Clinical trial NCT05885555: A Study of Ianalumab (VAY736) in Patients With Primary Immune Thrombocytopenia (ITP) Previously Treated With at Least Two Lines of Therapies
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Primary Immune Thrombocytopenia (ITP)
Keywords: Primary immune thrombocytopenia (ITP)
ianalumab
VAY736
B-cell depletion
B-cell Activating Factor Receptor (BAFF-R) blockade
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2023-06-02
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Confirmed response
timeFrame: Between Week 1 Day 1 and Week 25 Day 1
Secondary outcomes:
measure: Time to confirmed response
timeFrame: From Week 1 Day 1 to Week 25 Day 1
measure: Duration of confirmed response
timeFrame: 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)
measure: Complete Response rate at each timepoint
timeFrame: 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)
measure: Response rate at each timepoint
timeFrame: 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)
measure: Stable response at 6 months
timeFrame: At 6 months
measure: Stable response at 1 year
timeFrame: At 1 year
measure: Bleeding events according to the Modified World Health Organization (WHO) bleeding scale
timeFrame: 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)
measure: Percentage of participants with bleeding events according to the Modified World Health Organization (WHO) bleeding scale
timeFrame: 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)
measure: Number of participants who received rescue treatment
timeFrame: 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)
measure: Percentage of participants who received rescue treatment
timeFrame: 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)
measure: Change from baseline in the frequency of CD19+ B-cell counts
timeFrame: 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)
measure: Change from baseline in the absolute number of CD19+ B-cell counts
timeFrame: 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)
measure: Time to first occurrence of B-cell recovery defined as ≥80% of baseline ≥50 cells/µL
timeFrame: 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)
measure: Change from baseline in immunoglobulins
timeFrame: 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)
measure: Incidence of anti-ianalumab antibodies in serum (ADA assay) over time
timeFrame: Up to 20 weeks after last dose of ianalumab
measure: Titer of anti-ianalumab antibodies in serum (ADA assay) over time
timeFrame: Up to 20 weeks after last dose of ianalumab
measure: Ianalumab serum concentrations over time
timeFrame: 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)
measure: Ianalumab serum PK: AUC concentrations over time
timeFrame: 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)
measure: Ianalumab serum PK parameters: Cmax
timeFrame: 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)
measure: Ianalumab serum PK parameters: Tmax
timeFrame: 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)
measure: Confirmed response (CR) in the second course
timeFrame: Second course Week 1 Day1 to second course Week 25 Day1
measure: Time to confirmed response in the second course
timeFrame: Second course Week 1 Day 1 to second course Week 25 Day 1
measure: Duration of confirmed response in the second course
timeFrame: Second course Week 1 Day 1 to second course Week 25 Day 1
measure: Response in the second course
timeFrame: Second course Week 1 Day 1 to second course Week 25 Day 1
measure: Complete Response in the second course
timeFrame: Second course Week 1 Day 1 to second course Week 25 Day 1
measure: Bleeding events in the second course according to the Modified World Health Organization (WHO) bleeding scale
timeFrame: Second course Week 1 Day 1 to second course Week 25 Day 1
measure: Percentage of participants with bleeding events in the retreatment/second courseaccording to the Modified World Health Organization (WHO) bleeding scale
timeFrame: Second course Week 1 Day 1 to second course Week 25 Day 1
measure: Number of Participants who received rescue treatment after second course
timeFrame: Second course Week 1 Day 1 to second course Week 25 Day 1
measure: Percentage of participants who received rescue treatment after receiving second course
timeFrame: Second course Week 1 Day 1 to second course Week 25 Day 1
measure: Titer of anti-ianalumab antibodies in serum (ADA assay) over time for second course
timeFrame: Second course Week 1 Day 1 until 20 weeks after last dose of ianalumab
measure: Change from start of second course in immunoglobulins
timeFrame: 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)
measure: Change from start of second course in the absolute number of CD19+ B-cell counts
timeFrame: 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)
measure: Change from start of second course to end of study in the absolute number of CD19+ B-cell counts
timeFrame: 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)
measure: Time to first occurrence of B-cell recovery defined as ≥80% of baseline ≥50 cells/µL
timeFrame: 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)
measure: Ianalumab serum concentrations over time in the second course
timeFrame: 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
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Cente
state: Massachusetts
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Canberra
country: Australia
facility: Novartis Investigative Site
state: Australian Capital Territory
city: Melbourne
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Wuhan
country: China
facility: Novartis Investigative Site
state: Hubei
city: Beijing
country: China
facility: Novartis Investigative Site
city: Jinan
country: China
facility: Novartis Investigative Site
city: Toulouse
country: France
facility: Novartis Investigative Site
city: Dresden
country: Germany
facility: Novartis Investigative Site
city: Giessen
country: Germany
facility: Novartis Investigative Site
city: Jena
country: Germany
facility: Novartis Investigative Site
city: Torino
country: Italy
facility: Novartis Investigative Site
state: TO
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Seocho Gu
city: Johor Bahru
country: Malaysia
facility: Novartis Investigative Site
city: Katowice
country: Poland
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
state: TUR
city: Aydin
country: Turkey
facility: Novartis Investigative Site
city: Edirne
country: Turkey
facility: Novartis Investigative Site
city: Izmir
country: Turkey
facility: Novartis Investigative Site
city: Kocaeli
country: Turkey
facility: Novartis Investigative Site
city: Glasgow
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: