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)
Overview
- Phase
- Phase 2
- Status
- Terminated
- Sponsor
- Prothena Biosciences Ltd.
- Enrollment
- 80
- Locations
- 34
- Primary Endpoint
- Number of Participants With Adverse Events
Overview
Brief Summary
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.
Detailed Description
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).
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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
Exclusion Criteria
- •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.
Arms & Interventions
Open label
Open Label Study Drug NEOD001
Intervention: NEOD001 (Drug)
Outcomes
Primary Outcomes
Number of Participants With Adverse Events
Time Frame: 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.
Secondary Outcomes
No secondary outcomes reported