A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate Efficacy and Safety of Mezagitamab Subcutaneous Injection in Participants with Chronic Primary Immune Thrombocytopenia

The primary objective of this trial is to assess the efficacy of mezagitamab compared with placebo in achieving durable platelet response in participants aged ≥18 years with chronic primary immune thrombocytopenia. Durable platelet response represents a clinically meaningful endpoint in chronic immune thrombocytopenia management, reflecting sustained improvement in platelet counts that may reduce bleeding risk and decrease the need for additional therapeutic interventions.

The secondary objectives include:

• To assess the efficacy of mezagitamab compared with placebo in achieving platelet response in participants aged ≥18 years with chronic immune thrombocytopenia.
• To assess the effects of mezagitamab compared with placebo on patient-reported symptoms of immune thrombocytopenia in participants aged ≥18 years with chronic immune thrombocytopenia.
• To assess the use of rescue therapy in participants aged ≥18 years receiving mezagitamab compared with those receiving placebo.
• To assess the effects of mezagitamab compared with placebo on occurrence of bleeding in participants aged ≥18 years with chronic immune thrombocytopenia.
• To determine the pharmacokinetic profile of mezagitamab in trial participants who are receiving mezagitamab.
• To evaluate the immunogenicity of mezagitamab.

This clinical trial enrolled a total of **98 participants** diagnosed with **chronic primary immune thrombocytopenia** (ITP). The study population included both **male and female** adults aged **18 years and older**. Participants were required to have a confirmed diagnosis of primary ITP persisting for at least 12 months, with diagnostic criteria aligned with established international guidelines. The trial population was selected based on evidence of insufficient response or intolerance to at least one first-line therapy, such as **corticosteroids**, and at least one second-line therapy, including **thrombopoietin receptor agonists** (TPO-RA), **rituximab**, **fostamatinib**, or **mycophenolate**. Eligible participants demonstrated a mean **platelet count** of less than 30,000/µL from at least two consecutive measurements taken at least five days apart during screening. Prior response to ITP therapy, defined as achieving a platelet count of at least 50,000/µL, was required to support the ITP diagnosis. Participants receiving stable doses of permitted concomitant ITP treatments for at least four weeks prior to enrollment could continue these medications during the trial. The study included a **vulnerable population**.

This is a **Phase 3**, **randomized**, **double-blind**, **placebo-controlled** clinical trial designed to evaluate the efficacy and safety of **mezagitamab** administered via **subcutaneous injection** in participants with **chronic primary immune thrombocytopenia**. The investigational medicinal product, mezagitamab, is a solution for injection containing the active substance mezagitamab, a protein-based therapeutic agent. Participants will be randomized to receive either mezagitamab or a matching placebo. The maximum treatment period is 24 months. The trial is scheduled to begin recruitment in November 2025, with an estimated completion date in December 2027.

The primary objective of this trial is to assess the efficacy of mezagitamab compared with placebo in achieving **durable platelet response** in participants aged 18 years or older with chronic immune thrombocytopenia. The **primary endpoint** is defined as durable platelet response through Week 24, specifically a **platelet count** of at least 50,000/μL on at least 4 of the 6 weekly platelet measurements between Week 19 and Week 24. Secondary endpoints include the cumulative number of weeks with platelet count at or above specified thresholds, time to first platelet count response, complete platelet response defined as platelet count at least 100,000/µL on at least 2 visits through Week 24, changes in quality of life assessed by the **ITP-PAQ** Symptoms scale score at Weeks 16 and 24, occurrence and timing of **rescue therapy**, presence of bleeding events assessed by the **ITP-BAT**, pharmacokinetic parameters including serum concentration of mezagitamab, and immunogenicity assessments including incidence of **anti-drug antibodies** and neutralizing antibodies.

Eligible participants must have been diagnosed with primary immune thrombocytopenia that has persisted for at least 12 months, with diagnosis in accordance with established guidelines. Participants must have evidence of prior response to an immune thrombocytopenia therapy, defined as having achieved a platelet count of at least 50,000/µL. Participants must demonstrate insufficient response or intolerance to at least one currently available first-line therapy such as **corticosteroids** and at least one second-line therapy such as **thrombopoietin receptor agonists**, **rituximab**, **fostamatinib**, or **mycophenolate**. Insufficient response is defined as failure to achieve a sustained platelet count of at least 50,000/µL or doubling of baseline platelet count after an appropriate course of prior treatment. At screening, participants must have a mean platelet count below 30,000/µL with individual values not exceeding 35,000/µL from at least 2 consecutive measurements taken at least 5 days apart, including at least one measurement within 14 days before the first dose. Participants receiving permitted standard-of-care treatment for immune thrombocytopenia at screening may continue such treatment during the trial if the dose and frequency have been stable for at least 4 weeks before receiving the first dose and are expected to remain stable throughout the trial. Permitted concomitant treatments may include one thrombopoietin receptor agonist such as **romiplostim**, **eltrombopag**, **avatrombopag**, or **hetrombopag**, one oral corticosteroid given daily or every other day not exceeding prednisone 20 mg daily or equivalent dose, and fostamatinib.

The trial involves a structured sequence of study visits beginning with a screening period during which eligibility is assessed and baseline measurements are obtained. Following successful screening, participants will attend regular study visits throughout the 24-week treatment period for administration of investigational medicinal product, safety assessments, and efficacy evaluations including weekly platelet count measurements during critical assessment periods. Follow-up visits will be conducted after the treatment period to monitor safety and collect additional data. The end-of-study visit will occur after completion of all protocol-specified assessments. The expected length of participant involvement extends through the treatment period and follow-up phase as defined in the protocol. Conditions that may lead to early termination from the study include withdrawal of consent, safety concerns as determined by the investigator, protocol violations, or other circumstances that would make continued participation inadvisable or not in the participant's best interest.

The experimental treatment in this clinical trial is **Mezagitamab**, also identified by the sponsor product code **TAK-079**. Mezagitamab is formulated as a **solution for injection** containing the active substance mezagitamab, which is classified as a protein of other origin. The medicinal product is manufactured by Takeda Development Center Americas, Inc. The route of administration is via **subcutaneous injection**. The maximum treatment period is 24 months. Specific dosage amounts and frequency of administration are not detailed in the available trial data. This investigational product serves as the test intervention in participants aged 18 years and older with **chronic primary immune thrombocytopenia**.

The comparator treatment utilized in this study is a **placebo** matching Mezagitamab. This placebo is designed to maintain the double-blind nature of the trial by ensuring that participants and investigators remain unaware of treatment allocation. The pharmaceutical form, specific composition, and administration details of the placebo are structured to match the experimental intervention, thereby minimizing bias in the assessment of efficacy and safety outcomes. The placebo serves as the control arm against which the therapeutic effect of mezagitamab is evaluated in achieving durable platelet response in the study population.

Efficacy will be assessed using platelet count measurements and patient-reported outcomes. The primary endpoint is durable platelet response through Week 24, defined as **platelet count** ≥50,000/μL on at least 4 of the 6 weekly platelet measurements between Week 19 and Week 24. Secondary efficacy endpoints include the cumulative number of weeks that a platelet count was ≥50,000/μL through Week 24, time to first platelet count ≥50,000/μL, the cumulative number of weeks that a platelet count was ≥30,000/μL through Week 24 and at least doubled from baseline, complete platelet response defined as a platelet count ≥100,000/µL on at least 2 visits through Week 24, and platelet response at Week 16 defined as a platelet count ≥50,000/µL before investigational medicinal product administration at the Week 16 visit. Change from baseline in the Symptoms scale score of the **ITP-PAQ** will be evaluated at Week 16 and Week 24. Additional secondary endpoints include the occurrence of receiving rescue therapy, time to first rescue therapy, and presence of bleeding events defined as Grade ≥2 in the Skin domain, or Grade ≥1 in the Mucosal domain, or Grade ≥1 in the Organ domain, in the **ITP-BAT** through Week 24. The serum concentration of mezagitamab during and after intervention, incidence of **anti-drug antibodies** and change in anti-drug antibody titers, and incidence of neutralizing anti-drug antibodies will also be assessed as secondary endpoints.