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

Phase 3Active Not RecruitingNCT05653349

Novartis Pharmaceuticals226 enrolled

Overview

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.

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

226

Conditions

Primary Immune Thrombocytopenia (ITP)

Interventions

IanalumabBIOLOGICAL

Intravenous infusion, prepared from concentrate solution

PlaceboDRUG

Intravenous infusion, prepared from matching placebo

CorticosteroidsDRUG

Oral or parental (if clinically justified)

Eligibility

Sex: ALLMin age: 18 YearsMax age: 100 Years

Medical Language ↔ Plain English

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.

Locations (114)

Outcomes

Primary Outcomes

Time from randomization to treatment failure (TTF)

Time from randomization until platelet count below 30 G/L, need for a rescue treatment or start of a second-line therapy or death.

Time frame: Randomization to end of study (up to 39 months after randomization of last patient)

Secondary Outcomes

Complete Response (CR) rate in each treatment group

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.

Time frame: Randomization to end of study (up to 39 months after randomization of last patient)

Response (R) rate in each treatment group

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 frame: Randomization to end of study (up to 39 months after randomization of last patient)

Time to complete response in each treatment group

Time from randomization to date of first complete response.

Time frame: Randomization to end of study (up to 39 months after randomization of last patient)

Duration of response in each treatment group

Time from achievement of complete response to loss of complete response

Time frame: Randomization to end of study (up to 39 months after randomization of last patient)

Stable response 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

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Yuma Regional Medical Center

Yuma, Arizona, United States

Community Cancer Institute

Clovis, California, United States

Compassionate Care Res Group Inc

Fountain Valley, California, United States

University of Colorado Anschutz

Aurora, Colorado, United States

DH Cancer Research Center LLC

Margate, Florida, United States

Uni of Chi Medi Ctr Hema and Onco

Chicago, Illinois, United States

Parkview Research Center

Fort Wayne, Indiana, United States

Oncology Care Associates

Bethesda, Maryland, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Beth Israel Deaconess Med Center

Boston, Massachusetts, United States

...and 104 more locations

Time frame: At 6 months

Stable response 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

Time frame: At 1 year

Percentage of participants with bleeding events overall and by World Health Organization (WHO) bleeding scale severity

This is to assess the incidence and severity of bleeding in each treatment arm

Time frame: Randomization to end of study (up to 39 months after randomization of last patient)

Number of participants with bleeding events overall and by World Health Organization (WHO) bleeding scale severity

This is to assess the number and severity of bleeding in each treatment arm

Time frame: Randomization to end of study (up to 39 months after randomization of last patient)

Number of participants receiving rescue treatment (cummulative dose/duration of steroids exposure)

This is to assess the number of participants receiving rescue treatment.

Time frame: Randomization to end of study (up to 39 months after randomization of last patient)

Percentage of participants receiving rescue treatment (cummulative dose/duration of steroids exposure)

This is to assess the need of rescue treatment in each treatment group by percentage.

Time frame: Randomization to end of study (up to 39 months after randomization of last patient)

Cumulative dose/duration of steroids exposure

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).

Time frame: From screening to end of study (up to 39 months after randomization of last patient)

Change from baseline on T scores of the PROMIS SF v1.0 Fatigue 13a

The Patient-Reported Outcomes Measurement Information System (PROMIS) Short Form v1.0 Fatigue 13a includes 13 items that assess fatigue

Time frame: From screening (baseline) till end of study (up to 39 months after randomization of last patient)

Change from baseline in ITP-PAQ domain scores

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

Time frame: From screening (baseline) till end of study (up to 39 months after randomization of last patient)

Change from baseline in frequency of CD19+ B cell counts

Post baseline frequency (%within the CD45) of CD19+ B cell counts compare to baseline.

Time frame: Randomization to end of study (up to 39 months after randomization of last patient)

Change from baseline in absolute number of CD19+ B cell counts

Post baseline absolute number of CD19+ B cell counts compare with baseline

Time frame: Randomization to end of study (up to 39 months after randomization of last patient)

Time to first occurrence of B-cell recovery

B-cell recovery, defined as ≥80% of baseline or ≥50 cells/μL

Time frame: Randomization to end of study (up to 39 months after randomized of last patient)

Change from baseline in inmmunoglobulins

Change from baseline in immunoglobulin levels

Time frame: Randomization to end of study (up to 39 months after last randomized patients)

PK parameters: AUClast

AUClast: area under the curve from time zero till the last measurable concentration sampling time (tlast)

Time frame: 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)

PK parameter: AUCtau

Area under the curve calculated to the end of a dosing interval (tau)

Time frame: 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)

PK parameters: Cmax

Maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after single dose administration

Time frame: 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)

PK parameters: Tmax

Time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration

Time frame: 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)

PK parameters: Accumulation ratio Racc

Accumulation ratio calculated using AUC values obtained between the last and first dose

Time frame: After last dose (pre-dose, 2, 336, 672, 1344, 2016, 3360 hours post dose)

Incidence of anti-ianalumab antibodies in serum (ADA assay) over time

Anti-drug antibodies (ADA) will be evaluated in samples collected from all participants assess the immunogenicity of ianalumab

Time frame: Up to Week 33

Titer of anti-ianalumab antibodies in serum (ADA assay) over time

Anti-drug antibodies (ADA) will be evaluated in samples collected from all participants assess the immunogenicity of ianalumab

Time frame: Up to Week 33