Open-label Extension Study of NEOD001 in Subjects With Light Chain (AL) Amyloidosis (OLE)

Open-label Extension Study to Evaluate the Long-term Safety and Tolerability of NEOD001 in Subjects With Light Chain (AL) Amyloidosis

The rationale for this study is to provide additional treatment with NEOD001 for subjects who complete Study NEOD001-001, and to continue to evaluate long term safety and tolerability. All subjects in the current NEOD001 trials are being dosed at 24 mg/kg, which will be continued in this study.

Study Overview

• Status: Terminated
• Conditions: AL Amyloidosis
• Intervention / Treatment: Drug: NEOD001

Detailed Description

The rationale for this study is to provide additional treatment with NEOD001 for subjects who complete Study NEOD001-001, and to continue to evaluate long term safety and tolerability. All subjects in the current NEOD001 trials are being dosed at 24 mg/kg, which will be continued in this study. The primary objective of the study is to evaluate long-term safety and tolerability of NEOD001 and the secondary objectives are to assess the immunogenicity of NEOD001 and to incorporate serum NEOD001 concentrations in a population pharmacokinetic (PK) analysis.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford Cancer Institute (SCI)
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Previously enrolled and treated for at least 9 months in Study NEOD001-001
2. Ability to understand and willingness to sign an informed consent form prior to initiation of any study procedures

3. Has 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 times the upper limit of normal (× ULN)
   • Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≤3 × ULN
   • Estimated glomerular filtration rate ≥30 mL/minute
4. Seated systolic blood pressure 90 to 180 mmHg
5. ECOG Performance Status 0 to 2
6. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 28 days prior to the first administration of study drug and agree to use highly effective physician-approved contraception from 30 days prior to the first study drug administration to 90 days following the last study drug administration
7. Male subjects must be surgically sterile or must agree to use highly effective physician-approved contraception from 30 days prior to the first study drug administration to 90 days following the last study drug administration

Exclusion Criteria:

1. Any new medical contraindication or clinically significant abnormality on physical, neurological, laboratory, vital signs, or electrocardiogram (ECG) examination (e.g., atrial fibrillation; with the exception of subjects for whom the ventricular rate is controlled) that precludes continued or initiation of treatment with NEOD001 or participation in the study
2. History of Grade ≥3 infusion-associated adverse events (AEs) or hypersensitivities to NEOD001 or any of its excipients
3. Treatment with any anticancer therapy (standard or investigational) within the 14 days prior to the first dose of study drug. In addition, subjects must have fully recovered (i.e., National Cancer Institute Common Terminology Criteria for Adverse Events [CTCAE] Grade 1 [exception: subjects with prior bortezomib may have CTCAE Grade 2 neuropathy]) from the clinically significant toxic effects of that treatment

4. Received any of the following within the specified time frame prior to the first administration of study drug:

   • Hematopoietic growth factors, transfusions of blood or blood products within 1 week
   • Major surgery within 2 weeks
   • Radiotherapy within 2 weeks
   • Transplant within 8 weeks
   • Investigational drug other than NEOD001 within 4 weeks
   • Another experimental anti-amyloid therapy other than NEOD001 within 2 years
5. Uncontrolled symptomatic orthostatic hypotension
6. Myocardial infarction, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia, within 6 months prior to the first dose of study drug
7. Uncontrolled infection

8. Secondary malignancy, with the exception of:

   • 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
   • Any other cancer from which the subject has been disease-free for ≥3 years
9. Uncontrolled human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infection
10. Women who are lactating

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Open Label; Open Label Study Drug NEOD001	Drug: NEOD001; NEOD001

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Long-term Safety and Tolerability of NEOD001	Adverse events 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.	From initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever came first, assessed up to 24 months

Collaborators and Investigators

• Sponsor: Prothena Biosciences Ltd.

Study record dates

Study Major Dates

• Study Start: February 1, 2016
• Primary Completion (Actual): May 1, 2018
• Study Completion (Actual): May 1, 2018

Study Registration Dates

• First Submitted: November 18, 2015
• First Submitted That Met QC Criteria: November 20, 2015
• First Posted (Estimate): November 24, 2015

Study Record Updates

• Last Update Posted (Actual): May 16, 2019
• Last Update Submitted That Met QC Criteria: May 14, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Paraproteinemias; Proteostasis Deficiencies; Neoplasms, Plasma Cell; Immunoglobulin Light-chain Amyloidosis; Amyloidosis
• Other Study ID Numbers: NEOD001-OLE001