Study in Subjects With Light Chain (AL) Amyloidosis

NCT ID: NCT03154047

Last Updated: 2019-03-26

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-06-14
• Study Completion Date: 2018-05-30

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).

Conditions

AL Amyloidosis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Open label

Open Label Study Drug NEOD001

Group Type: EXPERIMENTAL

NEOD001

Intervention Type: DRUG

humanized monoclonal antibody

Interventions

NEOD001

humanized monoclonal antibody

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Prothena Biosciences Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

City of Hope

Duarte, California, United States

Colorado Blood Cancer Institute

Denver, Colorado, United States

Mayo Clinic Hospital - Florida

Jacksonville, Florida, United States

University of Chicago Medicine

Chicago, Illinois, United States

Indiana University Simon Cancer Center

Indianapolis, Indiana, United States

Tufts Medical Center

Boston, Massachusetts, United States

Karmanos Cancer Institute

Detroit, Michigan, United States

Mayo Clinic - Minnesota

Rochester, Minnesota, United States

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Duke University Medical Center

Durham, North Carolina, United States

Cleveland Clinic

Cleveland, Ohio, United States

Oregon Health & Science University

Portland, Oregon, United States

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Westmead Hospital

Sydney, New South Wales, Australia

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

Eastern Health (Box Hill Hospital)

Box Hill, Victoria, Australia

Medizinische Universität Wien

Vienna, , Austria

Hôpital Dupuytren - CHU Limoges

Limoges, , France

Hôpital Pitié-Salpêtrière

Paris, , France

Charité - Universitätsmedizin Berlin

Berlin, , Germany

University of Duisburg-Essen

Essen, , Germany

Universitätsklinikum Hamburg-Eppendorf (UKE)

Hamburg, , Germany

Universitätsklinikum Heidelberg

Heidelberg, , Germany

Alexandra General Hospital of Athens

Athens, , Greece

University Hospital of Patras

Pátrai, , Greece

Hadassah Medical Center (HMC)

Jerusalem, , Israel

Fondazione IRCCS Policlinico San Matteo

Pavia, , Italy

Hospital Clínic de Barcelona

Barcelona, , Spain

Hospital Universitario Puerta de Hierro - Majadahonda

Majadahonda, , Spain

Queen Elizabeth Hospital

Birmingham, England, United Kingdom

The Royal Free Hospital

London, England, United Kingdom

Countries

United States; Australia; Austria; France; Germany; Greece; Israel; Italy; Spain; United Kingdom

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Other Identifiers

NEOD001-OLE251

Identifier Type: -

Identifier Source: org_study_id