A Study of TAK-079 in Adults With Persistent/Chronic Primary Immune Thrombocytopenia

Study Overview
=================
Brief Summary
-----------------
Primary immune thrombocytopenia (ITP) is a rare disease that results in low levels of platelets - the cells that help blood clot. The main aim of the study is to check for side effects from taking TAK-079 at three different dose levels. Another aim is to learn if TAK-079 can increase the platelet count in people with ITP. In addition to receiving stable background therapy for ITP, participants will receive an injection of either TAK-079 or a placebo once a week for 2 months. A placebo looks like TAK-079 but will not have any medicine in it. After treatment, all participants will be followed-up for another 2 months. Then, participants who received TAK-079 will continue to be followed-up for an extra 4 months. Participants who received the placebo and would like to receive TAK-079 may be able to do this in an extension period in the study.

Detailed Description
-----------------
The drug being tested in this study is called TAK-079. TAK-079 is being tested to treat people who have primary immune thrombocytopenia (ITP). This study will evaluate the safety and biologic activity of TAK-079 or matching placebo in combination with stable ITP background therapy. The study will enroll approximately 36 to 54 participants. In Part A of the study, participants will be randomly assigned (by chance, like flipping a coin) to one of the three treatment groups. Those who received placebo in this period will have the choice to receive TAK-079 after a safety follow-up period and will be randomized to one of the two open-label TAK-079 treatment arms. An unblinded safety review will take place once a minimum of 24 evaluable participants are available for analysis in Part A to decide whether to open enrollment into Part B. In Part B participants will be randomly assigned to one of two treatment groups. Those who received placebo in this period will have the choice to receive study drug after a safety follow-up period in a single open-label TAK-079 treatment arm. This multi-center trial will be conducted worldwide. All participants will be followed for at least 8 weeks in a Safety Follow-up Period, and a 16-week Long-term Follow-up Period after the 8 weeks of treatment.

Official Title
-----------------
A Phase 2, Randomized, Double-blind, Placebo-Controlled Study to Evaluate Safety, Tolerability, and Efficacy of TAK-079 in Patients With Persistent/Chronic Primary Immune Thrombocytopenia

Conditions
-----------------
Primary Immune Thrombocytopenia

Intervention / Treatment
-----------------
* Drug: Placebo
* Drug: TAK-079


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosed with ITP that has persisted for ≥3 months, diagnosed in accordance to The American Society of Hematology 2011 Evidence-based Practice Guideline for Immune Thrombocytopenia or the International Consensus Report on The Investigation and Management of Primary Immune Thrombocytopenia as locally applicable. Has a mean platelet count of <30,000/μL (and individually ≤35,000/μL) on at least 2 measurements at least 1 week apart during screening. Diagnosis of ITP supported by a prior response to an ITP therapy (other than a thrombopoietin receptor agonists [TPO-RA]) that achieved a platelet count of ≥50,000/μL. If receiving standard background treatment for ITP, treatment should be stable in dose and frequency for at least 4 weeks before dosing. Permitted standard background treatments may include: 1 oral corticosteroid; ±1 immunosuppressant from the following list: azathioprine, danazol, dapsone, cyclosporine, mycophenolate mofetil, mycophenolate sodium; ±1 TPO-RA (romiplostim, eltrombopag, avatrombopag); ±fostamatinib. Corticosteroids, including dexamethasone, must be given as oral, daily or every-other-day therapy as opposed to pulse therapy. The dose of any permitted standard background therapy must be expected to remain stable through the study, unless dose reduction is required because of toxicities. Exclusion Criteria: Use of anticoagulants or any drug with antiplatelet effect (such as aspirin) within 3 weeks before screening. Has a history of any thrombotic or embolic event within 12 months before screening. Has a history of splenectomy within 3 months before screening. Use of intravenous immunoglobulin (IVIg), subcutaneous immunoglobulin or anti-D immunoglobulin treatment within 4 weeks of screening, or an expectation that any therapy besides the participant's standard background therapies may be used for treatment of thrombocytopenia (e.g., a rescue therapy) between screening and dosing. Diagnosed with chronic obstructive pulmonary disease (COPD) or asthma, and a prebronchodilatory forced expiratory volume in 1 second (FEV1) <50% of predicted normal. Use of rituximab or any monoclonal antibody (mAb) for immunomodulation within 4 months before first dosing. Note: Participants with prior exposure to rituximab must have cluster of differentiation (CD) 19 counts within the normal range at screening. Use of immunosuppressants (such as cyclophosphamide, vincristine) other than permitted oral immunosuppressants within 6 months before first dosing. Has been diagnosed with myelodysplastic syndrome. Has received a live vaccine within 4 weeks before screening or has any live vaccine planned during the study. 10 Has had an opportunistic infection ≤12 weeks before initial study dosing or is currently undergoing treatment for a chronic opportunistic infection, such as tuberculosis (TB), pneumocystis pneumonia, cytomegalovirus, herpes simplex virus, herpes zoster, or atypical mycobacteria.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Part A: Double Blind, Placebo<br>TAK-079 placebo-matching injection subcutaneously (SC) once weekly (QW) for 8 weeks. | Drug: Placebo<br>* TAK-079 placebo-matching SC injection.<br>|
| Experimental: Part A: Double Blind, TAK-079 Dose 1<br>TAK-079 Dose 1, SC injection QW for 8 weeks. | Drug: TAK-079<br>* TAK-079 SC injection.<br>|
| Experimental: Part A: Double Blind, TAK-079 Dose 2<br>TAK-079 Dose 2, SC injection QW for 8 weeks. | Drug: TAK-079<br>* TAK-079 SC injection.<br>|
| Experimental: Part A: Open-label Extension (OLE) Phase, TAK-079 Dose 1<br>Participants who received placebo in double-blind Part A and opt to receive further treatment will be randomized to receive TAK-079 Dose 1, SC injection QW for 8 weeks in OLE Phase of Part A. | Drug: TAK-079<br>* TAK-079 SC injection.<br>|
| Experimental: Part A: OLE Phase, TAK-079 Dose 2<br>Participants who received placebo in double-blind Part A and opt to receive further treatment will be randomized to receive TAK-079 Dose 2, SC injection QW for 8 weeks in OLE Phase of Part A. | Drug: TAK-079<br>* TAK-079 SC injection.<br>|
| Placebo Comparator: Part B: Double Blind, Placebo<br>TAK-079 placebo-matching injection SC, QW for 8 weeks. | Drug: Placebo<br>* TAK-079 placebo-matching SC injection.<br>|
| Experimental: Part B: Double Blind, TAK-079 Dose 3<br>TAK-079 Dose 3, SC injection QW for 8 weeks. | Drug: TAK-079<br>* TAK-079 SC injection.<br>|
| Experimental: Part B: OLE Phase, TAK-079 Dose 3<br>Participants who received placebo in double-blind Part B and opt to receive further treatment will receive TAK-079 Dose 3, SC injection QW for 8 weeks in OLE Phase of Part B. | Drug: TAK-079<br>* TAK-079 SC injection.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with at Least One Grade 3 or Higher Treatment Emergent Adverse Event (TEAE), Serious Adverse Event (SAE), and Adverse Event (AE) Leading to TAK-079 Discontinuation |  | From the first dose of study drug up to Week 32 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with Platelet Response | Platelet response is defined as a platelet count ≥50,000/microliter (μL) and ≥20,000/μL above baseline on at least 2 visits without a dosing period-permitted rescue treatment in the previous 4 weeks and without any other previous rescue therapy. | Up to Week 32 | 
| Percentage of Participants with Complete Platelet Response | Complete platelet response is defined as a platelet count ≥100,000/μL on at least 2 visits without a dosing period-permitted rescue treatment in the previous 4 weeks and without any other previous rescue therapy. | Up to Week 32 | 
| Percentage of Participants with Clinically Meaningful Platelet Response | A clinically meaningful platelet response is defined as a platelet count ≥20,000/μL above baseline on at least 2 visits without a dosing period-permitted rescue treatment in the previous 4 weeks and without any other previous rescue therapy. | Up to Week 32 | 
| Percentage of Participants with Hemostatic Platelet Response | A hemostatic platelet response is defined for participants with a baseline platelet count of <15,000/μL who achieve a platelet count of ≥30,000/μL and ≥20,000/μL above baseline on at least 2 visits without a dosing period-permitted rescue treatment in the previous 4 weeks and without any other previous rescue therapy. | Up to Week 32 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Drug Therapy