Primary Immune Thrombocytopenia (ITP)
Conditions
Keywords
Primary immune thrombocytopenia (ITP), ianalumab, VAY736, B-cell depletion, B-cell Activating Factor Receptor (BAFF-R) blockade
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 increasing the rate of stable response off treatment at 12 months (SROT-12) in adult participants with primary ITP.
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. The efficacy and safety follow-up period will last until treatment failure or up to 39 months after randomization of the last patient, whichever occurs first. Safety follow-up period will be performed for at least 20 weeks and up to 2 years after the last ianalumab/placebo dose. The primary endpoint was updated in May 2026 to stable response off treatment at 12 months (SROT-12). The previous primary endpoint, time to treatment failure (TTF), remains in the study as a key secondary objective.
Interventions
BIOLOGICALIanalumab
Intravenous infusion, prepared from concentrate solution
DRUGPlacebo
Intravenous infusion, prepared from matching placebo
DRUGCorticosteroids
Oral or parental (if clinically justified)
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
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 (patients with low grade anemia related to bleeding or iron deficiency are eligible) * Current life-threatening bleeding * Previous ITP treatment, including splenectomy, except for corticosteroids and/or IVIG initiated as first-line therapy for up to 28 days before randomization and rescue corticosteroids and/or IVIG given prior to confirmed diagnosis of primary ITP . * 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 Other protocol-defined Inclusion/Exclusion may apply.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Stable Response off treatment at 12 months (SROT-12) | 12 months after last patient completed treatment | A participant will be considered in SROT-12 if at least 75% of the platelet counts collected between visits Week 53 Day 1 and Week 65 Day 1 (Study Days 352 and 463) qualify as Response. Response is any platelet counts of at least 50 G/L in the absence of rescue treatment or new immune thrombocytopenia (ITP) treatment). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time from randomization to Treatment Failure (TTF) (Key Secondary Endpoint) | Randomization to end of study (up to 39 months after randomization of last patient | Time to Treatment Failure (TTF) is defined as the time from randomization until the first of the following events/situation indicative of treatment failure: platelet count below 30 G/L later than 8 weeks from randomization, need for a rescue treatment later than 8 weeks from randomization, intake of rescue treatment (e.g., corticosteroids, Intravenous immunoglobulins (IVIG), or platelet transfusion) given later than 8 weeks from randomization, start of new Immune Thrombocytopenia (ITP) treatment whenever it occurs, death (whatever the cause). |
| 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 |
| Stable response at 6 months | At 6 months | Percentage of participants with at least 2 platelet count collected at month 6 (between study dates 107 and 183) and at least 66% of platelet counts qualified as a response |
| Stable response at 1 year | At 1 year | Percentage of participants with at least 2 platelet counts collected at year 1 (between study days 296 and 379) and at least 66% of platelet counts qualified as a 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 T 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 is defined as ≥80% of baseline and ≥LLOQ, 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 |
Countries
Argentina, Australia, Austria, Belgium, Bulgaria, China, Czechia, France, Germany, Hong Kong, Hungary, India, Italy, Japan, Malaysia, Mexico, Norway, Romania, Singapore, Spain, Thailand, Turkey (Türkiye), United Kingdom, United States, Vietnam
Contacts
STUDY_DIRECTORNovartis Pharmaceuticals
Novartis Pharmaceuticals
Outcome results
None listed