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

• ClinicalTrials.gov Identifier: NCT01707264
• Recruitment Status: Completed
• First Posted: October 16, 2012
• Last Update Posted: August 28, 2018
• Sponsor: Prothena Biosciences Ltd.
• Information provided by (Responsible Party): Prothena Biosciences Ltd.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Primary Amyloidosis	Drug: NEOD001	Phase 1; Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 69 participants
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1/2, Open Label, Dose Escalation Study of Intravenous Administration of Single Agent NEOD001 in Subjects With Light Chain (AL) Amyloidosis
• Actual Study Start Date: April 2013
• Actual Primary Completion Date: August 9, 2016
• Actual Study Completion Date: August 9, 2016

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Safety and tolerability [ Time Frame: 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
2. Maximum tolerated dose [ Time Frame: 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 :

1. Pharmacokinetics [ Time Frame: 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
2. Immunogenicity [ Time Frame: 28 day cycles, up to 1 year; beyond 1 year with approval of Sponsor and Investigator ]
   • Measurement of anti-NEOD001 antibodies

Other Outcome Measures:

1. Hematologic Response [ Time Frame: 28 day cycles, up to 1 year; beyond 1 year with approval of Sponsor and Investigator ]
   • Hematologic response
2. Organ response [ Time Frame: 28 day cycles, up to 1 year; beyond 1 year with approval of Sponsor and Investigator ]
   • Organ response
   • Changes in organ function markers

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, California

Stanford University Cancer Center

Palo Alto, California, United States, 94305

United States, Massachusetts

Tufts Medical Center

Boston, Massachusetts, United States, 02111

Boston University School of Medicine

Boston, Massachusetts, United States, 02118

United States, Michigan

Karmanos Cancer Institute

Detroit, Michigan, United States, 48201

United States, Minnesota

Mayo Clinic

Rochester, Minnesota, United States, 55905

United States, New York

Memorial Sloan-Kettering Cancer Center

New York, New York, United States, 10065

United States, Pennsylvania

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States, 19104

Sponsors and Collaborators

Prothena Biosciences Ltd.

Investigators

• Study Director: Julia Martinisi; Prothena Biosciences Ltd.

More Information

• Responsible Party: Prothena Biosciences Ltd.
• ClinicalTrials.gov Identifier: NCT01707264
• Other Study ID Numbers: NEOD001-001
• First Posted: October 16, 2012
• Last Update Posted: August 28, 2018
• Last Verified: August 2018

Keywords provided by Prothena Biosciences Ltd.:

AL amyloidosis; Primary amyloidosis

Additional relevant MeSH terms:

Immunoglobulin Light-chain Amyloidosis; Amyloidosis; Proteostasis Deficiencies; Metabolic Diseases; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Paraproteinemias