Study in Subjects With Light Chain (AL) Amyloidosis

Phase 2

Terminated

Conditions: AL Amyloidosis

Interventions: Drug: NEOD001

Registration Number: NCT03154047

Lead Sponsor: Prothena Biosciences Ltd.

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).

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 80

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
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

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.
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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Open label	NEOD001	Open Label Study Drug NEOD001

Primary Outcome Measures

Name	Time	Method
Number of Participants With Adverse Events	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 Outcome Measures

Name	Time	Method

Trial Locations

Locations (34): University of Chicago Medicine
🇺🇸
Chicago, Illinois, United States
Indiana University Simon Cancer Center
🇺🇸
Indianapolis, Indiana, United States
Tufts Medical Center
🇺🇸
Boston, Massachusetts, United States
Cleveland Clinic
🇺🇸
Cleveland, Ohio, United States
The University of Texas MD Anderson Cancer Center
🇺🇸
Houston, Texas, United States
Hadassah Medical Center (HMC)
🇮🇱
Jerusalem, Israel
Princess Alexandra Hospital
🇦🇺
Woolloongabba, Queensland, Australia
Hôpital Dupuytren - CHU Limoges
🇫🇷
Limoges, France
Eastern Health (Box Hill Hospital)
🇦🇺
Box Hill, Victoria, Australia
Universitätsklinikum Hamburg-Eppendorf (UKE)
🇩🇪
Hamburg, Germany
Fondazione IRCCS Policlinico San Matteo
🇮🇹
Pavia, Italy
Charité - Universitätsmedizin Berlin
🇩🇪
Berlin, Germany
Hospital Clínic de Barcelona
🇪🇸
Barcelona, Spain
Hospital Universitario Puerta de Hierro - Majadahonda
🇪🇸
Majadahonda, Spain
University Hospital of Patras
🇬🇷
Patras, Greece
Universitätsklinikum Heidelberg
🇩🇪
Heidelberg, Germany
University of Duisburg-Essen
🇩🇪
Essen, Germany
Vanderbilt University Medical Center
🇺🇸
Nashville, Tennessee, United States
Duke University Medical Center
🇺🇸
Durham, North Carolina, United States
Queen Elizabeth Hospital
🇬🇧
Birmingham, England, United Kingdom
City of Hope
🇺🇸
Duarte, California, United States
Colorado Blood Cancer Institute
🇺🇸
Denver, Colorado, United States
Mayo Clinic Hospital - Florida
🇺🇸
Jacksonville, Florida, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸
New York, New York, United States
Karmanos Cancer Institute
🇺🇸
Detroit, Michigan, United States
Mayo Clinic - Minnesota
🇺🇸
Rochester, Minnesota, United States
Hospital of the University of Pennsylvania
🇺🇸
Philadelphia, Pennsylvania, United States
Oregon Health & Science University
🇺🇸
Portland, Oregon, United States
Westmead Hospital
🇦🇺
Sydney, New South Wales, Australia
Alexandra General Hospital of Athens
🇬🇷
Athens, Greece
Hôpital Pitié-Salpêtrière
🇫🇷
Paris, France
The Royal Free Hospital
🇬🇧
London, England, United Kingdom
Medizinische Universität Wien
🇦🇹
Vienna, Austria
Medical College of Wisconsin
🇺🇸
Milwaukee, Wisconsin, United States