VAYHIT1: Study of Ianalumab Versus Placebo in Addition to First-line Corticosteroids in Primary Immune Thrombocytopenia (ITP)

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05653349

Collaborator

(none)

225

Enrollment

Location

Arms

62.4

Anticipated Duration (Months)

3.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the effect of two different doses of ianalumab versus placebo in addition to first-line corticosteroids in maintaining platelet count ≥30 G/L in adult participants with primary ITP.

Condition or Disease	Intervention/Treatment	Phase
Primary Immune Thrombocytopenia (ITP)	Biological: Ianalumab Drug: Placebo Drug: Corticosteroids	Phase 3

Detailed Description

This is a multi-center, randomized, double-blind Phase 3 study to assess the efficacy and safety of two different doses of ianalumab compared to placebo in adults with primary ITP (platelets count <30 G/L) who require first-line standard-of-care corticosteroids.

After completion of the screening period, the participants will enter the randomized treatment period (ianalumab/placebo with standard of care corticosteroids).

After the treatment period, all participants will enter the follow-up period to be monitored for efficacy and safety or safety only depending on how they respond to the study treatment.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

225 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Phase III, Randomized, Double-blind Study of Ianalumab (VAY736) Versus Placebo in Addition to First-line Corticosteroids in Primary Immune Thrombocytopenia (VAYHIT1)

Anticipated Study Start Date :

Jan 30, 2023

Anticipated Primary Completion Date :

Sep 25, 2025

Anticipated Study Completion Date :

Apr 13, 2028

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ianalumab Lower dose Lower dose of ianalumab administered intravenously with corticosteroids oral or parentally (if clinically justified)	Biological: Ianalumab Intravenously infusion, prepared from concentrate solution Other Names: VAY736 Drug: Corticosteroids Oral or parentally (if clinically justified)
Experimental: Ianalumab Higher dose Higher dose of ianalumab administered intravenously with corticosteroids oral or parentally (if clinically justified)	Biological: Ianalumab Intravenously infusion, prepared from concentrate solution Other Names: VAY736 Drug: Corticosteroids Oral or parentally (if clinically justified)
Placebo Comparator: Placebo Placebo administered intravenously with corticosteroids oral or parentally (if clinically justified)	Drug: Placebo Intravenously infusion, prepared from matching placebo Drug: Corticosteroids Oral or parentally (if clinically justified)

Arm

Intervention/Treatment

Experimental: Ianalumab Lower dose

Lower dose of ianalumab administered intravenously with corticosteroids oral or parentally (if clinically justified)

Biological: Ianalumab

Intravenously infusion, prepared from concentrate solution

Other Names:

VAY736

Drug: Corticosteroids

Oral or parentally (if clinically justified)

Experimental: Ianalumab Higher dose

Higher dose of ianalumab administered intravenously with corticosteroids oral or parentally (if clinically justified)

Biological: Ianalumab

Intravenously infusion, prepared from concentrate solution

Other Names:

VAY736

Drug: Corticosteroids

Oral or parentally (if clinically justified)

Placebo Comparator: Placebo

Placebo administered intravenously with corticosteroids oral or parentally (if clinically justified)

Drug: Placebo

Intravenously infusion, prepared from matching placebo

Drug: Corticosteroids

Oral or parentally (if clinically justified)

Outcome Measures

Primary Outcome Measures

Time from randomization to treatment failure (TTF) [Randomization to end of study (up to 39 months after randomization of last patient)]
Time from randomization until platelet count below 30 G/L, need for a rescue treatment or start of a second-line therapy or death.

Secondary Outcome Measures

Complete Response (CR) rate in each treatment group [Randomization to end of study (up to 39 months after randomization of last patient)]
Complete Response (CR) rate at each timepoint defined as the proportion of participants with any platelet count of at least 100 G/L in the absence of rescue treatment or new ITP treatment.
Response (R) rate in each treatment group [Randomization to end of study (up to 39 months after randomization of last patient)]
Response (R) rate at each timepoint defined as the proportion of participants with any platelet count of at least 50 G/L in the absence of rescue treatment or new ITP treatment.
Time to complete response in each treatment group [Randomization to end of study (up to 39 months after randomization of last patient)]
Time from randomization to date of first complete response.
Duration of response in each treatment group [Randomization to end of study (up to 39 months after randomization of last patient)]
Time from achievement of complete response to loss of complete response
Percentage of participants with bleeding events overall and by World Health Organization (WHO) bleeding scale severity [Randomization to end of study (up to 39 months after randomization of last patient)]
This is to assess the incidence and severity of bleeding in each treatment arm
Number of participants with bleeding events overall and by World Health Organization (WHO) bleeding scale severity [Randomization to end of study (up to 39 months after randomization of last patient)]
This is to assess the number and severity of bleeding in each treatment arm
Number of participants receiving rescue treatment (cummulative dose/duration of steroids exposure) [Randomization to end of study (up to 39 months after randomization of last patient)]
This is to assess the number of participants receiving rescue treatment.
Percentage of participants receiving rescue treatment (cummulative dose/duration of steroids exposure) [Randomization to end of study (up to 39 months after randomization of last patient)]
This is to assess the need of rescue treatment in each treatment group by percentage.
Cumulative dose/duration of steroids exposure [From screening to end of study (up to 39 months after randomization of last patient)]
Duration of exposure to corticosteroids calculated from randomization (first dose) to end of study or last last contact date (if the participant is lost to follow-up).
Change from baseline on total scores of the PROMIS SF v1.0 Fatigue 13a [From screening (baseline) till end of study (up to 39 months after randomization of last patient)]
The Patient-Reported Outcomes Measurement Information System (PROMIS) Short Form v1.0 Fatigue 13a includes 13 items that assess fatigue
Change from baseline in ITP-PAQ domain scores [From screening (baseline) till end of study (up to 39 months after randomization of last patient)]
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, and Overall QoL. Each item is rated on a Likert type scale
Change from baseline in frequency of CD19+ B cell counts [Randomization to end of study (up to 39 months after randomization of last patient)]
Post baseline frequency (%within the CD45) of CD19+ B cell counts compare to baseline.
Change from baseline in absolute number of CD19+ B cell counts [Randomization to end of study (up to 39 months after randomization of last patient)]
Post baseline absolute number of CD19+ B cell counts compare with baseline
Time to first occurrence of B-cell recovery [Randomization to end of study (up to 39 months after randomized of last patient)]
B-cell recovery, defined as ≥80% of baseline or ≥50 cells/μL
Change from baseline in inmmunoglobulins [Randomization to end of study (up to 39 months after last randomized patients)]
Change from baseline in immunoglobulin levels
PK parameters: AUClast [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 till the last measurable concentration sampling time (tlast)
PK parameter: AUCtau [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)]
Area under the curve calculated to the end of a dosing interval (tau)
PK parameters: Cmax [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 after single dose administration
PK parameters: Tmax [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) plasma, blood, serum, or other body fluid drug concentration
PK parameters: Accumulation ratio Racc [After last dose (pre-dose, 2, 336, 672, 1344, 2016, 3360 hours post dose)]
Accumulation ratio calculated using AUC values obtained between the last and first dose
Incidence of anti-ianalumab antibodies in serum (ADA assay) over time [Up to Week 33]
Anti-drug antibodies (ADA) will be evaluated in samples collected from all participants assess the immunogenicity of ianalumab
Titer of anti-ianalumab antibodies in serum (ADA assay) over time [Up to Week 33]
Anti-drug antibodies (ADA) will be evaluated in samples collected from all participants assess the immunogenicity of ianalumab

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Signed informed consent prior to participation in the study.
Male or female participants aged 18 years and older on the day of signing informed consent
Primary ITP diagnosed within 3 months before initiating first-line ITP therapy (corticosteroids, IVIG)
Platelet count below 30 G/L before starting any first-line ITP therapy (corticosteroids, IVIG)
Response (platelet count >=50 G/L) to corticosteroids (+/- IVIG) at any time prior to randomization. Note: Platelet count measured within 7 days of platelet transfusion will not be considered as response.

Key Exclusion Criteria:

Evans syndrome or any other cytopenia
Current life-threatening bleeding
Previous ITP treatment, including splenectomy, except for corticosteroids and/or IVIG for up to 28 days before randomization.
Prior use of B-cell depleting therapy (e.g., rituximab).
Absolute neutrophil count below 1.0 G/L at randomization
Participants with concurrent coagulation disorders and/or receiving anti-platelet or anticoagulant medication with an exemption of low dose of acetylsalicylic acid