Immune Thrombocytopenic Purpura (ITP)
Conditions
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
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).
Interventions
DRUGMezagitamab
Mezagitamab injection administered SC.
DRUGPlacebo
Mezagitamab placebo-matching injection administered SC.
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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. 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants with Durable Platelet Response | Up to Week 24 | Durable platelet response is defined as platelet count greater than or equal to (≥)50,000/microliter (μL) on at least 4 of the 6 weekly platelet measurements between Weeks 19 and 24. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Number of Weeks with a Platelet Count of ≥50,000/μL | Up to Week 24 | The cumulative number of weeks in which the platelet count is ≥50,000/μL through Week 24. |
| Time to First Platelet Count ≥50,000/μL | Up to Week 24 | — |
| The Cumulative Number of Weeks with a Platelet Count of ≥30,000/μL | Up to Week 24 | The cumulative number of weeks in which the platelet count is ≥30,000/μL, 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/μL 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/μL 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 Weeks 16 and 24 | Weeks 16 and 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 Receiving Rescue Therapy | Up to Week 24 | — |
| 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. |
| Serum Concentration of Mezagitamab During and After Intervention | Predose on Day 1 and at multiple time points post-dose up to Day 169 | — |
| Number of Participants with Anti-drug Antibodies (ADA) | Predose on Day 1 and at multiple time points post-dose up to Day 169 | — |
| Change in ADA Titers Over Time | Up to Day 169 | — |
| Number of Participants with Neutralizing ADA | Predose on Day 1 and at multiple time points post-dose up to Day 169 | — |
Countries
Australia, Bulgaria, China, Croatia, Greece, Hong Kong, Italy, Japan, Netherlands, Poland, South Korea, Spain, Turkey (Türkiye), United Kingdom, United States
Contacts
CONTACTTakeda Contact
STUDY_DIRECTORStudy Director
Takeda
Outcome results
None listed