A Study of Ianalumab (VAY736) in Patients With Primary Immune Thrombocytopenia (ITP) Previously Treated With at Least Two Lines of Therapies

A Phase 2 Study to Evaluate the Efficacy and Safety of Ianalumab (VAY736) in Patients With Primary Immune Thrombocytopenia (ITP) Previously Treated With at Least a Corticosteroid and a Thrombopoietin Receptor Agonist (TPO-RA)

The purpose of this study is to evaluate the therapeutic efficacy, safety and tolerability of ianalumab in adult patients with primary ITP previously treated with at least one corticosteroid and one TPO-RA.

Study Overview

• Status: Recruiting
• Conditions: Primary Immune Thrombocytopenia (ITP)
• Intervention / Treatment: Biological: Ianalumab

Detailed Description

This is a phase 2, open-label, single-arm study to evaluate the efficacy, safety and tolerability of ianalumab in participants with primary ITP (platelet count <30 G/L at screening) previously treated with at least a corticosteroid and a TPO-RA.

The study consists of the screening period, the primary endpoint assessment period, the follow-up period. The screening period will last for up to 14 days prior to the first dose of ianalumab. All eligible participants will be treated with the same dose of ianalumab and will complete the primary endpoint assessment period. After completion of the primary endpoint assessment period, all participants will continue in safety monitoring and those with a platelet count ≥30 G/L in absence of a new line of ITP therapy and rescue therapy will also continue in efficacy monitoring. The trial includes an option to offer a second course of ianalumab treatment to participants who achieved confirmed response during the initial course of ianalumab and later lost response to explore the benefit of the second course of treatment. The study will end once all participants have completed 24 months of safety follow-up since their last dose of ianalumab (including the optional second course of ianalumab treatment),or discontinued the study earlier.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Novartis Pharmaceuticals; Phone Number: 1-888-669-6682; Email: novartis.email@novartis.com
• Study Contact Backup: Name: Novartis Pharmaceuticals; Phone Number: +41613241111

Study Locations

• Argentina
  • Buenos Aires
    • Caba, Buenos Aires, Argentina, C1181ACH
      • Recruiting
      • Novartis Investigative Site
• Australia
  • Australian Capital Territory
    • Canberra, Australian Capital Territory, Australia, 2605
      • Recruiting
      • Novartis Investigative Site
  • Victoria
    • Prahran, Victoria, Australia, 3181
      • Recruiting
      • Novartis Investigative Site
• China
  • Beijing, China, 100730
    • Recruiting
    • Novartis Investigative Site
  • Jinan, China, 250012
    • Recruiting
    • Novartis Investigative Site
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Active, not recruiting
      • Novartis Investigative Site
• Czechia
  • Czech Republic
    • Brno Bohunice, Czech Republic, Czechia, 625 00
      • Recruiting
      • Novartis Investigative Site
• France
  • Dijon, France, 21034
    • Recruiting
    • Novartis Investigative Site
  • Toulouse, France, 31059
    • Recruiting
    • Novartis Investigative Site
• Germany
  • Dresden, Germany, 01307
    • Recruiting
    • Novartis Investigative Site
  • Giessen, Germany, 35392
    • Recruiting
    • Novartis Investigative Site
  • Jena, Germany, 07740
    • Recruiting
    • Novartis Investigative Site
• Italy
  • FI
    • Firenze, FI, Italy, 50134
      • Recruiting
      • Novartis Investigative Site
  • TO
    • Torino, TO, Italy, 10126
      • Recruiting
      • Novartis Investigative Site
  • TS
    • Trieste, TS, Italy, 34129
      • Recruiting
      • Novartis Investigative Site
• Korea, Republic of
  • Seoul, Korea, Republic of, 06351
    • Recruiting
    • Novartis Investigative Site
  • Seocho Gu
    • Seoul, Seocho Gu, Korea, Republic of, 06591
      • Recruiting
      • Novartis Investigative Site
• Malaysia
  • Johor Bahru, Malaysia, 80100
    • Recruiting
    • Novartis Investigative Site
  • Sabah
    • Kota Kinabalu, Sabah, Malaysia, 88586
      • Recruiting
      • Novartis Investigative Site
  • Sarawak
    • Kuching, Sarawak, Malaysia, 93586
      • Recruiting
      • Novartis Investigative Site
• Poland
  • Katowice, Poland, 40-519
    • Recruiting
    • Novartis Investigative Site
  • Krakow, Poland, 30-688
    • Recruiting
    • Novartis Investigative Site
• Spain
  • Madrid, Spain, 28009
    • Recruiting
    • Novartis Investigative Site
  • Andalucia
    • Cordoba, Andalucia, Spain, 14004
      • Recruiting
      • Novartis Investigative Site
  • Catalunya
    • Barcelona, Catalunya, Spain, 08003
      • Recruiting
      • Novartis Investigative Site
• Turkey
  • Aydin, Turkey, 09100
    • Recruiting
    • Novartis Investigative Site
  • Edirne, Turkey, 22030
    • Recruiting
    • Novartis Investigative Site
  • Izmir, Turkey, 35040
    • Recruiting
    • Novartis Investigative Site
  • Kocaeli, Turkey, 41380
    • Recruiting
    • Novartis Investigative Site
  • TUR
    • Istanbul, TUR, Turkey, 34098
      • Recruiting
      • Novartis Investigative Site
• United Kingdom
  • Glasgow, United Kingdom, G31 2ER
    • Recruiting
    • Novartis Investigative Site
  • London, United Kingdom, W12 0HS
    • Recruiting
    • Novartis Investigative Site
• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20007 2197
      • Recruiting
      • Georgetown University Lombardi Cancer Center Dept. of Pharmacy Research (4)
      • Principal Investigator: Catherine Broome
      • Contact: Stefan Jenss; Phone Number: 202-444-3771; Email: Sej49@georgetown.edu
  • New York
    • Albany, New York, United States, 12208
      • Recruiting
      • New York Oncology Hematology Saratoga NYOH
      • Contact: Edward Hagopian; Email: edward.hagopian@usoncology.com
      • Principal Investigator: Mihir Pradipkumar Raval
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • University of Pennsylvania IDS Central
      • Contact: Mary Kelty; Email: Mary.Kelty@pennmedicine.upenn.edu
      • Principal Investigator: Adam Cuker

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Signed informed consent obtained prior to participation in the study.
• Male or female participants aged 18 years and older on the day of signing informed consent.

• Confirmed diagnosis of primary ITP.

  • Prior treatment with at least a corticosteroid (±IVIG) and a TPO-RA:
  • Prior additional therapies are allowed; the corticosteroid or the TPO-RA do not need to be the last treatment.
  • Prior response to IVIG/anti-D or a corticosteroid (platelet count ≥50 G/L) that was not maintained.
• At last ITP treatment, loss of response, insufficient response, no response or intolerance.
• Platelet count <30 G/L and assessed as needing treatment (per physician's discretion) at screening. If concomitant ITP medication is clinically indicated, the platelet assessment showing a value <30 G/L must be performed after at least 14 days on a stable dose of a corticosteroid or/and a TPO-RA (less than 10% variation from current dose) and continue stable thereafter.

Key exclusion criteria:

• Diagnosis of secondary thrombocytopenia.
• Platelet or whole blood transfusion, plasmapheresis, or use of any other rescue medications within 14 days before first ianalumab infusion.

• Participants with the following conditions at screening:

  • Neutrophils <1000/mm3.
  • Immunoglobulin G (IgG) <5 g/L
• Treatment with a B-cell depleting therapy (e.g., rituximab) or anti-B-cell Activating Factor of the TNF Family (BAFF) (e.g., belimumab) within 12 weeks prior to the first administration of ianalumab.
• Immunosuppressant drugs other than corticosteroids within 5 times the elimination half-life of the drug or 14 days before first ianalumab infusion, whichever is longer.
• Prior splenectomy.

Other protocol-defined inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single-arm; All eligible participants will receive ianalumab at the same dose.	Biological: Ianalumab; Intravenous infusion, prepared from concentrate solution; Other Names: VAY736

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Confirmed response	Confirmed response is defined as a platelet count of equal or above 50 G/L at two (or more) consecutive assessments at least 7 days apart, in the absence of: Rescue treatment for ≥4 weeks prior to the assessment of the platelet count, and; New immune thrombocytopenia (ITP) treatment before reaching a confirmed response.	Between Week 1 Day 1 and Week 25 Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to confirmed response	Time from the first administration of ianalumab to the first assessment in the first sequence of two (or more) platelet assessments meeting the criteria of a confirmed response as defined by the primary endpoint.	From Week 1 Day 1 to Week 25 Day 1
Duration of confirmed response	Time from the first assessment in the first sequence of two (or more) platelet assessments meeting the criteria of a confirmed response to loss of response; with loss of response defined as the first of the following events: platelet count <30 G/L,; start of any rescue or new ITP treatment,; death (whatever the cause).	From Week 1 Day 1 to end of study (until all participants have completed 24 months of safety follow-up since their last dose of ianalumab or discontinued the study earlier)
Complete Response rate at each timepoint	Percentage of participants with a platelet count of at least 100 G/L in the absence of rescue treatment/new ITP treatment.	From Week 1 Day 1 to end of study (until all participants have completed 24 months of safety follow-up since their last dose of ianalumab or discontinued the study earlier)
Response rate at each timepoint	Percentage of participants with a platelet count of at least 50 G/L in the absence of rescue treatment/new ITP treatment.	From Week 1 Day 1 to end of study (until all participants have completed 24 months of safety follow-up since their last dose of ianalumab or discontinued the study earlier)
Stable response at 6 months	Percentage of participants with at least 75% of platelet counts collected at month 6 (between study days 121 and 183) equal to or above 50 G/L in the absence of rescue treatment/new ITP treatment.	At 6 months
Stable response at 1 year	Percentage of participants with at least 66% of platelet counts collected at year 1 (between study days 296 and 379) equal to or above 50 G/L in the absence of rescue treatment/new ITP treatment.	At 1 year
Percentage of participants with bleeding events according to the Modified World Health Organization (WHO) bleeding scale	Percentage of participants reporting bleeding events for each grade of the WHO bleeding scale at each time point. Severity is graded from 0 to 4, with 0 = no bleeding and 4 = severe hemodynamic instability/central nervous system (CNS) bleeding/fatal.	From Week 1 Day 1 to end of study (until all participants have completed 24 months of safety follow-up since their last dose of ianalumab or discontinued the study earlier)
Number of participants who received rescue treatment	Number of participants who required rescue treatment	From Week 1 Day 1 to end of study (until all participants have completed 24 months of safety follow-up since their last dose of ianalumab or discontinued the study earlier)
Percentage of participants who received rescue treatment	Percentage of participants who required rescue treatment	From Week 1 Day 1 to end of study (until all participants have completed 24 months of safety follow-up since their last dose of ianalumab or discontinued the study earlier)
Change from baseline in the frequency of CD19+ B-cell counts	Post-baseline frequency of CD19+ B-cell counts compared to baseline	From Week 1 Day 1 to end of study (until all participants have completed 24 months of safety follow-up since their last dose of ianalumab or discontinued the study earlier)
Change from baseline in the absolute number of CD19+ B-cell counts	Post-baseline absolute number of CD19+ B-cell counts compared to baseline	From Week 1 Day 1 to end of study (until all participants have completed 24 months of safety follow-up since their last dose of ianalumab or discontinued the study earlier)
Time to first occurrence 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	From Week 1 Day 1 to end of study (until all participants have completed 24 months of safety follow-up since their last dose of ianalumab or discontinued the study earlier)
Change from baseline in immunoglobulins	Post-baseline immunoglobulin levels (change in titers of Total Ig, IgG, IgM, IgA) compared to baseline	From Week 1 Day 1 to end of study (until all participants have completed 24 months of safety follow-up since their last dose of ianalumab or discontinued the study earlier)
Incidence of anti-ianalumab antibodies in serum (ADA assay) over time	Anti-drug antibodies (ADA) will be evaluated in samples collected from all participants to assess the immunogenicity of ianalumab	Up to 20 weeks after last dose of ianalumab
Titer of anti-ianalumab antibodies in serum (ADA assay) over time	Anti-drug antibodies (ADA) will be evaluated in samples collected from all participants to assess the immunogenicity of ianalumab	Up to 20 weeks after last dose of ianalumab
Ianalumab serum concentrations over time	Ianalumab concentration in serum over time, including end of infusion and concentration at trough.	First dose (pre-dose, 2, 168, 336, 504, 672 hours post-dose); Subsequent doses (pre-dose and 2 hours post-dose); Last dose (pre-dose, 2 336, 672, 1344, 2016, 3360 hours post-dose)
Bleeding events according to the Modified World Health Organization (WHO) bleeding scale	Number of participants reporting bleeding events for each grade of the World Health Organization (WHO) bleeding scale at each time point. Severity is graded from 0 to 4, with 0 = no bleeding and 4 = severe hemodynamic instability/central nervous system (CNS) bleeding/fatal.	From Week 1 Day 1 to end of study (until all participants have completed 24 months of safety follow-up since their last dose of ianalumab or discontinued the study earlier)
Confirmed response (CR) in the second course	Confirmed response is defined as a platelet count of equal or above 50 G/L at two (or more) consecutive assessments at least 7 days apart, in the absence of: Rescue treatment for ≥4 weeks prior to the assessment of the platelet count, and; New ITP treatment before reaching a confirmed response.	Second course Week 1 Day1 to second course Week 25 Day1
Time to confirmed response in the second course	two (or more) platelet assessments meeting the criteria of a confirmed response.	Second course Week 1 Day 1 to second course Week 25 Day 1
Duration of confirmed response in the second course	Time from the first assessment, in the second course of two (or more) platelet assessments meeting the criteria of a confirmed response to loss of response; with loss of response defined as the first of the following events: platelet count <30 G/L,; start of any rescue or new ITP treatment,; death (whatever the cause).	Second course Week 1 Day 1 to second course Week 25 Day 1
Response in the second course	Percentage of participants with a platelet count of at least 50 G/L in the absence of rescue treatment/new ITP treatment.	Second course Week 1 Day 1 to second course Week 25 Day 1
Complete Response in the second course	Percentage of participants with a platelet count of at least 100 G/L in the absence of rescue treatment/new ITP treatment.	Second course Week 1 Day 1 to second course Week 25 Day 1
Bleeding events in the second course according to the Modified World Health Organization (WHO) bleeding scale	Number of participants reporting bleeding events for each grade of the World Health Organization (WHO) bleeding scale at each time point. Severity is graded from 0 to 4, with 0 = no bleeding and 4 = severe hemodynamic instability/central nervous system (CNS) bleeding/fatal.	Second course Week 1 Day 1 to second course Week 25 Day 1
Percentage of participants with bleeding events in the retreatment/second courseaccording to the Modified World Health Organization (WHO) bleeding scale	Percentage of participants reporting bleeding events for each grade of the WHO bleeding scale at each time point. Severity is graded from 0 to 4, with 0 = no bleeding and 4 = severe hemodynamic instability/central nervous system (CNS) bleeding/fatal.	Second course Week 1 Day 1 to second course Week 25 Day 1
Percentage of participants who received rescue treatment after receiving second course	Percentage of participants who required rescue treatment	Second course Week 1 Day 1 to second course Week 25 Day 1
Titer of anti-ianalumab antibodies in serum (ADA assay) over time for second course	Anti-drug antibodies (ADA) will be evaluated in samples collected from all participants to assess the immunogenicity of ianalumab	Second course Week 1 Day 1 until 20 weeks after last dose of ianalumab
Change from start of second course in immunoglobulins	Post-baseline immunoglobulin levels (change in titers of Total Ig, IgG, IgM, IgA) compared to retreatment baseline	From second course Week 1 Day 1 to end of study (until all participants have completed 24 months of safety follow-up since their last dose of ianalumab or discontinued the study earlier)
Change from start of second course in the absolute number of CD19+ B-cell counts	Post-baseline absolute number of CD19+ B-cell counts compared to baseline	From second course Week 1 Day 1 to end of study (until all participants have completed 24 months of safety follow-up since their last dose of ianalumab or discontinued the study earlier)
Change from start of second course to end of study in the absolute number of CD19+ B-cell counts	Post-baseline absolute number of CD19+ B-cell counts compared to baseline	From second course Week 1 Day 1 to end of study (until all participants have completed 24 months of safety follow-up since their last dose of ianalumab or discontinued the study earlier)
Time to first occurrence 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	From second course Week 1 Day 1 to end of study (until all participants have completed 24 months of safety follow-up since their last dose of ianalumab or discontinued the study earlier)
Ianalumab serum concentrations over time in the second course	Ianalumab concentration in serum over time, including end of infusion and concentration at trough.	First dose (pre-dose, 2, 168, 336, 504, 672 hours post-dose); Subsequent doses (pre-dose and 2 hours post-dose); Last dose (pre-dose, 2 336, 672, 1344, 2016, 3360 hours post-dose) in the second course
Number of Participants who received rescue treatment after second course	Number of participants who required rescue treatment	Second course Week 1 Day 1 to second course Week 25 Day 1

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): August 16, 2023
• Primary Completion (Estimated): March 15, 2027
• Study Completion (Estimated): March 19, 2029

Study Registration Dates

• First Submitted: May 15, 2023
• First Submitted That Met QC Criteria: May 30, 2023
• First Posted (Actual): June 2, 2023

Study Record Updates

• Last Update Posted (Actual): March 26, 2024
• Last Update Submitted That Met QC Criteria: March 25, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: VAY736; B-cell depletion; ianalumab; B-cell Activating Factor Receptor (BAFF-R) blockade; Primary immune thrombocytopenia (ITP)
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Autoimmune Diseases; Hematologic Diseases; Hemorrhage; Hemorrhagic Disorders; Blood Coagulation Disorders; Skin Manifestations; Blood Platelet Disorders; Thrombotic Microangiopathies; Purpura, Thrombocytopenic; Purpura; Cytopenia; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia
• Other Study ID Numbers: CVAY736Q12201; 2022-503041-21 (Registry 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