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

Primary Immune Thrombocytopenia (ITP) Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05885555
• Other study ID #: CVAY736Q12201
• Secondary ID: 2022-503041-21
• Status: Recruiting
• Phase: Phase 2
• Start date: August 16, 2023
• Est. completion date: March 19, 2029

Study information

• Verified date: May 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 therapeutic efficacy, safety and tolerability of ianalumab in adult patients with primary ITP previously treated with at least one corticosteroid and one TPO-RA.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: March 19, 2029
• Est. primary completion date: March 15, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Biological:
• Ianalumab
Intravenous infusion, prepared from concentrate solution

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Australia	Novartis Investigative Site	Canberra	Australian Capital Territory
Australia	Novartis Investigative Site	Prahran	Victoria
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Jinan
China	Novartis Investigative Site	Wuhan	Hubei
Czechia	Novartis Investigative Site	Brno Bohunice	Czech Republic
France	Novartis Investigative Site	Dijon
France	Novartis Investigative Site	Toulouse
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Giessen
Germany	Novartis Investigative Site	Jena
Italy	Novartis Investigative Site	Firenze	FI
Italy	Novartis Investigative Site	Torino	TO
Italy	Novartis Investigative Site	Trieste	TS
Korea, Republic of	Novartis Investigative Site	Seoul	Seocho Gu
Korea, Republic of	Novartis Investigative Site	Seoul
Malaysia	Novartis Investigative Site	Johor Bahru
Malaysia	Novartis Investigative Site	Kota Kinabalu	Sabah
Malaysia	Novartis Investigative Site	Kuching	Sarawak
Poland	Novartis Investigative Site	Katowice
Poland	Novartis Investigative Site	Krakow
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Cordoba	Andalucia
Spain	Novartis Investigative Site	Madrid
Turkey	Novartis Investigative Site	Aydin
Turkey	Novartis Investigative Site	Edirne
Turkey	Novartis Investigative Site	Istanbul	TUR
Turkey	Novartis Investigative Site	Izmir
Turkey	Novartis Investigative Site	Kocaeli
United Kingdom	Novartis Investigative Site	Glasgow
United Kingdom	Novartis Investigative Site	London
United States	New York Oncology Hematology Saratoga NYOH	Albany	New York
United States	Beth Israel Deaconess Medical Cente	Boston	Massachusetts
United States	Massachusetts General Hospital .	Boston	Massachusetts
United States	Virginia Oncology Associates .	Norfolk	Virginia
United States	University of Pennsylvania IDS Central	Philadelphia	Pennsylvania
United States	Georgetown University Lombardi Cancer Center Dept. of Pharmacy Research 4	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  China,  Czechia,  France,  Germany,  Italy,  Korea, Republic of,  Malaysia,  Poland,  Spain,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
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 to assess the immunogenicity of ianalumab	Up to 20 weeks after last dose of ianalumab
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 to assess the immunogenicity of ianalumab	Up to 20 weeks after last dose of ianalumab
Secondary	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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