Phase 1/2, Open Label, Dose Escalation Study of NEOD001 in Subjects With Light Chain (AL) Amyloidosis

A Phase 1/2, Open Label, Dose Escalation Study of Intravenous Administration of Single Agent NEOD001 in Subjects With Light Chain (AL) Amyloidosis

Dose escalation study to determine the maximum tolerated dose of NEOD001 in approximately 30 subjects with AL amyloidosis. Expansion phase to evaluate safety, efficacy and pharmacokinetics of NEOD001 in 25 additional subjects at the maximum tolerated dose.

Study Overview

• Status: Completed
• Conditions: Primary Amyloidosis
• Intervention / Treatment: Drug: NEOD001

Detailed Description

The purpose of the dose escalation phase of the study is to determine the maximum tolerated dose/Phase 2 recommended dose of NEOD001 when given as a single agent intravenously in approximately 30 subjects with AL amyloidosis.

The purpose of the expansion phase of the study is to evaluate the safety, preliminary efficacy and pharmacokinetics of single agent NEOD001 at the maximum tolerated dose/Phase 2 recommended dose in approximately 25 additional evaluable subjects.

• Study Type: Interventional
• Enrollment (Actual): 69
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94305
      • Stanford University Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
    • Boston, Massachusetts, United States, 02118
      • Boston University School of Medicine
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan-Kettering Cancer Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania

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. Males and females aged ≥18 years;
2. ECOG performance status (PS) 0-2;
3. Diagnosis of systemic AL amyloidosis (subjects with non-AL amyloidosis are not eligible);
4. Received at least one prior systemic therapy, which may include stem cell transplant, for AL amyloidosis;
5. Have adequate organ function;
6. Ability to understand and willingness to sign informed consent prior to initiation of any study procedures.

Exclusion Criteria:

1. Secondary or familial amyloidosis;
2. Life expectancy of < 3 months;
3. Symptomatic multiple myeloma;
4. Hypersensitivities to other monoclonal antibodies;
5. Known HIV infection;
6. Women who are lactating;
7. Any other condition or prior therapy, which in the opinion of the PI, would make the subject unsuitable for the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Interventional Model: SEQUENTIAL
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: NEOD001; NEOD001 will be administered intravenously once every 28 days. The starting dose will be 0.5 mg/kg. Dose escalation will continue until the the maximum tolerated dose is determined for single agent NEOD001. Approximately 20 additional subjects will be treated with the maximum tolerated dose.	Drug: NEOD001; Monoclonal antibody administered by intravenous infusion every 28 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability	Adverse event profile; Dose limiting toxicity and maximum tolerated dose	28 day cycles, up to 1 year; beyond 1 year with approval of Sponsor and Investigator
Maximum tolerated dose	Adverse event profile; Dose Limiting Toxicity and maximum tolerated dose	28 day cycles, up to 1 year; beyond 1 year with approval of Sponsor and Investigator

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics	• Pharmacokinetic parameters including Cmax, Tmax, AUC, Cav, Cmin, t½, CL, and Vz	28 day cycles, up to 1 year; beyond 1 year with approval of Sponsor and Investigator
Immunogenicity	• Measurement of anti-NEOD001 antibodies	28 day cycles, up to 1 year; beyond 1 year with approval of Sponsor and Investigator

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hematologic Response	• Hematologic response	28 day cycles, up to 1 year; beyond 1 year with approval of Sponsor and Investigator
Organ response	Organ response; Changes in organ function markers	28 day cycles, up to 1 year; beyond 1 year with approval of Sponsor and Investigator

Collaborators and Investigators

• Sponsor: Prothena Biosciences Ltd.
• Investigators: Study Director: Julia Martinisi, Prothena Biosciences Ltd.

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 1, 2013
• Primary Completion (ACTUAL): August 9, 2016
• Study Completion (ACTUAL): August 9, 2016

Study Registration Dates

• First Submitted: October 11, 2012
• First Submitted That Met QC Criteria: October 12, 2012
• First Posted (ESTIMATE): October 16, 2012

Study Record Updates

• Last Update Posted (ACTUAL): August 28, 2018
• Last Update Submitted That Met QC Criteria: August 24, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: AL amyloidosis; Primary amyloidosis
• 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: NEOD001-001