AL AmyloidosisPhase 2PRONTONCT02632786
The PRONTO Study, a Global Phase 2b Study of NEOD001 in Previously Treated Subjects With Light Chain (AL) Amyloidosis
A Phase 2 study testing NEOD001 in people with AL Amyloidosis, run by Prothena Biosciences Ltd. at 40 sites in 10 countries.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- AL Amyloidosis
- What is being tested?
- NEOD001
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 129 participants
- Where
- 40 sitesin 10 countries
- Study dates
- Mar 2016to Mar 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
40 sites in 10 countries.
40 sites in 10 countries
United States19 sites
Tufts Medical Center
Boston, Massachusetts, 02111
Boston University School of Medicine
Boston, Massachusetts, 02118
University of Chicago Medicine
Chicago, Illinois, 60637
The Cleveland Clinic
Cleveland, Ohio, 44195
Colorado Blood Cancer Institute
Denver, Colorado, 80218
Karmanos Cancer Institute
Detroit, Michigan, 48201
City of Hope
Duarte, California, 91010
Duke University Medical Center
Durham, North Carolina, 27705
University of Texas; MD Anderson Cancer Center
Houston, Texas, 77030
Indiana University Simon Cancer Center
Indianapolis, Indiana, 46202
Mayo Clinic
Jacksonville, Florida, 32224
Froedtert & Medical College of Wisconsin, Cancer Center - Froedtert Hospital
Milwaukee, Wisconsin, 53226
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Oregon Health & Science University
Portland, Oregon, 97239
Mayo Clinic - Minnesota
Rochester, Minnesota, 55905
University of Washington/Seattle Cancer Care Alliance
Seattle, Washington, 98109
Stanford Cancer Institute (SCI)
Stanford, California, 94305
France4 sites
Hôpital Dupuytren - CHU Limoges
Limoges, 87042
Hôpital Pitié-Salpêtrière
Paris, 75013
Hopitaux Lyon Sud
Pierre-Bénite, 69495
CHU Rennes, Service de Medecine Interne
Rennes
Germany4 sites
Charite-Universitatsmedizin
Berlin, 12203
Universitätsklinikum Essen
Essen, 45147
Universitatsklinikum Hamburg-Eppendorf (UKE
Hamburg, 20246
Universitatsklinikum Heidelberg
Heidelberg, 69120
Australia3 sites
Eastern Health (Box Hill Hospital)
Box Hill, Victoria, 3128
Westmead Hospital
Sydney, New South Wales, 2145
The University of Queensland - Princess Alexandra Hospital (PAH)
Woolloongabba, Queensland, 4102
United Kingdom3 sites
Centre for Clinical Haematology
Birmingham, B15 2TH
The Royal Free London NHS Foundation Trust - The Royal Free Hospital
London, NW3 2PF
Southampton General Hospital
Southampton
Greece2 sites
Alexandra General Hospital of Athens
Athens, 11528
University Hospital of Patras
Pátrai
Spain2 sites
Hospital Clinic de Barcelona
Barcelona, 08036
Hospital Universitario Puerta de Hierro - Majadahonda
Majadahonda, 28222
Austria1 site
Medizinische Universität Wien, Allgemeines Krankenhaus der Stadt Wien
Vienna
About this study
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
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
- Being tested
- NEOD001, Placebo
- Keywords
- amyloidosis, ntprobnp, NEOD001, Prothena, PRONTO, amyloid, plasma cell dyscrasia, immunotherapy
- Medical subject headings
- Immunoglobulin Light-chain Amyloidosis, Amyloidosis, Alzheimer Disease, Paraproteinemias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NEOD001Drug
NEOD001 is a monoclonal antibody directed at soluble and insoluble light chain aggregates
PlaceboDrug
Saline Bag
| Study group | Role | What they receive |
|---|---|---|
| NEOD001 | Experimental | Study Drug given IV every 28 days at 24mg/kg Receives: Drug: NEOD001 |
| Placebo | Placebo comparator | Placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline through 12 months of treatment
Secondary outcomes (6)
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.
Measured: Baseline to 12 months of treatment
6MWT Distance
Change in 6 Minute Walk Test (6MWT) Distance (meters)
Measured: Baseline to 12 months of treatment
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.
Measured: Baseline through 12 months of treatment
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.
Measured: Baseline to 12 months of treatment
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.
Measured: Baseline through 12 months of treatment
Hepatic Best Response
Alkaline Phosphatase response (Response or Non-Response [Stable, Progression]) from baseline through 12 months of treatment in subjects with hepatic involvement
Measured: Baseline through 12 months of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Dec 2015 (estimated)
- Study startMar 2016
- Primary completionMar 2018
- Study completionMar 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for AL AmyloidosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 129 participants (actual)
Sponsor and investigators
- Lead sponsor
- Prothena Biosciences Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02632786
- Sponsor's protocol ID
- NEOD001-201
- Acronym
- PRONTO
- Status last verified
- Apr 2019
- First submitted
- 9 Dec 2015
- Last updated
- 5 Apr 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 5 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02632786
- Acronym / sponsor ID
- PRONTO / NEOD001-201
- Conditions
- AL Amyloidosis
- Keywords
- amyloidosis, ntprobnp, NEOD001, Prothena, PRONTO, amyloid, plasma cell dyscrasia, immunotherapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 129 participants (actual)
- Lead sponsor
- Prothena Biosciences Ltd.Industry (pharma, biotech, devices)
- Study start
- Mar 2016
- Primary completion
- Mar 2018 (actual)
- Study completion
- Mar 2018 (actual)
- First posted
- 17 Dec 2015 (estimated)
- Results
- Posted 5 Apr 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| NEOD001 | Experimental | Drug: NEOD001Study Drug given IV every 28 days at 24mg/kg |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NEOD001NEOD001 is a monoclonal antibody directed at soluble and insoluble light chain aggregates | Drug | NEOD001 |
| PlaceboSaline Bag | Drug | Placebo |
Primary outcome
Number of Participants With Cardiac Response and Non-Response
Time frame: 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.
6 secondary outcomes
SF-36v2 PCS Score
Time frame: Baseline to 12 months of treatment
6MWT Distance
Time frame: Baseline to 12 months of treatment
Number of Participants With Renal Best Response and Non-Response
Time frame: Baseline through 12 months of treatment
NIS-LL Total Score
Time frame: Baseline to 12 months of treatment
NT-proBNP Slope
Time frame: Baseline through 12 months of treatment
Hepatic Best Response
Time frame: Baseline through 12 months of treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Apr 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Amyloidosis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
40 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing NEOD001 in people with AL Amyloidosis, run by Prothena Biosciences Ltd. at 40 sites in 10 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 40 sites in United States, France, Germany, Australia, United Kingdom and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Apr 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Cardiac Response and Non-Response (time frame: Baseline through 12 months of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Apr 2019.