The PRONTO Study, a Global Phase 2b Study of NEOD001 in Previously Treated Subjects With Light Chain (AL) Amyloidosis

NCT02632786 | Completed Phase 2 Results DMC

• 1 other identifier: NEOD001-201
• Study Type: interventional
• Target: 129
• Locations: 9 countries
• Sites: 39

Brief Summary

This is a global, multicenter, Phase 2b, randomized, double-blind, placebo-controlled, two-arm, parallel-group efficacy and safety study of NEOD001 as a single agent administered intravenously in adults with AL amyloidosis who had a hematologic response to previous treatment for their amyloidosis (e.g., chemotherapy, autologous stem cell transplant \[ASCT\]) and have persistent cardiac dysfunction.

Conditions

AL Amyloidosis

Keywords

amyloidosis; ntprobnp; NEOD001; Prothena; PRONTO; amyloid; plasma cell dyscrasia; immunotherapy

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Cardiac Response and Non-Response

  N-terminal pro-brain natriuretic peptide (NT-proBNP ) best response (Response or Non-Response \[Stable, Progression\]) from baseline through 12 months of treatment. Cardiac best response, as assessed by NT-proBNP alone, is defined as the most favorable category among response (ie, decrease in NT-proBNP from baseline of \>30% and \>300 ng/L), stable (ie, neither response nor progression), and progression (ie, increase in NT-proBNP from baseline of \>30% and \>300 ng/L) across all visits after the first infusion of study drug up to and through the end of the study. Subjects are considered non-responders until a response is achieved. Non-response is defined as either stable or progression.

  Baseline through 12 months of treatment

Secondary Outcomes (6)

• SF-36v2 PCS Score

  Baseline to 12 months of treatment

• 6MWT Distance

  Baseline to 12 months of treatment

• Number of Participants With Renal Best Response and Non-Response

  Baseline through 12 months of treatment

• NIS-LL Total Score

  Baseline to 12 months of treatment

• NT-proBNP Slope

  Baseline through 12 months of treatment

Study Arms (2)

NEOD001

EXPERIMENTAL

Study Drug given IV every 28 days at 24mg/kg

Drug: NEOD001

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

NEOD001 DRUG

NEOD001 is a monoclonal antibody directed at soluble and insoluble light chain aggregates

NEOD001

Placebo DRUG

Saline Bag

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years
• Confirmed diagnosis of systemic AL amyloidosis
• ≥1 prior systemic plasma cell dyscrasia therapy with at least a partial hematologic response
• Cardiac involvement
• NT-proBNP ≥650

You may not qualify if:

• Non-AL amyloidosis
• Meets the International Myeloma Working Group (IMWG) definition of Multiple Myeloma
• NT-proBNP \>5000
• Received Plasma cell directed chemotherapy within 6 months
• Received autologous stem cell transplant (ASCT) within 12 months

Sponsors & Collaborators

• Prothena Biosciences Ltd.: lead

Study Sites (40)

City of Hope

Duarte, California, 91010, United States

Location

Stanford Cancer Institute (SCI)

Stanford, California, 94305, United States

Location

Colorado Blood Cancer Institute

Denver, Colorado, 80218, United States

Location

Mayo Clinic

Jacksonville, Florida, 32224, United States

Location

University of Chicago Medicine

Chicago, Illinois, 60637, United States

Location

Indiana University Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Boston University School of Medicine

Boston, Massachusetts, 02118, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Mayo Clinic - Minnesota

Rochester, Minnesota, 55905, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Duke University Medical Center

Durham, North Carolina, 27705, United States

Location

The Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

University of Texas; MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Washington/Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

Froedtert & Medical College of Wisconsin, Cancer Center - Froedtert Hospital

Milwaukee, Wisconsin, 53226, United States

Location

Westmead Hospital

Sydney, New South Wales, 2145, Australia

Location

The University of Queensland - Princess Alexandra Hospital (PAH)

Woolloongabba, Queensland, 4102, Australia

Location

Eastern Health (Box Hill Hospital)

Box Hill, Victoria, 3128, Australia

Location

Medizinische Universität Wien, Allgemeines Krankenhaus der Stadt Wien

Vienna, Austria

Location

Hôpital Dupuytren - CHU Limoges

Limoges, 87042, France

Location

Hôpital Pitié-Salpêtrière

Paris, 75013, France

Location

Hopitaux Lyon Sud

Pierre-Bénite, 69495, France

Location

CHU Rennes, Service de Medecine Interne

Rennes, France

Location

Charite-Universitatsmedizin

Berlin, 12203, Germany

Location

Universitätsklinikum Essen

Essen, 45147, Germany

Location

Universitatsklinikum Hamburg-Eppendorf (UKE

Hamburg, 20246, Germany

Location

Universitatsklinikum Heidelberg

Heidelberg, 69120, Germany

Location

Alexandra General Hospital of Athens

Athens, 11528, Greece

Location

University Hospital of Patras

Pátrai, Greece

Location

Hadassah University Medical Center

Jerusalem, 91120, Israel

Location

Policlinica San Matteo

Pavia, 27100, Italy

Location

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

Location

Hospital Universitario Puerta de Hierro - Majadahonda

Majadahonda, 28222, Spain

Location

Centre for Clinical Haematology

Birmingham, B15 2TH, United Kingdom

Location

The Royal Free London NHS Foundation Trust - The Royal Free Hospital

London, NW3 2PF, United Kingdom

Location

Southampton General Hospital

Southampton, United Kingdom

Location

MeSH Terms

Conditions

Immunoglobulin Light-chain Amyloidosis; Amyloidosis; Alzheimer Disease; Paraproteinemias

Interventions

birtamimab

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases

Results Point of Contact

• Title: Wendy Curlin
• Organization: Prothena

clinicaltrials@prothena.com

650 837 8550

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 9, 2015
• First Posted: December 17, 2015
• Study Start: March 1, 2016
• Primary Completion: March 1, 2018
• Study Completion: March 1, 2018
• Last Updated: April 5, 2019
• Results First Posted: April 5, 2019

Record last verified: 2019-04

Locations

AU (3); GB (3); IL (1); DE (4); IT (1); ES (2); GR (2); US (19); FR (4)