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

AL Amyloidosis Clinical Trial

— PRONTO  

Official title:

A Phase 2b, Randomized, Double-blind, Placebo-controlled Study of NEOD001 in Previously Treated Subjects With Light Chain (AL) Amyloidosis Who Have Persistent Cardiac Dysfunction

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02632786
• Other study ID #: NEOD001-201
• Status: Completed
• Phase: Phase 2
• Start date: March 2016
• Est. completion date: March 2018

Study information

• Verified date: April 2019
• Source: Prothena Therapeutics Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 129
• Est. completion date: March 2018
• Est. primary completion date: March 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Age =18 years

2. Confirmed diagnosis of systemic AL amyloidosis

3. =1 prior systemic plasma cell dyscrasia therapy with at least a partial hematologic response

4. Cardiac involvement

5. NT-proBNP =650

Exclusion Criteria:

1. Non-AL amyloidosis

2. Meets the International Myeloma Working Group (IMWG) definition of Multiple Myeloma

3. NT-proBNP >5000

4. Received Plasma cell directed chemotherapy within 6 months

5. Received autologous stem cell transplant (ASCT) within 12 months

Related Conditions & MeSH terms

• AL Amyloidosis
• Amyloidosis
• Immunoglobulin Light-chain Amyloidosis

Intervention

Drug:
• NEOD001
NEOD001 is a monoclonal antibody directed at soluble and insoluble light chain aggregates
• Placebo
Saline Bag

Locations

Country	Name	City	State
Australia	Eastern Health (Box Hill Hospital)	Box Hill	Victoria
Australia	Westmead Hospital	Sydney	New South Wales
Australia	The University of Queensland - Princess Alexandra Hospital (PAH)	Woolloongabba	Queensland
Austria	Medizinische Universität Wien, Allgemeines Krankenhaus der Stadt Wien	Vienna
France	Hôpital Dupuytren - CHU Limoges	Limoges
France	Hôpital Pitié-Salpêtrière	Paris
France	Hopitaux Lyon Sud	Pierre-Benite Cedex
France	CHU Rennes, Service de Medecine Interne	Rennes Cedex 2
Germany	Charite-Universitatsmedizin	Berlin
Germany	Universitätsklinikum Essen	Essen
Germany	Universitatsklinikum Hamburg-Eppendorf (UKE	Hamburg
Germany	Universitatsklinikum Heidelberg	Heidelberg
Greece	Alexandra General Hospital of Athens	Athens
Greece	University Hospital of Patras	Patras
Israel	Hadassah University Medical Center	Jerusalem
Italy	Policlinica San Matteo	Pavia
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital Universitario Puerta de Hierro - Majadahonda	Majadahonda
United Kingdom	Centre for Clinical Haematology	Birmingham
United Kingdom	The Royal Free London NHS Foundation Trust - The Royal Free Hospital	London
United Kingdom	Southampton General Hospital	Southampton
United States	Boston University School of Medicine	Boston	Massachusetts
United States	Tufts Medical Center	Boston	Massachusetts
United States	University of Chicago Medicine	Chicago	Illinois
United States	The Cleveland Clinic	Cleveland	Ohio
United States	Colorado Blood Cancer Institute	Denver	Colorado
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	City of Hope	Duarte	California
United States	Duke University Medical Center	Durham	North Carolina
United States	University of Texas; MD Anderson Cancer Center	Houston	Texas
United States	Indiana University Simon Cancer Center	Indianapolis	Indiana
United States	Mayo Clinic	Jacksonville	Florida
United States	Froedtert & Medical College of Wisconsin, Cancer Center - Froedtert Hospital	Milwaukee	Wisconsin
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Oregon Health & Science University	Portland	Oregon
United States	Mayo Clinic - Minnesota	Rochester	Minnesota
United States	University of Washington/Seattle Cancer Care Alliance	Seattle	Washington
United States	Stanford Cancer Institute (SCI)	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Prothena Therapeutics Ltd.

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	SF-36v2 PCS Score	Change in Short Form-36 (SF-36 version 2) questionnaire Physical Component Summary [PCS] Score. PCS scores are calculated based on responses to specific Short Form-36 (version 2) questions using a weight scoring method. The lower the PCS score the more disability, the higher the score the less disability. A score of 50 is the mean in the US General Population and the standard deviation is 10. Minimum is 0 and maximum value is 100.	Baseline to 12 months of treatment
Secondary	6MWT Distance	Change in 6 Minute Walk Test (6MWT) Distance (meters)	Baseline to 12 months of treatment
Secondary	Number of Participants With Renal Best Response and Non-Response	Proteinuria and estimated Glomerular Filtration Rate (eGFR) response (Response or Non-Response [Stable, Progression]) from baseline through 12 months of treatment in subjects with renal involvement. Renal best response, as assessed by proteinuria, is defined as the most favorable category among response (ie, =30% decrease from baseline or <0.5 g/24 hours postbaseline result if subject does not meet criteria for progression), stable (ie, neither response nor progression), and progression (ie, =25% decrease in eGFR from baseline) 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. Assessments that qualify as both a response and progression are counted as progression.; Non-response is defined as either stable or progression.	Baseline through 12 months of treatment
Secondary	NIS-LL Total Score	Change in Neuropathy Impairment Score-Lower Limb (NIS-LL) Total Score in subjects with peripheral nerve involvement. NIS-LL is a scoring system graduated from 0 points to a maximum of 88 points (the absence of all motor, sensory, and reflex activity in the lower extremities). The scale is an additive of all deficits (64 potential points for muscle strength, 8 points for reflexes, and 16 points for sensory function) in the lower extremities. A score of 0 is normal and score of 88 is total impairment.	Baseline to 12 months of treatment
Secondary	NT-proBNP Slope	Rate of change in NT-proBNP (ng/L per infusion). Estimates of the intercept, slope, SE, and associated 95% CI for each treatment group, and the NEOD001 and placebo group difference comparisons are estimated using a general linear mixed effects model. The model fits a random intercept and slope for each subject and includes fixed effects for treatment group, time, treatment group by time interaction, IWRS stratification factors (hematologic response to first-line therapy: CR/VGPR, PR and NT-proBNP <1800 ng/L, =1800 ng/L), and an unstructured covariance structure to model the within-subject errors. Time is represented in months as a continuous variable and includes all scheduled time points, including baseline. The p-value is associated with the visit by treatment group interaction term.	Baseline through 12 months of treatment
Secondary	Hepatic Best Response	Alkaline Phosphatase response (Response or Non-Response [Stable, Progression]) from baseline through 12 months of treatment in subjects with hepatic involvement	Baseline through 12 months of treatment