Prospective, Double-blind, Randomized, Placebo-Controlled Phase III Study Evaluating Efficacy and Safety of Octagam 10% in Patients With Dermatomyositis ("ProDERM Study")
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Octapharma
- 入组人数
- 95
- 试验地点
- 21
- 主要终点
- Measure the Number of Patients Who Had an Increase of ≥20 Points on the Total Improvement Score (TIS)
研究概览
简要总结
Prospective, Double-blind, Randomized, Placebo-Controlled Phase III Study Evaluating Efficacy and Safety of Octagam 10% in Patients With Dermatomyositis ("ProDERM study")
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 79 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects with diagnosis of definite or probable DM according to the Bohan and Peter criteria.
- •Subjects under treatment with corticosteroids and/or maximally 2 immune-suppressants and being on stable therapy for at least 4 weeks (see Section 4.2.1) OR Subjects with previous failure of response or previous intolerance to corticosteroid and at least 1 additional immunosuppressive drug, and with steroid/immunosuppressive drugs washed out as per Section 4.2.1 (Table 2).
- •Subjects with active disease, assessed and agreed upon by an independent adjudication committee.
- •Manual Muscle Testing-8 (MMT-8) score <142, with at least 2 other abnormal Core Set Measures (CSM) (Visual Analogue Scale [VAS] of patient global activity ≥2 cm, physician's global disease activity ≥2 cm, extra-muscular activity ≥2 cm; at least one muscle enzyme >1.5 times upper limit of normal, Health Assessment Questionnaire ≥0.25).
- •Males or females ≥ 18 to < 80 years of age.
- •Voluntarily given, fully informed written consent obtained from subject before any study-related procedures are conducted.
- •Subject must be capable to understand and comply with the relevant aspects of the study protocol.
排除标准
- •Cancer-associated myositis, defined as the diagnosis of myositis within 2 years of the diagnosis of cancer (except basal or squamous cell skin cancer or carcinoma in situ of the cervix that has been excised and cured and at least 1 or 5 years, respectively, have passed since excision).
- •Evidence of active malignant disease or malignancies diagnosed within the previous 5 years (including hematological malignancies and solid tumors) or breast cancer diagnosed within the previous 10 years.
- •Subjects with overlap myositis (except for overlap with Sjögren's syndrome), connective tissue disease associated DM, inclusion body myositis, polymyositis, juvenile dermatomyositis or drug-induced myopathy.
- •Subjects with immune-mediated necrotizing myopathy with absence of typical DM rash.
- •Subjects with generalized, severe musculoskeletal conditions other than DM that prevent a sufficient assessment of the subject by the physician.
- •Subjects who have received IgG treatment within the last 6 months before enrolment.
- •Subjects who received blood or plasma-derived products (other than IgG) or plasma exchange within the last 3 months before enrolment.
- •Subjects starting or planning to start a physical therapy-directed exercise regimen during the trial.
- •Cardiac insufficiency (New York Heart Association III/IV), cardiomyopathy, significant cardiac dysrhythmia requiring treatment, unstable or advanced ischemic heart disease.
- •Severe liver disease, with signs of ascites and hepatic encephalopathy.
- •Severe kidney disease (as defined by estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2).
- •Known hepatitis B, hepatitis C or HIV infection.
- •Subjects with a history of TEE such as deep vein thrombosis, pulmonary embolism, myocardial infarction, ischemic stroke, transient ischemic attack, peripheral artery disease (Fontaine IV) ever.
- •Body mass index ≥40 kg/m
- •Medical conditions whose symptoms and effects could alter protein catabolism and/or IgG utilization (e.g. protein-losing enteropathies, nephrotic syndrome).
- •Known IgA deficiency with antibodies to IgA.
- •History of hypersensitivity, anaphylaxis or severe systemic response to immuno-globulin, blood or plasma derived products or any component of Octagam 10%.
- •Known blood hyperviscosity, or other hypercoagulable states.
- •Subjects with a history of drug abuse within the past 5 years prior to study enrollment.
- •Subjects unable or unwilling to understand or comply with the study protocol.
- •Participating in another interventional clinical study with investigational treatment within 3 months prior to study enrollment.
- •Women who are breast feeding, pregnant, or planning to become pregnant, or are unwilling to apply an effective birth control method (such as implants, injectables, combined oral contraceptives, some intrauterine devices [IUDs], sexual abstinence or vasectomized partner) up to four weeks after the last IMP infusion.
- •Subjects who are accommodated in an institution or care facility based on an official directive or court order.
- •Subjects who are in any way dependent on the Sponsor, Investigator or Study Site.
- •Subjects who received forbidden medication within the washout period as defined in Section 4.2.2 (Table 3).
研究组 & 干预措施
Placebo
Subjects randomized to placebo will receive 4 infusions of placebo every 4 weeks during the blinded First Period (16 weeks). If confirmed deterioration (deterioration at 2 consecutive visits) during the First Period, subjects will be switched to Octagam 10%. After response assessment at Week 16, all subjects with no confirmed deterioration and subjects switched to Octagam 10% due to confirmed deterioration but without further confirmed deterioration during the First Period will continue to receive 2.0 g/kg of Octagam 10% every 4 weeks during the subsequent 6-months open-label Extension Period. At Week 28, subjects who are stable on 2.0 g/kg Octagam 10% can be switched to 1.0 g/kg Octagam 10%, at the discretion of the investigator. Subjects randomized to placebo and switched to Octagam 10% due to confirmed deterioration, who deteriorate also during Octagam 10% treatment at 2 consecutive visits will drop-out after response assessment at Week 16 and will not enter the Extension Period.
干预措施: Placebo (Other)
Octagam10%
Subjects randomized to Octagam will receive 4 infusions of 2.0 g/kg Octagam 10% every 4 weeks during the blinded First Period (16 weeks). If confirmed deterioration (deterioration at 2 consecutive visits) during the First Period, subjects will be switched to the alternate treatment. After response assessment at Week 16, all subjects with no confirmed deterioration during the First Period will continue receiving 2.0 g/kg of Octagam 10% every 4 weeks during the subsequent 6-months open-label Extension Period. At Week 28, subjects who are stable on 2.0 g/kg Octagam 10% can be switched to 1.0 g/kg Octagam 10%, at the discretion of the investigator. Subjects randomized to Octagam and switched to the alternate treatment due to confirmed deterioration will drop-out after response assessment at Week 16 and will not enter the Extension Period.
干预措施: Octagam 10% (Drug)
结局指标
主要结局
Measure the Number of Patients Who Had an Increase of ≥20 Points on the Total Improvement Score (TIS)
时间窗: At week 16
Proportion of responders in the 2.0 g/kg Octagam 10% and placebo arms at Week 16 relative to baseline (Week 0). A responder being defined as a patient with an increase of ≥20 points on the Total Improvement Score (TIS, a scale from 0 to 100; 20-39 points being minimal improvement, 40-59 points being moderate improvement, and ≥60 points being major improvement
次要结局
- Mean Change From Baseline (Week 0) to End of First Period (Week 16) in the Modified Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI)(First 16 weeks)
- Mean Change From Baseline (Week 0) to End of First Period (Week 16) and Extension Period (Week 40) in: Patient Global Disease Activity(From start of the trial till Week 40)
- Mean Change From Baseline (Week 0) to End of First Period (Week 16) and Extension Period (Week 40) in Enzymes (Alanine Aminotransferase)(From start of the trial till Week 40)
- Mean Change From Baseline (Week 0) to End of First Period (Week 16) and Extension Period (Week 40) in Enzymes (Aldolase)(From start of the trial till Week 40)
- Proportion of TIS Responders by Improvement Category at Week 40(40 weeks)
- Mean Change From Baseline (Week 0) to End of Extension Period (Week 40) in the Modified Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI)(40 weeks)
- Mean Change From Baseline (Week 0) to End of First Period (Week 16) and Extension Period (Week 40) in Enzymes (Creatine Kinase)(From start of the trial till Week 40)
- Time to Confirmed Deterioration in the First Period and Overall(Up to 40 weeks)
- Mean Change From Baseline (Week 0) to End of First Period (Week 16) and Extension Period (Week 40) in: SF-36v2 Health Survey(From start of the trial till Week 40)
- Mean Change From Baseline (Week 0) to End of First Period (Week 16) and Extension Period (Week 40) in: MMT-8(From start of the trial till Week 40)
- Time to Minimal, Moderate and Major Improvement in TIS(Up to 40 weeks)
- Proportion of TIS Responders by Improvement Category at Week 16(16 weeks)
- Mean Change From Baseline (Week 0) to End of First Period (Week 16) and Extension Period (Week 40) in: Health Assessment Questionnaire(From start of the trial till Week 40)
- Mean Change From Baseline (Week 0) to End of First Period (Week 16) and Extension Period (Week 40) in Enzymes (Lactate Dehydrogenase)(From start of the trial till Week 40)
- Mean TIS From Baseline (Week 0) to End of First Period (Week 16) and From Baseline (Week 0) to End of Extension Period (Week 40)(Up to 40 weeks)
- Mean Change From End of First Period (Week 16) to End of Extension Period (Week 40) in the Modified Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI)(From week 16 to Week 40)
- Mean Change From Baseline (Week 0) to End of First Period (Week 16) and Extension Period (Week 40) in Physician's Global Disease Activity(From start of the trial till Week 40)
- Mean Change From Baseline (Week 0) to End of First Period (Week 16) and Extension Period (Week 40) in Enzymes (Aspartate Aminotransferase)(From start of the trial till Week 40)
- Mean Change From Baseline (Week 0) to End of First Period (Week 16) and Extension Period (Week 40) in: Extra-muscular Activity(From start of the trial until Week 40)