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

Phase 1

Completed

• Conditions: Primary Amyloidosis
• Interventions: Drug: NEOD001

• Registration Number: NCT01707264
• Lead Sponsor: Prothena Biosciences Ltd.

Brief Summary

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.

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 Timeline

• Study First Submitted: 2012-10-11
• Study First Submitted QC: 2012-10-12
• Study First Posted: 2012-10-16
• Study Start: 2013-04
• Primary Completion: 2016-08-09
• Study Completion: 2016-08-09
• Disposition First Submitted: 2017-11-20
• Disposition First Submitted QC: 2017-11-20
• Disposition First Posted: 2017-11-22
• Status Verified: 2018-08
• Last Update Submitted: 2018-08-24
• Last Update Posted: 2018-08-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 69

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
NEOD001	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.

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (7)

Stanford University Cancer Center; 🇺🇸 Palo Alto, California, United States

Memorial Sloan-Kettering Cancer Center; 🇺🇸 New York, New York, United States

Tufts Medical Center; 🇺🇸 Boston, Massachusetts, United States

Boston University School of Medicine; 🇺🇸 Boston, Massachusetts, United States

Karmanos Cancer Institute; 🇺🇸 Detroit, Michigan, United States

Hospital of the University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States