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
- Conditions
- Immune Thrombocytopenic Purpura (ITP)
- Registration Number
- jRCT2031240667
- Lead Sponsor
- Takeda Pharmaceutical Company Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- All
- Target Recruitment
- 171
- The participant has been diagnosed with ITP that has persisted for at least 12 months.
- The participant's diagnosis of ITP is supported by a prior response to an ITP therapy (not including a thrombopoietin receptor agonist [TPO-RA]), defined as having achieved a platelet count >=50,000/microliter.
- The participant has evidence of insufficient response or intolerance to at least 1 currently available first-line therapy for treatment of ITP (for example, corticosteroids), and at least 1 currently available second-line therapy for treatment of ITP (for example, TPO-RA, rituximab, fostamatinib, mycophenolate). Insufficient response to previous treatment is defined as failure to achieve a sustained platelet count of at least 50,000/microliter or doubling of baseline platelet count after an appropriate course of prior ITP treatment. Intolerance is defined as a documented side effect causing discontinuation of the therapy.
- The participant has a mean platelet count of <30,000/microliter.
- If the participant is receiving allowed standard-of-care treatment for ITP at screening, and continued use is intended, treatment may continue during the trial if the dose, and frequency have been stable for at least 4 weeks before receiving the first dose of IMP (i.e., Day 1), and are expected to remain stable throughout the trial.
- If the participant is an individual with potential for pregnancy, the participant is not pregnant as confirmed by negative human chorionic gonadotropin during screening, and before the first dose of trial intervention. Other protocol defined inclusion criteria may apply.
- The participant has secondary ITP.
- The participant has had any thrombotic or embolic event within 12 months before signing the informed consent form (ICF).
- The participant has had a splenectomy within 3 months before signing the ICF.
- The participant has active infection with hepatitis B virus, hepatitis C virus, or human immunodeficiency virus (HIV).
- History of malignancy (including myelodysplastic syndrome) within 5 years of signing the ICF, except for treated non-melanoma skin cancer or cervical carcinoma in situ.
- In the opinion of the investigator, the participant has a serious medical or psychiatric illness that could potentially interfere with the completion of treatment according to this protocol.
- The participant has received anti-cluster of differentiation (CD)20 treatment within 12 months before screening, and either of the following applies:
- The last dose was received within 6 months before screening.
- The last dose was received between 6, and 12 months before screening, and the participant has a cluster of differentiation 19 positive (CD19+) count below the lower limit of normal.
- The participant has received any monoclonal or polyclonal antibody for immunomodulation within 6 months before Day 1.
- The participant has any prior exposure to mezagitamab or has been exposed to another investigational agent within 4 weeks or 5 half-lives, whichever is longer, before Day 1.
- The participant has used anticoagulants (e.g., vitamin K antagonists, direct oral anticoagulants) within 3 weeks prior to the first dose of trial treatment.
- The participant has received a live or live-attenuated vaccine within 4 weeks prior to the first dose of trial treatment or has any live or live-attenuated vaccine planned during the trial.
- The participant has used the following immunosuppressive agents as specified prior to the first dose of trial treatment: alkylating agents (e.g., cyclophosphamide) within 8 weeks, vinca alkaloids (e.g., vincristine) within 4 weeks, sulfones (e.g., dapsone) within 3 weeks, antiproliferative agents: (e.g., mycophenolate mofetil, and azathioprine) within 2 weeks, and calcineurin inhibitors: (e.g., cyclosporine) within 2 weeks.
- The participant has used intravenous immunoglobulin (IVIg), SC immunoglobulin, recombinant human thrombopoietin, anti-D immunoglobulin treatment, or efgartigimod within 4 weeks before signing the ICF or it is expected that any treatment for thrombocytopenia other than the participant's standard-of-care ITP therapy (e.g., rescue therapy, administration of blood products) may be used between screening, and Day 1.
- The participant has a history of severe allergic or anaphylactic reactions to recombinant proteins or excipients used in the mezagitamab/placebo formulation. Other protocol defined exclusion criteria may apply.
Study & Design
- Study Type
- Interventional
- Study Design
- parallel assignment
- Primary Outcome Measures
Name Time Method - 1. Percentage of Participants with Durable Platelet Response
Time Frame: Up to Week 24
Durable platelet response is defined as platelet count greater than or equal to (>=)50,000/microliter on at least 4 of the 6 weekly platelet measurements between Weeks 19 and 24.
- Secondary Outcome Measures
Name Time Method Cumulative Number of Weeks with a Platelet Count of >=50,000/microliter Up to Week 24 The cumulative number of weeks in which the platelet count is >=50,000/microliter through Week 24.
The Cumulative Number of Weeks with a Platelet Count of >=30,000/microliter Up to Week 24 The cumulative number of weeks in which the platelet count is >=30,000/microliter, and at least doubled from baseline through Week 24.
Percentage of Participants with Complete Platelet Response Up to Week 24 Complete platelet response is defined as a platelet count >=100,000/microliter on at least 2 visits through Week 24.
Percentage of Participants with Platelet Response at Week 16 Week 16 Platelet response is defined as a platelet count >=50,000/microliter before investigational medicinal product (IMP) administration at the Week 16 visit.
Change from Baseline in the Symptoms Domain Score of the Immune Thrombocytopenia Patient Assessment Questionnaire (ITP-PAQ) at Week 24 Week 24 ITP-PAQ is a 44-item participant reported outcome (PRO) measure that assesses disease-specific health-related quality of life (HRQoL) that includes 10 domains: Symptoms, Fatigue/Sleep, Physical Health - Bother, Physical Health - Activity, Emotional Health - Psychological, Emotional Health - Fear, Overall Quality of Life (QoL), Social Activity, Women's Reproductive Health (including Fertility subscale, and Menstrual Symptoms subscale), and Work. The 6-item symptoms domain is scored from 0 to 100, with higher scores representing improvement of symptoms.
Percentage of Participants with Bleeding Events Up to Week 24 Bleeding events are defined as Grade >=2 in the skin domain, or Grade >=1 in the mucosal domain, or Grade >=1 in the organ domain, in the immune thrombocytopenia-specific bleeding assessment tool (ITP-BAT) through Week 24.