Study in Subjects With Light Chain (AL) Amyloidosis

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)

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.

Study Overview

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

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 Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2145
      • Westmead Hospital
  • Queensland
    • Woolloongabba, Queensland, Australia, 4102
      • Princess Alexandra Hospital
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Eastern Health (Box Hill Hospital)
• Austria
  • Vienna, Austria, 1090
    • Medizinische Universität Wien
• France
  • Limoges, France, 87042
    • Hôpital Dupuytren - CHU Limoges
  • Paris, France, 75651
    • Hopital Pitie-Salpetriere
• Germany
  • Berlin, Germany, 12200
    • Charité - Universitätsmedizin Berlin
  • Essen, Germany, 45122
    • University of Duisburg-Essen
  • Hamburg, Germany, 20246
    • Universitätsklinikum Hamburg-Eppendorf (UKE)
  • Heidelberg, Germany, 69120
    • Universitatsklinikum Heidelberg
• Greece
  • Athens, Greece, 11528
    • Alexandra General Hospital of Athens
  • Patras, Greece
    • University Hospital of Patras
• Israel
  • Jerusalem, Israel, 91120
    • Hadassah Medical Center (HMC)
• Italy
  • Pavia, Italy, 27100
    • Fondazione IRCCS Policlinico San Matteo
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic de Barcelona
  • Majadahonda, Spain, 28222
    • Hospital Universitario Puerta de Hierro - Majadahonda
• United Kingdom
  • England
    • Birmingham, England, United Kingdom, B15 2GW
      • Queen Elizabeth Hospital
    • London, England, United Kingdom, NW3 2QG
      • The Royal Free Hospital
• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope
  • Colorado
    • Denver, Colorado, United States, 80218
      • Colorado Blood Cancer Institute
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Hospital - Florida
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medicine
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Simon Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute
  • Minnesota
    • Rochester, Minnesota, United States, 48201
      • Mayo Clinic - Minnesota
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan-Kettering Cancer Center
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Completed the End of Study Visit in Study NEOD001-201

2. 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
3. Systolic blood pressure 80-180 mmHg
4. 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
5. 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
6. Ability to understand and willingness to sign an informed consent form prior to initiation of any study procedures

Exclusion Criteria:

1. 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
2. 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
3. Myocardial infarction, uncontrolled angina, uncontrolled ventricular arrhythmias, or ECG evidence of acute ischemia, within 6 months prior to the Month 1-Day 1 Visit
4. Severe valvular stenosis (e.g., aortic or mitral stenosis with a valve area <1.0 cm2) or severe congenital heart disease

5. 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])
6. 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.

7. 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

8. 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
9. History of Grade ≥3 infusion-related adverse events (AEs) or hypersensitivity to NEOD001
10. History of severe allergy to any of the components of NEOD001 such as histidine/L-Histidine, Trehalose, or Polysorbate 20
11. Currently known uncontrolled bacterial, viral, fungal, HIV, hepatitis B, or hepatitis C infection
12. Women who are breastfeeding
13. 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
14. Unable or unwilling to adhere to the study-specified procedures and restrictions
15. Subject is under legal custodianship

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Open label; Open Label Study Drug NEOD001	Drug: NEOD001; humanized monoclonal antibody

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events	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.	Each subject's study participation may have been up to 36 months or until the study was terminated

Collaborators and Investigators

• Sponsor: Prothena Biosciences Ltd.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 14, 2017
• Primary Completion (ACTUAL): May 30, 2018
• Study Completion (ACTUAL): May 30, 2018

Study Registration Dates

• First Submitted: April 28, 2017
• First Submitted That Met QC Criteria: May 12, 2017
• First Posted (ACTUAL): May 15, 2017

Study Record Updates

• Last Update Posted (ACTUAL): March 26, 2019
• Last Update Submitted That Met QC Criteria: March 12, 2019
• Last Verified: March 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-OLE251

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No