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

Phase 2
Completed
Conditions
Primary Immune Thrombocytopenia
Interventions
Drug: Placebo
Registration Number
NCT04278924
Lead Sponsor
Takeda
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
41
Inclusion Criteria
  1. 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.

  2. 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.

  3. 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.

  4. If receiving standard background treatment for ITP, treatment should be stable in dose and frequency for at least 4 weeks before dosing.

    1. 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.
    2. 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
  1. Use of anticoagulants or any drug with antiplatelet effect (such as aspirin) within 3 weeks before screening.
  2. Has a history of any thrombotic or embolic event within 12 months before screening.
  3. Has a history of splenectomy within 3 months before screening.
  4. 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.
  5. Diagnosed with chronic obstructive pulmonary disease (COPD) or asthma, and a prebronchodilatory forced expiratory volume in 1 second (FEV1) <50% of predicted normal.
  6. 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.
  7. Use of immunosuppressants (such as cyclophosphamide, vincristine) other than permitted oral immunosuppressants within 6 months before first dosing.
  8. Has been diagnosed with myelodysplastic syndrome.
  9. 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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Part A & B: Double Blind Period: PlaceboPlaceboParticipants received TAK-079 placebo-matching injection subcutaneously (SC), once weekly (QW) for 8 weeks. Following treatment participants were followed up for 8 weeks in a double blinded short follow-up period (SFP) up to Week 16. Participants who opted to receive treatment with TAK-079 were then randomized to receive TAK-079, SC injection, QW for 8 weeks in Open-label Extension (OLE) Period of Part A or Part B. Participants who did not opt to receive treatment with TAK-079 were followed up for another 16 weeks in an unblinded long follow-up period (LFP) up to Week 32.
Part A: Double Blind Period: TAK-079 100 mgTAK-079Participants received TAK-079 100 mg, SC injection, QW for 8 weeks. Following treatment participants were followed up for 8 weeks in a double blinded SFP up to Week 16. Participants who opted to receive treatment with TAK-079 were then randomized to receive TAK-079, SC injection, QW for 8 weeks in OLE Period of Part A or Part B. Participants who did not opt to receive treatment with TAK-079 were followed up for another 16 weeks in an unblinded LFP up to Week 32.
Part A: Double Blind Period: TAK-079 300 mgTAK-079Participants received TAK-079 300 mg, SC injection, QW for 8 weeks. Following treatment participants were followed up for 8 weeks in a double blinded SFP up to Week 16. Participants who opted to receive treatment with TAK-079 were then randomized to receive TAK-079, SC injection, QW for 8 weeks in OLE Period of Part A or Part B. Participants who did not opt to receive treatment with TAK-079 were followed up for another 16 weeks in an unblinded LFP up to Week 32.
Part B: Double Blind Period: TAK-079 600 mgTAK-079Participants received TAK-079 600 mg, SC injection, QW for 8 weeks. Following treatment participants were followed up for 8 weeks in a double blinded SFP up to Week 16. Participants who opted to receive treatment with TAK-079 were then randomized to receive TAK-079, SC injection, QW for 8 weeks in OLE Period of Part A or Part B. Participants who did not opt to receive treatment with TAK-079 were followed up for another 16 weeks in an unblinded LFP up to Week 32.
Part A: Open-label Extension (OLE) Period: TAK-079 100 mgTAK-079Participants who received placebo in double-blind Part A and opted to receive treatment with TAK-079 were randomized to receive TAK-079 100 mg, SC injection, QW for 8 weeks in OLE Period of Part A. Following treatment participants were followed up for 8 weeks in a SFP and then for another 16 weeks in a LFP.
Part A: OLE Period: TAK-079 300 mgTAK-079Participants who received placebo in double-blind Part A and opted to receive treatment with TAK-079 were randomized to receive TAK-079 300 mg, SC injection, QW for 8 weeks in OLE Period of Part A. Following treatment participants were followed up for 8 weeks in a SFP and then for another 16 weeks in a LFP.
Part B: OLE Period: TAK-079 600 mgTAK-079Participants who received placebo in double-blind Part B and opted to receive treatment with TAK-079 received TAK-079 600 mg, SC injection, QW for 8 weeks in OLE Period of Part B. Following treatment participants were followed up for 8 weeks in a SFP and then for another 16 weeks in a LFP.
Primary Outcome Measures
NameTimeMethod
Percentage of Participants With at Least One Grade 3 or Higher Treatment Emergent Adverse Event (TEAE), Treatment Emergent Serious Adverse Event (SAE), and TEAEs Leading to TAK-079 DiscontinuationUp to Week 32 in each Period of the study

An adverse event (AE) was defined as any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with the treatment. SAE means any untoward medical occurrence that at any dose: a) results in death; b) is life-threatening; c) requires inpatient hospitalization or prolongation of an existing hospitalization; d) results in persistent or significant disability or incapacity; e) is a congenital anomaly/birth defect; f) is a medically important event. TEAEs were defined as an AE having a start date and time equal to or later than the start date and time of the first dose of investigational medicinal product (IMP). Percentages were rounded off to the nearest single decimal place.

Secondary Outcome Measures
NameTimeMethod
Percentage of Participants With Platelet Response at Weeks 16 and 32At Weeks 16 and 32

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. Percentages were rounded off to the nearest single decimal place.

Percentage of Participants With Complete Platelet Response at Weeks 16 and 32At Weeks 16 and 32

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. Percentages were rounded off to the nearest single decimal place.

Percentage of Participants With Clinically Meaningful Platelet Response at Weeks 16 and 32At Weeks 16 and 32

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. Percentages were rounded off to the nearest single decimal place.

Percentage of Participants With Hemostatic Platelet Response at Weeks 16 and 32At Weeks 16 and 32

A hemostatic platelet response is defined for participants with a baseline platelet count of \<15,000/μL who achieved 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. Percentages were rounded off to the nearest single decimal place.

Trial Locations

Locations (55)

Arizona Clinical Research Center - Hunt - PPDS

🇺🇸

Tucson, Arizona, United States

University of Florida

🇺🇸

Gainesville, Florida, United States

Bleeding and Clotting Disorders Institute

🇺🇸

Peoria, Illinois, United States

Massachusetts General Hospital

🇺🇸

Boston, Massachusetts, United States

Boston Medical Center

🇺🇸

Boston, Massachusetts, United States

Leo W. Jenkins Cancer Center

🇺🇸

Greenville, North Carolina, United States

University of Virginia

🇺🇸

Charlottesville, Virginia, United States

Acibadem City Clinic Multiprofile Hospital for Active Treatment Tokuda

🇧🇬

Sofia, Sofia-Grad, Bulgaria

University Multiprofile Hospital for Active Treatment Sofiamed OOD

🇧🇬

Sofia, Sofia-Grad, Bulgaria

University Multiprofile Hospital for Active Treatment - Dr. Georgi Stranski EAD

🇧🇬

Pleven, Bulgaria

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Arizona Clinical Research Center - Hunt - PPDS
🇺🇸Tucson, Arizona, United States
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