Prospective, Double-blind, Randomized, Multicenter Phase III Study Evaluating Efficacy and Safety of Three Different Dosages of NewGam in Patients With Chronic Inflammatory Demyelinating Poly(Radiculo)Neuropathy
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Octapharma
- 入组人数
- 142
- 试验地点
- 26
- 主要终点
- Decrease in the Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Score
研究概览
简要总结
Study to evaluate the Efficacy and Safety of Three Different Dosages of NewGam in Patients With Chronic Inflammatory Demyelinating Poly(radiculo)neuropathy
详细描述
Prospective, Double-blind, Randomized, Multicenter Phase III Study Evaluating Efficacy and Safety of Three Different Dosages of NewGam in Patients With Chronic Inflammatory Demyelinating Poly(radiculo)neuropathy ("ProCID trial")
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with diagnosis of definite or probable Chronic inflammatory demyelinating polyneuropathy (CIDP) according to the European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) Guideline 2010 [van den Bergh et al., 2010]; including patients with Multifocal Acquired Demyelinating Sensory And Motor Neuropathy (MADSAM) or pure motor Chronic inflammatory demyelinating polyneuropathy (CIDP )
- •Patients currently depending on treatment with immunoglobulins or corticosteroids
- •Patients with active disease, i.e. not being in remission, who are progressive or relapsing prior to trial start or during the Wash-out Phase
- •Weakness of at least 2 limbs
- •>18 to <80 years of age
- •Adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability score between 2 and 9 (with a score of 2 coming exclusively from leg disability)
- •Voluntarily given, fully informed written consent obtained from patient before any study-related procedures are conducted
排除标准
- •Unifocal forms of Chronic inflammatory demyelinating polyneuropathy (CIDP)
- •Pure sensory Chronic inflammatory demyelinating polyneuropathy (CIDP)
- •Multifocal motor neuropathy (MMN) with conduction block [van den Bergh et al., 2010]
- •Patients who previously failed immunoglobulin treatment
- •Treatment with immunomodulatory/suppressive agents (cyclosporin, methotrexate, mitoxantrone, mycophenolate mofetil or azathioprine) during the six months prior to baseline visit
- •Patients on or treated with rituximab, alemtuzumab, cyclophosphamide, or other intensive chemotherapeutic regimens, previous lymphoid irradiation or stem cell transplantation during the 12 months prior to baseline visit
- •Respiratory impairment requiring mechanical ventilation
- •Myelopathy or evidence of central nervous system demyelination or significant persisting neurological deficits from stroke, or central nervous system (CNS) trauma
- •Clinical evidence of peripheral neuropathy from another cause such as
- •connective tissue disease or systemic lupus erythematosus (SLE)
- •HIV infection, hepatitis, Lyme disease
- •cancer (with the exception of basal cell skin cancer)
- •IgM paraproteinemia with anti-myelin associated glycoprotein antibodies
- •Diabetic neuropathy
- •Cardiac insufficiency (New York Heart Association [NYHA] III/IV), cardiomyopathy, significant cardiac dysrhythmia requiring treatment, unstable or advanced ischemic heart disease
- •Severe liver disease (ALAT 3x > normal value)
- •Severe kidney disease (creatinine 1.5x > normal value)
- •Hepatitis B, hepatitis C or HIV infection
- •Thromboembolic events: patients with a history of deep vein thrombosis (DVT) within the last year prior to baseline visit or pulmonary embolism ever; patients with susceptibility to embolism or deep vein thrombosis (DVT)
- •Body mass index (BMI) ≥40 kg/m2
- •Patients with uncompensated hypothyroidism (abnormally high Thyroid-Stimulating Hormone [TSH] and abnormally low Thyroxine [T4]) or known vitamin B12 deficiency if patients don't receive adequate substitution therapy
- •Medical conditions whose symptoms and effects could alter protein catabolism and/or Immunoglobulin G (IgG) utilization (e.g. protein-losing enteropathies, nephrotic syndrome)
- •Known Immunoglobulin A (IgA) deficiency with antibodies to Immunoglobulin A (IgA)
- •History of severe hypersensitivity, e.g. anaphylaxis or severe systemic response to immuno-globulin, blood or plasma derived products, or any component of NewGam
- •Known blood hyperviscosity, or other hypercoagulable states
- •Use of other blood or plasma-derived products within three months prior to Visit 2
- •Patients with a past or present history of drug abuse or alcohol abuse within the preceding five years prior to baseline visit
- •Patients unable or unwilling to understand or comply with the study protocol
- •Participation in another interventional clinical study with investigational medicinal product (IMP) treatment currently or during the three months prior to Visit 2
- •Women who are breast feeding, pregnant, or planning to become pregnant, or are unwilling to use an effective birth control method (such as implants, injectables, combined oral contraceptives, some intrauterine devices (IUDs), sexual abstinence or vasectomized partner) while on study
研究组 & 干预措施
0.5 g/kg NewGam
All patients will receive a loading dose of 2.0 g/kg Newgam (administered over two consecutive days), followed by seven infusions of the maintenance dose the patient has been randomized to (0.5g/kg NewGam), also administered over two consecutive days every 3 weeks (±4 days).
干预措施: NewGam (Drug)
1.0 g/kg NewGam
All patients will receive a loading dose of 2.0 g/kg Newgam (administered over two consecutive days), followed by seven infusions of the maintenance dose the patient has been randomized to (1.0g/kg NewGam), also administered over two consecutive days every 3 weeks (±4 days).
干预措施: NewGam (Drug)
2.0 g/kg NewGam
All patients will receive a loading dose of 2.0 g/kg Newgam (administered over two consecutive days), followed by seven infusions of the maintenance dose the patient has been randomized to (2.0g/kg NewGam), also administered over two consecutive days every 3 weeks (±4 days).
干预措施: NewGam (Drug)
结局指标
主要结局
Decrease in the Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Score
时间窗: at Week 24
Efficacy - Proportion of responders in the 1.0 g/kg NewGam arm at Week 24 (Termination Visit) relative to baseline (Week 0). A responder being defined as a patient with a decrease of at least 1 point on the adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability score (a scale from 0 to 10, from healthy to unable to make any purposeful movements with arms and/or legs)
次要结局
- Decrease in the Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Score(at Week 24)
- Grip Strength Score(at Week 24)
- Inflammatory Rasch-built Overall Disability Scale (I-RODS Score)(at Week 24)
- Worsening in the Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Score(Week 24)
- Mean Change in Grip Strength(Up to 24 weeks)
- Inflammatory Rasch-built Overall Disability Scale (I-RODS)(Up to 24 weeks)
- Motor Nerves(Up to 24 weeks)
- Mean Change in Pain Intensity Numerical Rating Scale (PI-NRS Scale)(Up to 24 weeks)
- Worsening on the Inflammatory Rasch-built Overall Disability Scale (I-RODS Scale)(24 weeks)
- 1 Point Decrease in the INCAT Disability Score(24 weeks)
- Decrease in Inflammatory Rasch-built Overall Disability Scale (I-RODS Scale)(24 weeks)