A Phase 2b Open-label Extension Study to Evaluate the Long-term Safety and Efficacy of NEOD001 in Subjects With Light Chain (AL) Amyloidosis Who Were Previously Enrolled in Study NEOD001-201 (PRONTO)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 80
- 试验地点
- 34
- 主要终点
- Number of Participants With Adverse Events
研究概览
简要总结
The objective of this study is to evaluate the long-term safety and efficacy of NEOD001 in subjects with AL amyloidosis who have completed Study NEOD001-201.
详细描述
Global, multicenter, Phase 2b, open-label extension study of subjects with AL amyloidosis who had a hematologic response to first-line treatment for their amyloidosis (e.g., chemotherapy, autologous stem cell transplant [ASCT]) and completed Study NEOD001-201. Subjects in this study may receive concomitant chemotherapy. Subject screening will occur during the 28 days prior to the first administration of study drug, which may overlap with the last visit in Study NEOD001-201. If all eligibility requirements are met, the subject will be enrolled and Screening assessments will be completed. Study visits will occur every 28 days based on scheduling from Month 1 Day 1. A ±5-day window is allowed for visits starting after Month 1. Subjects who discontinue study drug before the End of Study Visit (EOS) should have an Early Treatment Discontinuation Visit 30 (±5) days after their final administration of study drug. Each subject's study participation may be up to 38 months or until the study is terminated, whichever occurs first. The study consists of a Screening Phase (1 month), Treatment Phase (36 months), and EOS Visit (30 [±5] days after the last dose).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
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
- •Completed the End of Study Visit in Study NEOD001-201
- •Adequate bone marrow reserve, hepatic and renal function, as demonstrated by:
- •Absolute neutrophil count (ANC) ≥1.0 × 109/L
- •Platelet count ≥75 × 109/L
- •Hemoglobin ≥9 g/dL
- •Total bilirubin ≤2 × upper limit of normal (ULN)
- •Aspartate aminotransferase (AST) ≤3 × ULN
- •Alanine aminotransferase (ALT) ≤3 × ULN
- •Alkaline phosphatase (ALP) ≤5 × ULN (except for subjects with hepatomegaly and isozymes specific to liver, rather than bone)
- •Estimated glomerular filtration rate (eGFR) ≥25 mL/min/1.73 m2 as estimated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, or measured GFR ≥25 mL/min/1.73 m2
- •Systolic blood pressure 80-180 mmHg
- •Women of childbearing potential must have a negative pregnancy test during Screening and must agree to use highly effective physician-approved contraception from Screening to 90 days following the last study drug administration
- •Male subjects must be surgically sterile or must agree to use highly effective physician-approved contraception from Screening to 90 days following the last study drug administration
- •Ability to understand and willingness to sign an informed consent form prior to initiation of any study procedures
排除标准
- •Any new medical contraindication or clinically significant abnormality on physical, neurological, laboratory, vital signs, or electrocardiographic (ECG) examination (e.g., atrial fibrillation; with the exception of subjects for whom the ventricular rate is controlled) that precludes continuation or initiation of treatment with NEOD001 or participation in the study
- •Symptomatic orthostatic hypotension that in the medical judgment of the Investigator would interfere with subject's ability to safely receive treatment or complete study assessments
- •Myocardial infarction, uncontrolled angina, uncontrolled ventricular arrhythmias, or ECG evidence of acute ischemia, within 6 months prior to the Month 1-Day 1 Visit
- •Severe valvular stenosis (e.g., aortic or mitral stenosis with a valve area <1.0 cm2) or severe congenital heart disease
- •ECG evidence of acute ischemia or active conduction system abnormalities with the exception of any of the following:
- •First degree atrioventricular (AV) block
- •Second degree AV block Type 1 (Mobitz Type 1/ Wenckebach type)
- •Right or left bundle branch block
- •Atrial fibrillation with a controlled ventricular rate (uncontrolled [i.e., >110 bpm] ventricular rate is not allowed [determined by an average of three beats in Lead II or 3 representative beats if Lead II is not representative of the overall ECG])
- •Has not recovered (i.e., equivalent to a Common Terminology Criteria for Adverse Events [CTCAE] ≥Grade 2) from the clinically significant toxic effects of prior anticancer therapy. Exception: subjects who have received treatment with a proteasome inhibitor such as bortezomib may have CTCAE Grade 2 neuropathy.
- •Received any of the following within the specified time frame prior to the Month 1-Day 1 Visit:
- •Oral or IV antibiotics, antifungals, or antivirals within 1 week, with the exception of prophylactic oral agents. Note: In the event that a subject requires the chronic use of antivirals, Medical Monitor permission is required for entry into the study.
- •Hematopoietic growth factors, transfusions of blood or blood products within 1 week
- •Chemotherapy, radiotherapy, HDAC inhibitors, or other plasma cell directed therapy within 2 weeks
- •ASCT within 4 weeks (i.e., ASCT is allowed if it occurred before enrollment in Study NEOD001-201 or after completion of Study NEOD001-201 if it was at least 4 weeks before Month 1-Day 1 of this study)
- •Major surgery within 4 weeks (or within 2 weeks following consultation with and approval of Medical Monitor)
- •Planned organ transplant during the study
- •Any investigational agent, other than NEOD001, within 4 weeks
- •Any experimental imaging agent directed at amyloid within 2 weeks
- •Active malignancy with the exception of any of the following:
- •Adequately treated basal cell carcinoma, squamous cell carcinoma, or in situ cervical cancer
- •Adequately treated Stage I cancer from which the subject is currently in remission and has been in remission for ≥2 years
- •Low-risk prostate cancer with Gleason score <7 and prostate-specific antigen <10 mg/mL
- •Any other cancer from which the subject has been disease-free for ≥2 years
- •History of Grade ≥3 infusion-related adverse events (AEs) or hypersensitivity to NEOD001
- •History of severe allergy to any of the components of NEOD001 such as histidine/L-Histidine, Trehalose, or Polysorbate 20
- •Currently known uncontrolled bacterial, viral, fungal, HIV, hepatitis B, or hepatitis C infection
- •Women who are breastfeeding
- •Any condition which could interfere with, or the treatment for which might interfere with, the conduct of the study or which would, in the opinion of the Investigator, unacceptably increase the subject's risk by participating in the study
- •Unable or unwilling to adhere to the study-specified procedures and restrictions
- •Subject is under legal custodianship
研究组 & 干预措施
Open label
Open Label Study Drug NEOD001
干预措施: NEOD001 (Drug)
结局指标
主要结局
Number of Participants With Adverse Events
时间窗: Each subject's study participation may have been up to 36 months or until the study was terminated
AEs are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome, or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards.
次要结局
未报告次要终点