
   Time from achievement of complete response to loss of complete response
7. Rate of participants who successfully taper and discontinue eltrombopag in each treatment arm [ Time Frame: up to week 24 ]
   Probability to be treatment failure-free (as defined for the primary efficacy endpoint)
8. Percentage of participants with bleeding events according to World Health Organization (WHO) [ Time Frame: Randomization to until end of study (up to 39 months after randomization of last participant) ]
   Percentage of participants reporting bleeding events according to WHO bleeding scale
9. Number of participants receiving rescue treatment [ Time Frame: Randomization to until end of study (up to 39 months after randomization of last participant) ]
   Number of participants who are in need of rescue treatment in each treatment arm
10. Percentage of participants receiving rescue treatment [ Time Frame: Randomization to until end of study (up to 39 months after randomization of last participant) ]
    Percentage of participants who are in need of rescue treatment
11. Change from baseline in the frequency of CD19+ B-cell counts [ Time Frame: Randomization to until end of study (up to 39 months after randomization of last participant) ]
    Post-baseline frequency of CD19+ B-cell counts (percentage within CD45) compared to baseline
12. Change from baseline in the absolute number of CD19+ B-cell counts [ Time Frame: Randomization to until end of study (up to 39 months after randomization of last participant) ]
    Post-baseline absolute number of CD19+ B-cell counts compared to baseline
13. Change from baseline on total score of the PROMIS SF v1.0 Fatigue 13a [ Time Frame: From screening (baseline) until end of study (up 39 months after randomization of last participant) ]
    The Patient-Reported Outcomes Measurement Information System (PROMIS) Short Form v1.0 Fatigue 13a includes 13 items that assess fatigue in adults.
14. Change from baseline in ITP PAQ domain scores of symptoms, fatigue, bother (uncomfortable), activity [ Time Frame: From screening (baseline) until end of study (up 39 months after randomization of last participant) ]
    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.
15. Time to first occurence of B-cell recovery defined as ≥80% of baseline ≥50 cells/µL [ Time Frame: Randomization to until end of study (up to 39 months after randomization of last participant) ]
    Time to B-cell recovery defined as ≥80% of baseline or ≥50 cells/µL
16. Change from baseline in immunoglobulins [ Time Frame: Randomization to until end of study (up to 39 months after randomization of last participant) ]
    Change from baseline in immunoglobulin levels
17. PK parameters: AUClast [ Time Frame: 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) ]
    AUClast: Area under the curve from time zero to the last measurable concentration sampling time (tlast)
18. PK parameters: AUCtau [ Time Frame: 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) ]
    AUCtau: Area under the curve calculated to the end of a dosing interval (tau)
19. PK parameters: Cmax [ Time Frame: 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) ]
    Maximum (peak) observed plasma, blood, serum or other body fluid drug concentration
20. PK parameters: Tmax [ Time Frame: 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) ]
    Time to reach maximum (peak) observed plasma, blood, serum or other body fluid drug concentration
21. PK parameters: Accumulation ratio Racc [ Time Frame: After last dose (pre-dose, 2, 336, 672, 1344, 2016, 3360 hours post dose) ]
    Accumulation ratio calculated using AUC values obtained after the last and first dose
22. Incidence of anti-ianalumab antibodies in serum (ADA assay) over time [ Time Frame: up to week 33 ]
    Anti-drug antibodies (ADA) will be evaluated in samples collected from all participants assessing the immunogenicity of ianalumab
23. Titer of anti-ianalumab antibodies in serum (ADA assay) over time [ Time Frame: up to week 33 ]
    Anti-drug antibodies (ADA) will be evaluated in samples collected from all participants assessing the immunogenicity of ianalumab

Eligibility Criteria

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

Criteria

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. Platelet count <30 G/L and assessed need for treatment (per physician's discretion).

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
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
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
9. Female patients who are pregnant or nursing

Other protocol-defined inclusion/exclusion criteria may apply.

Contacts and Locations

Contacts

Contact: Novartis Pharmaceuticals; 1-888-669-6682; novartis.email@novartis.com

Contact: Novartis Pharmaceuticals; +41613241111

Locations

United States, Utah

Community Cancer Trials of Utah; Recruiting

Ogden, Utah, United States, 84405

Contact: Sibian Torres 801-689-3909 Sibian@communitycancertrials.com

Principal Investigator: Carl Gray

Austria

Novartis Investigative Site; Recruiting

Linz, Austria, 4010

Belgium

Novartis Investigative Site; Recruiting

Roeselare, Belgium, 8800

Novartis Investigative Site; Recruiting

Yvoir, Belgium, 5530

China, Guangdong

Novartis Investigative Site; Recruiting

Guangzhou, Guangdong, China, 510515

China, Hubei

Novartis Investigative Site; Recruiting

Wuhan, Hubei, China, 430022

China, Shandong

Novartis Investigative Site; Recruiting

Binzhou, Shandong, China, 256603

China, Tianjin

Novartis Investigative Site; Recruiting

Tianjin, Tianjin, China, 300020

China

Novartis Investigative Site; Recruiting

Ji Nan, China, 250012

Czechia

Novartis Investigative Site; Recruiting

Brno Bohunice, Czech Republic, Czechia, 625 00

Novartis Investigative Site; Recruiting

Praha 10, Czechia, 100 34

Novartis Investigative Site; Recruiting

Praha, Czechia, 12808

Germany

Novartis Investigative Site; Recruiting

Dresden, Germany, 01307

Novartis Investigative Site; Recruiting

Greifswald, Germany, 17475

Novartis Investigative Site; Recruiting

Jena, Germany, 07740

Hungary

Novartis Investigative Site; Recruiting

Budapest, Hungary, 1085

Novartis Investigative Site; Recruiting

Debrecen, Hungary, 4032

Japan

Novartis Investigative Site; Recruiting

Narita, Chiba, Japan, 286-8523

Novartis Investigative Site; Recruiting

Osaka-city, Osaka, Japan, 540-0006

Korea, Republic of

Novartis Investigative Site; Recruiting

Jeollanam, Korea, Republic of, 519763

Novartis Investigative Site; Recruiting

Seoul, Korea, Republic of, 06351

Malaysia

Novartis Investigative Site; Recruiting

Kota Kinabalu, Sabah, Malaysia, 88586

Novartis Investigative Site; Recruiting

Kuching, Sarawak, Malaysia, 93586

Novartis Investigative Site; Recruiting

Johor Bahru, Malaysia, 80100

Novartis Investigative Site; Recruiting

Pulau Pinang, Malaysia, 10990

Novartis Investigative Site; Recruiting

Selangor, Malaysia, 68000

Netherlands

Novartis Investigative Site; Recruiting

Utrecht, Netherlands, 3584 CX

Norway

Novartis Investigative Site; Recruiting

Gralum, Norway, 1714

Singapore

Novartis Investigative Site; Recruiting

Singapore, Singapore, 119228

Novartis Investigative Site; Recruiting

Singapore, Singapore, 169608

Novartis Investigative Site; Recruiting

Singapore, Singapore, S308433

Spain

Novartis Investigative Site; Recruiting

Barcelona, Catalunya, Spain, 08003

Novartis Investigative Site; Recruiting

Madrid, Spain, 28046

Turkey

Novartis Investigative Site; Recruiting

Aydin, Turkey, 09100

Novartis Investigative Site; Recruiting

Samsun, Turkey, 55139

United Kingdom

Novartis Investigative Site; Recruiting

Truro, Cornwall, United Kingdom, TR1 3LJ

Novartis Investigative Site; Recruiting

London, United Kingdom, W12 0HS

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

More Information

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT05653219
• Other Study ID Numbers: CVAY736Q12301
• First Posted: December 16, 2022
• Last Update Posted: May 26, 2023
• Last Verified: May 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

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

• URL: https://www.clinicalstudydatarequest.com

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

Primary immune thrombocytopenia (ITP),; ianalumab; VAY736; B-cell depletion; B-cell Activating Factor Receptor (BAFF-R) blockade; eltrombopag

Additional relevant MeSH terms:

Thrombocytopenia; Immune System Diseases; Purpura, Thrombocytopenic, Idiopathic; Blood Platelet Disorders; Hematologic Diseases; Purpura, Thrombocytopenic; Purpura; Blood Coagulation Disorders; Thrombotic Microangiopathies; Hemorrhagic Disorders; Autoimmune Diseases; Hemorrhage; Pathologic Processes; Skin Manifestations