A Phase 2, Randomized, Placebo-Controlled Study to Evaluate Safety, Tolerability, and Efficacy of TAK-079 in Patients With Generalized Myasthenia Gravis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 36
- 试验地点
- 49
- 主要终点
- Percentage of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Grade 3 or Higher TEAEs, and Adverse Event (AE) Leading to TAK-079 Discontinuation
研究概览
简要总结
Myasthenia gravis is an autoimmune condition that causes muscle weakness. Autoimmune means the body makes antibodies that attack its own cells and tissues. These types of antibodies are also known as autoantibodies. People with generalized myasthenia gravis have a weakness in many muscles.
TAK-079 is a medicine to help people with generalized myasthenia gravis.
The main aim of this study is to check if people with generalized myasthenia gravis have side effects from 2 doses of TAK-079. Other aims are to learn if TAK-079 improves their clinical condition and lowers their autoantibody levels.
At the first visit, the study doctor will check if each person can take part. For those who can take part, participants will continue with their standard medicines for this condition during the study. Each participant will have a check-up by the study doctor.
Then, the participants will have 1 of 3 treatments:
- A low dose of TAK-079.
- A high dose of TAK-079.
- A placebo. In this study, a placebo looks like TAK-079 but does not have any medicine in it.
Participants will not know which treatment they received, nor will their study doctors. This is to help make sure the results are more reliable.
For each treatment, participants will receive injections just under the skin, once a week for 8 weeks. The study doctors will check for side effects from the study treatments. The study doctors can stop or delay the injections in each participant if needed.
Then, the study doctors will continue to check for side effects for up to 24 weeks after treatment. They will also check the clinical condition of the participants, including their autoantibody levels.
详细描述
Myasthenia gravis (MG) is an autoimmune disorder in which autoantibodies, such as those targeting the nicotinic acetylcholine receptor (AChR) or muscle specific kinase (MuSK), interfere with neuromuscular transmission, resulting in fatigue and weakness.
The drug being tested in this study is called TAK-079. TAK-079 is being tested to treat people who have generalized myasthenia gravis.
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
- •Diagnosis of Myasthenia Gravis (MG) supported by a positive serologic test for anti-AChR or anti-MuSK antibodies at screening.
- •Myasthenia Gravis Foundation of America (MGFA) clinical classification II to IV at screening.
- •Myasthenia Gravis Activities of Daily Living (MG-ADL) total score of 6 or greater at screening, with at least 4 points attributed to nonocular items.
- •If receiving immunosuppressive drugs (ie, mycophenolate mofetil, methotrexate, cyclosporine, tacrolimus, cyclophosphamide), therapy must be ongoing for at least 6 months, with stable dosing ongoing for at least 3 months before screening. Participants receiving azathioprine must be on a stable dose for at least 6 months before screening.
- •If receiving oral corticosteroids, therapy must be ongoing for at least 3 months, with a stable dose at least 1 month before screening. Corticosteroids, including dexamethasone, must be given as oral, daily or every-other-day therapy, as opposed to pulse therapy.
- •If receiving cholinesterase inhibitors, therapy with a stable dose is required at least 2 weeks before screening.
- •The doses of concomitant standard background therapy must be expected to remain stable throughout the study unless dose reduction is required due to toxicities. Allowed background therapy is defined as no more than a cholinesterase inhibitor ± corticosteroid ± 1 steroid-sparing immunosuppressive drug (limited to azathioprine, mycophenolate mofetil, methotrexate, cyclosporine, tacrolimus, or cyclophosphamide). Participants must be on at least one allowed background medication.
排除标准
- •Presence of a thymoma (previous history of a fully encapsulated thymoma removed ≥ 12 months before screening is allowed) or history of invasive thymic malignancy unless deemed cured by adequate treatment with no evidence of recurrence for ≥ 5 years before screening.
- •History of thymectomy within 12 months before screening.
- •MGFA class I or V.
- •Received intravenous immunoglobulin (IVIg), subcutaneous immunoglobulin (SCIg), or plasmapheresis/plasma exchange within 4 weeks before screening, or an expectation that any therapy besides the participants standard background therapies may be used for treatment of MG (eg, a rescue therapy) between screening and dosing.
- •Chronic obstructive pulmonary disease (COPD) or asthma with a pre-bronchodilatory forced expiratory volume in 1 second (FEV1) <50% of predicted normal.
- •Note: FEV1 testing is required for participants suspected of having COPD or asthma.
- •Received rituximab, belimumab, eculizumab, or any monoclonal antibody for immunomodulation within 6 months before first dosing. Participants with prior exposure to rituximab must have CD19 counts within the normal range at screening.
- •Known autoimmune disease other than MG that could interfere with the course and conduct of the study.
- •Received a live vaccine within 4 weeks before screening or has any live vaccination planned during the study.
- •Opportunistic infection ≤12 weeks before initial study dosing or currently receiving treatment for a chronic opportunistic infection, such as tuberculosis (TB), pneumocystis pneumonia, cytomegalovirus, herpes simplex virus, herpes zoster, or atypical mycobacteria. A mild, localized herpes simplex infection within 12 weeks of study dosing is allowed, as long as the lesion has resolved without systemic therapy prior to Day 1.
研究组 & 干预措施
TAK-079 Placebo-matching
TAK-079 placebo-matching injection, subcutaneously (SC), once weekly in combination with standard background therapy for 8 weeks.
干预措施: TAK-079 Placebo (Drug)
TAK-079 300 mg
TAK-079 300 mg injection, SC, once weekly in combination with standard background therapy for 8 weeks.
干预措施: TAK-079 (Drug)
TAK-079 600 mg
TAK-079 600 mg injection, SC, once weekly in combination with standard background therapy for 8 weeks.
干预措施: TAK-079 (Drug)
结局指标
主要结局
Percentage of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Grade 3 or Higher TEAEs, and Adverse Event (AE) Leading to TAK-079 Discontinuation
时间窗: From signing the informed consent form up to end of long-term follow-up (up to Week 32)
AE is defined as any untoward medical occurrence in clinical investigation participant administered drug; it does not necessarily have to have causal relationship with this treatment. TEAE is defined as AE with onset that occurs after receiving study drug. SAE is an adverse event resulting in any of following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Severity of TEAEs was graded using National cancer institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 definitions of Grade 1 through Grade 5 wherein Grade 1=mild symptoms, Grade 2=moderate symptoms, Grade 3=Severe or medically significant but not immediately life-threatening, Grade 4=life-threatening consequences and Grade 5=death related to AEs. Percentages are rounded off to whole number at single decimal.
次要结局
- Change From Baseline in Myasthenia Gravis Activities of Daily Living (MG-ADL) Scale Score(Baseline up to Week 32)
- Percentage of Participants With 2-point Reduction in MG-ADL Total Score(At Weeks 4, 6, 8, 10, 12, 14, 16, 20, 24, 28 and 32)
- Change From Baseline in Quantitative Myasthenia Gravis (QMG) Scale Score(Baseline up to Week 32)
- Percentage of Participants With 3-point Reduction in QMG Total Score(At Weeks 4, 6, 8, 10, 12, 14, 16, 20, 24, 28 and 32)
- Change From Baseline in Myasthenia Gravis Composite (MGC) Scale Score(Baseline up to Week 32)
- Change From Baseline in Anti-acetylcholine Receptor (AChR) Antibody Levels(Baseline up to Week 32)
- Percentage of Participants With 3-point Reduction in MGC Total Score(At Weeks 4, 6, 8, 10, 12, 14, 16, 20, 24, 28 and 32)
- Change From Baseline in Revised 15-item Myasthenia Gravis Quality of Life Scale (MG-QoL15r) Scale Score(Baseline up to Week 32)
- Change From Baseline in Anti- Muscle-specific Tyrosine Kinase (MuSK) Titer Levels(Baseline up to Week 32)