The PRONTO Study, a Global Phase 2b Study of NEOD001 in Previously Treated Subjects With Light Chain (AL) Amyloidosis (PRONTO)
Primary Purpose
AL Amyloidosis
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
NEOD001
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for AL Amyloidosis focused on measuring amyloidosis, ntprobnp, NEOD001, Prothena, PRONTO, amyloid, plasma cell dyscrasia, immunotherapy
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
Sites / Locations
- City of Hope
- Stanford Cancer Institute (SCI)
- Colorado Blood Cancer Institute
- Mayo Clinic
- University of Chicago Medicine
- Indiana University Simon Cancer Center
- Tufts Medical Center
- Boston University School of Medicine
- Karmanos Cancer Institute
- Mayo Clinic - Minnesota
- Memorial Sloan-Kettering Cancer Center
- Duke University Medical Center
- The Cleveland Clinic
- Oregon Health & Science University
- Hospital of the University of Pennsylvania
- Vanderbilt University Medical Center
- University of Texas; MD Anderson Cancer Center
- University of Washington/Seattle Cancer Care Alliance
- Froedtert & Medical College of Wisconsin, Cancer Center - Froedtert Hospital
- Westmead Hospital
- The University of Queensland - Princess Alexandra Hospital (PAH)
- Eastern Health (Box Hill Hospital)
- Medizinische Universität Wien, Allgemeines Krankenhaus der Stadt Wien
- Hôpital Dupuytren - CHU Limoges
- Hôpital Pitié-Salpêtrière
- Hopitaux Lyon Sud
- CHU Rennes, Service de Medecine Interne
- Charite-Universitatsmedizin
- Universitätsklinikum Essen
- Universitatsklinikum Hamburg-Eppendorf (UKE
- Universitatsklinikum Heidelberg
- Alexandra General Hospital of Athens
- University Hospital of Patras
- Hadassah University Medical Center
- Policlinica San Matteo
- Hospital Clinic de Barcelona
- Hospital Universitario Puerta de Hierro - Majadahonda
- Centre for Clinical Haematology
- The Royal Free London NHS Foundation Trust - The Royal Free Hospital
- Southampton General Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
NEOD001
Placebo
Arm Description
Study Drug given IV every 28 days at 24mg/kg
Placebo
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
6MWT Distance
Change in 6 Minute Walk Test (6MWT) Distance (meters)
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.
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.
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.
Hepatic Best Response
Alkaline Phosphatase response (Response or Non-Response [Stable, Progression]) from baseline through 12 months of treatment in subjects with hepatic involvement
Full Information
NCT ID
NCT02632786
First Posted
December 9, 2015
Last Updated
April 2, 2019
Sponsor
Prothena Biosciences Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT02632786
Brief Title
The PRONTO Study, a Global Phase 2b Study of NEOD001 in Previously Treated Subjects With Light Chain (AL) Amyloidosis
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
April 2019
Overall Recruitment Status
Completed
Study Start Date
March 2016 (undefined)
Primary Completion Date
March 2018 (Actual)
Study Completion Date
March 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Prothena Biosciences Ltd.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
AL Amyloidosis
Keywords
amyloidosis, ntprobnp, NEOD001, Prothena, PRONTO, amyloid, plasma cell dyscrasia, immunotherapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
129 (Actual)
8. Arms, Groups, and Interventions
Arm Title
NEOD001
Arm Type
Experimental
Arm Description
Study Drug given IV every 28 days at 24mg/kg
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo
Intervention Type
Drug
Intervention Name(s)
NEOD001
Intervention Description
NEOD001 is a monoclonal antibody directed at soluble and insoluble light chain aggregates
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Saline Bag
Primary Outcome Measure Information:
Title
Number of Participants With Cardiac Response and Non-Response
Description
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.
Time Frame
Baseline through 12 months of treatment
Secondary Outcome Measure Information:
Title
SF-36v2 PCS Score
Description
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.
Time Frame
Baseline to 12 months of treatment
Title
6MWT Distance
Description
Change in 6 Minute Walk Test (6MWT) Distance (meters)
Time Frame
Baseline to 12 months of treatment
Title
Number of Participants With Renal Best Response and Non-Response
Description
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.
Time Frame
Baseline through 12 months of treatment
Title
NIS-LL Total Score
Description
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.
Time Frame
Baseline to 12 months of treatment
Title
NT-proBNP Slope
Description
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.
Time Frame
Baseline through 12 months of treatment
Title
Hepatic Best Response
Description
Alkaline Phosphatase response (Response or Non-Response [Stable, Progression]) from baseline through 12 months of treatment in subjects with hepatic involvement
Time Frame
Baseline through 12 months of treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
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
Facility Information:
Facility Name
City of Hope
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
Stanford Cancer Institute (SCI)
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
Colorado Blood Cancer Institute
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Facility Name
Mayo Clinic
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Facility Name
University of Chicago Medicine
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Indiana University Simon Cancer Center
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Tufts Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02111
Country
United States
Facility Name
Boston University School of Medicine
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02118
Country
United States
Facility Name
Karmanos Cancer Institute
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Mayo Clinic - Minnesota
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Memorial Sloan-Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27705
Country
United States
Facility Name
The Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Oregon Health & Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Hospital of the University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
University of Texas; MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
University of Washington/Seattle Cancer Care Alliance
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Facility Name
Froedtert & Medical College of Wisconsin, Cancer Center - Froedtert Hospital
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Facility Name
Westmead Hospital
City
Sydney
State/Province
New South Wales
ZIP/Postal Code
2145
Country
Australia
Facility Name
The University of Queensland - Princess Alexandra Hospital (PAH)
City
Woolloongabba
State/Province
Queensland
ZIP/Postal Code
4102
Country
Australia
Facility Name
Eastern Health (Box Hill Hospital)
City
Box Hill
State/Province
Victoria
ZIP/Postal Code
3128
Country
Australia
Facility Name
Medizinische Universität Wien, Allgemeines Krankenhaus der Stadt Wien
City
Vienna
Country
Austria
Facility Name
Hôpital Dupuytren - CHU Limoges
City
Limoges
ZIP/Postal Code
87042
Country
France
Facility Name
Hôpital Pitié-Salpêtrière
City
Paris
ZIP/Postal Code
75013
Country
France
Facility Name
Hopitaux Lyon Sud
City
Pierre-Benite Cedex
ZIP/Postal Code
69495
Country
France
Facility Name
CHU Rennes, Service de Medecine Interne
City
Rennes Cedex 2
Country
France
Facility Name
Charite-Universitatsmedizin
City
Berlin
ZIP/Postal Code
12203
Country
Germany
Facility Name
Universitätsklinikum Essen
City
Essen
ZIP/Postal Code
45147
Country
Germany
Facility Name
Universitatsklinikum Hamburg-Eppendorf (UKE
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
Facility Name
Universitatsklinikum Heidelberg
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Facility Name
Alexandra General Hospital of Athens
City
Athens
ZIP/Postal Code
11528
Country
Greece
Facility Name
University Hospital of Patras
City
Patras
Country
Greece
Facility Name
Hadassah University Medical Center
City
Jerusalem
ZIP/Postal Code
91120
Country
Israel
Facility Name
Policlinica San Matteo
City
Pavia
ZIP/Postal Code
27100
Country
Italy
Facility Name
Hospital Clinic de Barcelona
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Facility Name
Hospital Universitario Puerta de Hierro - Majadahonda
City
Majadahonda
ZIP/Postal Code
28222
Country
Spain
Facility Name
Centre for Clinical Haematology
City
Birmingham
ZIP/Postal Code
B15 2TH
Country
United Kingdom
Facility Name
The Royal Free London NHS Foundation Trust - The Royal Free Hospital
City
London
ZIP/Postal Code
NW3 2PF
Country
United Kingdom
Facility Name
Southampton General Hospital
City
Southampton
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
The PRONTO Study, a Global Phase 2b Study of NEOD001 in Previously Treated Subjects With Light Chain (AL) Amyloidosis
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