Clinical trial NCT06722235: A Study of Mezagitamab in Adults With Chronic Primary Immune Thrombocytopenia
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Immune Thrombocytopenic Purpura (ITP)
Keywords: Thrombocytopenia
TAK-079
Blood Platelet Disorders
Hematologic Diseases
Cytopenia
Purpura
Hemorrhagic Disorders
Autoimmune Diseases
Immune System Diseases
Hemorrhage
Skin Manifestations
Purpura, Thrombocytopenic, Idiopathic
Purpura, Thrombocytopenic
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2024-12-09
Enrollment: 171
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Primary immune thrombocytopenia (ITP) is a condition where the immune system mistakenly destroys platelets, which are cells that help stop bleeding. This leads to a low number of platelets, making it easier to bruise or bleed. The main aim of this study is to learn whether mezagitamab, when given just under the skin (subcutaneously \[SC\]), is effective in keeping the platelet count of adults with ITP stable when compared to a placebo. A placebo looks like medicine but doesn't have any active ingredients in it.

The participants will be treated with mezagitamab for up to 6 months.

During the study, participants will visit their study clinic several times.

Participants who complete the TAK-079-3002 study or do not have any response to study treatment by week 16 (according to study criteria) will be given the opportunity to participate in a continuation study to receive open label mezagitamab (if they are eligible and the site is able to open the continuation study).


Eligibility criteria: Key Inclusion Criteria:

1. The participant has been diagnosed with ITP that has persisted for at least 12 months.
2. 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/μL.
3. 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/μL 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.
4. The participant has a mean platelet count of \<30,000/μL.
5. 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.
6. 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.

Key Exclusion Criteria:

1. The participant has secondary ITP.
2. The participant has had any thrombotic or embolic event within 12 months before signing the informed consent form (ICF).
3. The participant has had a splenectomy within 3 months before signing the ICF.
4. The participant has active infection with hepatitis B virus, hepatitis C virus, or human immunodeficiency virus (HIV).
5. 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.
6. 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.
7. The participant has received anti-cluster of differentiation (CD)20 treatment within 12 months before screening, and either of the following applies:

   1. The last dose was received within 6 months before screening.
   2. 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.
8. The participant has received any monoclonal or polyclonal antibody for immunomodulation within 6 months before Day 1.
9. 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.
10. The participant has used anticoagulants (e.g., vitamin K antagonists, direct oral anticoagulants) within 3 weeks prior to the first dose of trial treatment.
11. 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.
12. 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.
13. 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.
14. 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 inclusion/exclusion criteria may apply.

Primary outcomes:
measure: Percentage of Participants with Durable Platelet Response
timeFrame: Up to Week 24
Secondary outcomes:
measure: Cumulative Number of Weeks with a Platelet Count of ≥50,000/μL
timeFrame: Up to Week 24
measure: Time to First Platelet Count ≥50,000/μL
timeFrame: Up to Week 24
measure: The Cumulative Number of Weeks with a Platelet Count of ≥30,000/μL
timeFrame: Up to Week 24
measure: Percentage of Participants with Complete Platelet Response
timeFrame: Up to Week 24
measure: Percentage of Participants with Platelet Response at Week 16
timeFrame: Week 16
measure: Change from Baseline in the Symptoms Domain Score of the Immune Thrombocytopenia Patient Assessment Questionnaire (ITP-PAQ) at Weeks 16 and 24
timeFrame: Weeks 16 and 24
measure: Percentage of Participants Receiving Rescue Therapy
timeFrame: Up to Week 24
measure: Time to First Rescue Therapy
timeFrame: Up to Week 24
measure: Percentage of Participants with Bleeding Events
timeFrame: Up to Week 24
measure: Serum Concentration of Mezagitamab During and After Intervention
timeFrame: Predose on Day 1 and at multiple time points post-dose up to Day 169
measure: Number of Participants with Anti-drug Antibodies (ADA)
timeFrame: Predose on Day 1 and at multiple time points post-dose up to Day 169
measure: Change in ADA Titers Over Time
timeFrame: Up to Day 169
measure: Number of Participants with Neutralizing ADA
timeFrame: Predose on Day 1 and at multiple time points post-dose up to Day 169
Other outcomes:
Locations:
city: Shijiazhuang
country: China
facility: The First Hospital of Hebei Medical University
state: Hebei
city: Wuhan
country: China
facility: Union Hospital Tongji Medical College Huazhong University of Science and Technology
state: Hebei
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University - Donghu Campus
state: Jiangxi
city: Shanghai
country: China
facility: Jinshan Hospital of Fudan University
state: Shanghai
city: Chuo-ku
country: Japan
facility: Chiba Aoba Municipal Hospital
state: Chiba
city: Itabashi-ku
country: Japan
facility: Nihon University Itabashi Hospital
state: Tokyo
city: Sumida-ku
country: Japan
facility: Tokyo Metropolitan Bokutoh Hospital
state: Tokyo
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: