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

Phase 2

Completed

Conditions: AL Amyloidosis

Interventions: Drug: Placebo
Drug: NEOD001

Registration Number: NCT02632786

Lead Sponsor: Prothena Biosciences Ltd.

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 129

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo
NEOD001	NEOD001	Study Drug given IV every 28 days at 24mg/kg

Primary Outcome Measures

Name	Time	Method
Number of Participants With Cardiac Response and Non-Response	Baseline through 12 months of treatment	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

Name	Time	Method
6MWT Distance	Baseline to 12 months of treatment	Change in 6 Minute Walk Test (6MWT) Distance (meters)
SF-36v2 PCS Score	Baseline to 12 months of treatment	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.
NIS-LL Total Score	Baseline to 12 months of treatment	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	Baseline through 12 months of treatment	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	Baseline through 12 months of treatment	Alkaline Phosphatase response (Response or Non-Response \[Stable, Progression\]) from baseline through 12 months of treatment in subjects with hepatic involvement
Number of Participants With Renal Best Response and Non-Response	Baseline through 12 months of treatment	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.

Trial Locations

Locations (40): City of Hope
🇺🇸
Duarte, California, United States
Stanford Cancer Institute (SCI)
🇺🇸
Stanford, California, United States
Colorado Blood Cancer Institute
🇺🇸
Denver, Colorado, United States
Mayo Clinic
🇺🇸
Jacksonville, Florida, United States
University of Chicago Medicine
🇺🇸
Chicago, Illinois, United States
Indiana University Simon Cancer Center
🇺🇸
Indianapolis, Indiana, 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
Mayo Clinic - Minnesota
🇺🇸
Rochester, Minnesota, United States
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City of Hope
🇺🇸Duarte, California, United States