A Study of Efficacy and Safety of Ianalumab Versus Placebo in Addition to Eltrombopag in Primary Immune Thrombocytopenia Patients Who Failed Steroids

Phase 3Active Not RecruitingNCT05653219

Novartis Pharmaceuticals152 enrolled

Overview

The purpose of this study is to evaluate the effect of two different doses of ianalumab added to eltrombopag to prolong Time to Treatment Failure (TTF) in adults with primary ITP who failed previous first-line treatment with steroids.

This is a multicenter, randomized, double-blinded phase 3 study to assess efficacy and safety of two different doses of ianalumab versus placebo in addition to eltrombopag in adults with primary ITP (platelet count \<30 G/L) who failed previous first-line treatment with corticosteroids. After completion of the screening period, the participants will enter the randomized treatment period (ianalumab/placebo with eltrombopag) followed by the eltrombopag tapering period. Afterwards, all participants will enter the follow-up period to be monitored for efficacy and safety or safety only depending on how the participants responded to the study treatment.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

152

Conditions

Primary Immune Thrombocytopenia

Interventions

IanalumabBIOLOGICAL

Concentrate for solution for infusion for intravenous use

EltrombopagDRUG

Film-coated tablet for oral use

PlaceboDRUG

Concentrate for solution for infusion for intravenous use.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 100 Years

Medical Language ↔ Plain English

Key Inclusion criteria 1. Male or female patients aged 18 years and older on the day of signing the informed consent. 2. A signed informed consent must be obtained prior to participation in the study. 3. A diagnosis of primary ITP, with insufficient response to, or relapse after a first-line corticosteroid therapy ± IVIG. 4. Patient with platelet count \<30G/L (whom eltrombopag is clinically indicated as per physician's discretion) and with no contraindication to receive eltrombopag Key Exclusion criteria 1. ITP patients who received second-line ITP treatments (other than steroid therapy± IVIG) including splenectomy. However, patients exposed to thrombopoietin receptor agonists (TPO-RAs) for a limited time (max one week) before screening are eligible. 2. Patients with key lab abnormalities and patients with Evans syndrome or any other cytopenia, (patients with low grade anemia related to bleeding or iron deficiency are eligible). 3. Patients with history of clinically significant hematological disorders, or with marked altered hematologic parameters 4. Patients with current or history of life-threatening bleeding 5. Patient that are Human Immunodeficiency Virus (HIV), Hepatitis C Virus (HCV), Hepatitis B surface Antigen (HBsAg)/ Hepatitis B core antibody (HBcAb)-positive. HBcAb-positive patients can be enrolled if HBsAg negative, HBV DNA negative, no pre-existing liver fibrosis is present and antiviral prophylaxis is given 6. Patients with known active or uncontrolled infection requiring systemic treatment during screening period 7. Patients with hepatic impairment 8. Patients with concurrent coagulation disorders and/or receiving antiplatelet or anticoagulant medication with an exemption of low dose of acetylsalicylic acid (≤150 mg daily) 9. Nursing (breast feeding) or pregnant women Other protocol-defined inclusion/exclusion criteria may apply.

Locations (74)

Outcomes

Primary Outcomes

Time from randomization until treatment failure

Time from randomization until treatment failure is defined as the time from randomization date until the first of the following events indicative of treatment failure: * platelet count below 30 G/L * start of a new ITP treatment * need for a rescue treatment * ineligibility to taper or inability to discontinue eltrombopag * death

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

Secondary Outcomes

Stable response at 6 months (Key Secondary Endpoint)

Percentage of participants with at least 3 platelet count collected at month 6 (between study days 121 and 183 and at least 75% of platelet counts qualified as a response).

Time frame: At 6 months

Complete Response rate at each timepoint

Percentage 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 until end of study (up to 39 months after randomization of last participant)

Response rate at each timepoint

Percentage 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 until end of study (up to 39 months after randomization of last participant)

Best response rate across all timepoints

Percentage of participants with a best response rate of either response or complete response

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

Time to first response/time to first complete response

Data from ClinicalTrials.gov

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Yuma Regional Medical Center

Yuma, Arizona, United States

University of Colorado Anschutz

Aurora, Colorado, United States

NorthShore University Health System

Evanston, Illinois, United States

Boston Medical Center

Boston, Massachusetts, United States

UMASS Memorial Medical Center

Worcester, Massachusetts, United States

Michigan Center of Medical Research

Farmington Hills, Michigan, United States

St Vincent Frontier Cancer Center

Billings, Montana, United States

Hematology Oncology Association of Rockland

Nyack, New York, United States

Montefiore Medical Center

The Bronx, New York, United States

Novartis Investigative Site

CABA, Argentina

...and 64 more locations

Time from randomization to date of first response and time from randomization to date of first complete response

Time frame: Time from randomization up to the longest observed treatment period duration

Duration of response

Time from achievement of response to treatment failure.

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

Stable response at 1 year

Percentage of participants with at least 2 platelet count 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

Duration of complete response

Time from achievement of complete response to loss of complete response stable response at 1 year period

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

Rate of participants who successfully taper and discontinue eltrombopag in each treatment arm

Probability to be treatment failure-free (as defined for the primary efficacy endpoint)

Time frame: up to week 24

Percentage of participants with bleeding events according to World Health Organization (WHO)

Percentage of participants reporting bleeding events according to WHO bleeding scale

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

Number of participants receiving rescue treatment

Number of participants who are in need of rescue treatment in each treatment arm

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

Percentage of participants receiving rescue treatment

Percentage of participants who are in need of rescue treatment

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

Change from baseline in the frequency of CD19+ B-cell counts

Post-baseline frequency of CD19+ B-cell counts (percentage within CD45) compared to baseline

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

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

Post-baseline absolute number of CD19+ B-cell counts compared to baseline

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

Change from baseline on T-score 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 in adults.

Time frame: From screening (baseline) until end of study (up 39 months after randomization of last participant)

Change from baseline in ITP PAQ domain scores of symptoms, fatigue, bother (uncomfortable), activity

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, overall QoL. Each item is rated on a Likert type scale. Each scale is scored from 0 to 100. Higher scores represent better HRQoL.

Time frame: From screening (baseline) until end of study (up 39 months after randomization of last participant)

Time to first occurence 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

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

Change from baseline in immunoglobulins

Change from baseline in immunoglobulin levels

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

PK parameters: AUClast

AUClast: Area under the curve from time zero to the last measurable concentration sampling time (tlast)

Time frame: After first dose (pre-dose, EOI, 168, 336 and 504 hours post dose) and after last dose (pre-dose, EOI, 336, 672, 2016, 3360 hours post dose)

PK parameters: AUCtau

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

Time frame: After first dose (pre-dose, EOI, 168, 336 and 504 hours post dose) and after last dose (pre-dose, EOI, 336, 672, 2016, 3360 hours post dose)

PK parameters: Cmax

Maximum (peak) observed plasma, blood, serum or other body fluid drug concentration

Time frame: After first dose (pre-dose, EOI, 168, 336 and 504 hours post dose) and after last dose (pre-dose, EOI, 336, 672, 2016, 3360 hours post dose)

PK parameters: Tmax

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

Time frame: After first dose (pre-dose, EOI, 168, 336 and 504 hours post dose) and after last dose (pre-dose, EOI, 336, 672, 2016, 3360 hours post dose)

PK parameters: Accumulation ratio Racc

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

Time frame: After last dose (pre-dose, EOI, 336, 672, 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 assessing 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 assessing the immunogenicity of ianalumab

Time frame: up to week 33