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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 41
- 试验地点
- 55
- 主要终点
- 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 Discontinuation
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Part A & B: Double Blind Period: Placebo
Participants 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.
干预措施: Placebo (Drug)
Part A: Double Blind Period: TAK-079 100 mg
Participants 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.
干预措施: TAK-079 (Drug)
Part A: Double Blind Period: TAK-079 300 mg
Participants 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.
干预措施: TAK-079 (Drug)
Part B: Double Blind Period: TAK-079 600 mg
Participants 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.
干预措施: TAK-079 (Drug)
Part A: Open-label Extension (OLE) Period: TAK-079 100 mg
Participants 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.
干预措施: TAK-079 (Drug)
Part A: OLE Period: TAK-079 300 mg
Participants 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.
干预措施: TAK-079 (Drug)
Part B: OLE Period: TAK-079 600 mg
Participants 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.
干预措施: TAK-079 (Drug)
结局指标
主要结局
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 Discontinuation
时间窗: Up 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.
次要结局
- Percentage of Participants With Platelet Response at Weeks 16 and 32(At Weeks 16 and 32)
- Percentage of Participants With Complete Platelet Response at Weeks 16 and 32(At Weeks 16 and 32)
- Percentage of Participants With Clinically Meaningful Platelet Response at Weeks 16 and 32(At Weeks 16 and 32)
- Percentage of Participants With Hemostatic Platelet Response at Weeks 16 and 32(At Weeks 16 and 32)