Trial Outcomes & Findings for The PRONTO Study, a Global Phase 2b Study of NEOD001 in Previously Treated Subjects With Light Chain (AL) Amyloidosis (NCT NCT02632786)

Last Updated: 2019-04-05

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

129 participants

Primary outcome timeframe

Baseline through 12 months of treatment

Results posted on

2019-04-05

Participant Flow

Participant milestones

Participant milestones
Measure	NEOD001 24mg/kg NEOD001, 24 mg/kg IV every 4 weeks for 12 months	Placebo Placebo, 0.9% Saline IV every 4 weeks for 12 months
Overall Study STARTED	66	63
Overall Study Informed Consent Obtained	66	63
Overall Study Randomized and Dosed	66	63
Overall Study COMPLETED	55	56
Overall Study NOT COMPLETED	11	7

Reasons for withdrawal

Reasons for withdrawal
Measure	NEOD001 24mg/kg NEOD001, 24 mg/kg IV every 4 weeks for 12 months	Placebo Placebo, 0.9% Saline IV every 4 weeks for 12 months
Overall Study Adverse Event	2	1
Overall Study Death	3	2
Overall Study Physician Decision	5	4
Overall Study Withdrawal by Subject	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	NEOD001 24mg/kg n=66 Participants NEOD001, 24 mg/kg IV every 4 weeks for 12 months	Placebo n=63 Participants Placebo, 0.9% Saline IV every 4 weeks for 12 months	Total n=129 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	41 Participants n=5 Participants	29 Participants n=7 Participants	70 Participants n=5 Participants
Age, Categorical >=65 years	25 Participants n=5 Participants	34 Participants n=7 Participants	59 Participants n=5 Participants
Age, Continuous	62.09 years STANDARD_DEVIATION 9.188 • n=5 Participants	63.90 years STANDARD_DEVIATION 8.332 • n=7 Participants	62.98 years STANDARD_DEVIATION 8.794 • n=5 Participants
Sex: Female, Male Female	27 Participants n=5 Participants	24 Participants n=7 Participants	51 Participants n=5 Participants
Sex: Female, Male Male	39 Participants n=5 Participants	39 Participants n=7 Participants	78 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	64 Participants n=5 Participants	61 Participants n=7 Participants	125 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized Race · American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Race · Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Race · Black or African American	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Race/Ethnicity, Customized Race · White	61 Participants n=5 Participants	56 Participants n=7 Participants	117 Participants n=5 Participants
Race/Ethnicity, Customized Race · Other	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized Race · Multiple Races Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Race · Not reported	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Race · Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline through 12 months of treatment

Population: ITT population

Outcome measures

Outcome measures
Measure	NEOD001 24mg/kg n=66 Participants NEOD001, 24 mg/kg IV every 4 weeks for 12 months	Placebo n=63 Participants Placebo, 0.9% Saline IV every 4 weeks for 12 months
Number of Participants With Cardiac Response and Non-Response Non-response	40 Participants	33 Participants
Number of Participants With Cardiac Response and Non-Response Response	26 Participants	30 Participants

SECONDARY outcome

Timeframe: Baseline to 12 months of treatment

Population: ITT population

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.

Outcome measures

Outcome measures
Measure	NEOD001 24mg/kg n=66 Participants NEOD001, 24 mg/kg IV every 4 weeks for 12 months	Placebo n=63 Participants Placebo, 0.9% Saline IV every 4 weeks for 12 months
SF-36v2 PCS Score	0.19 score on a scale Interval -1.83 to 2.22	0.97 score on a scale Interval -0.99 to 2.93

SECONDARY outcome

Timeframe: Baseline to 12 months of treatment

Population: ITT Population

Change in 6 Minute Walk Test (6MWT) Distance (meters)

Outcome measures

Outcome measures
Measure	NEOD001 24mg/kg n=66 Participants NEOD001, 24 mg/kg IV every 4 weeks for 12 months	Placebo n=63 Participants Placebo, 0.9% Saline IV every 4 weeks for 12 months
6MWT Distance	19.25 meters Interval -21.75 to 59.37	8.00 meters Interval -24.99 to 47.24

SECONDARY outcome

Timeframe: Baseline through 12 months of treatment

Population: Renal Evaluable Population

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.

Outcome measures

Outcome measures
Measure	NEOD001 24mg/kg n=13 Participants NEOD001, 24 mg/kg IV every 4 weeks for 12 months	Placebo n=18 Participants Placebo, 0.9% Saline IV every 4 weeks for 12 months
Number of Participants With Renal Best Response and Non-Response Response	7 Participants	6 Participants
Number of Participants With Renal Best Response and Non-Response Non-Response (Stable, Progression)	6 Participants	12 Participants

SECONDARY outcome

Timeframe: Baseline to 12 months of treatment

Population: Peripheral Neuropathy Evaluable Population

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.

Outcome measures

Outcome measures
Measure	NEOD001 24mg/kg n=12 Participants NEOD001, 24 mg/kg IV every 4 weeks for 12 months	Placebo n=14 Participants Placebo, 0.9% Saline IV every 4 weeks for 12 months
NIS-LL Total Score	-1.2 score on a scale Interval -3.9 to 1.6	-0.6 score on a scale Interval -3.0 to 1.8

SECONDARY outcome

Timeframe: Baseline through 12 months of treatment

Population: ITT population

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.

Outcome measures

Outcome measures
Measure	NEOD001 24mg/kg n=66 Participants NEOD001, 24 mg/kg IV every 4 weeks for 12 months	Placebo n=63 Participants Placebo, 0.9% Saline IV every 4 weeks for 12 months
NT-proBNP Slope	9.45 ng/L per infusion Interval -45.66 to 64.55	81.41 ng/L per infusion Interval 25.15 to 137.68

SECONDARY outcome

Timeframe: Baseline through 12 months of treatment

Population: Hepatic Evaluable Population

Alkaline Phosphatase response (Response or Non-Response \[Stable, Progression\]) from baseline through 12 months of treatment in subjects with hepatic involvement

Outcome measures

Outcome measures
Measure	NEOD001 24mg/kg n=5 Participants NEOD001, 24 mg/kg IV every 4 weeks for 12 months	Placebo n=4 Participants Placebo, 0.9% Saline IV every 4 weeks for 12 months
Hepatic Best Response Response	1 Participants	0 Participants
Hepatic Best Response Non-response	4 Participants	4 Participants

Adverse Events

NEOD001 24 mg/kg

Serious events: 14 serious events

Other events: 58 other events

Deaths: 3 deaths

Placebo

Serious events: 15 serious events

Other events: 52 other events

Deaths: 6 deaths

Serious adverse events

Other adverse events

Additional Information

Wendy Curlin

Prothena

Phone: 650 837 8550

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The PI, institution and the sponsor have agreed that the PI and institution may publish or disclose study results from their site after the earlier of (a) publication of the complete multicenter study results or (b) 18 months after database lock for the multicenter study. The sponsor has at least 45 days to review a proposed publication and may request deletion of confidential information and up to 60 days additional delay to obtain patent protection.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	NEOD001 24 mg/kg n=66 participants at risk 24 mg/kg IV every 4 weeks for 12 months	Placebo n=63 participants at risk 0.9% Saline IV every 4 weeks for 12 months
Infections and infestations Bacteraemia	1.5% 1/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	0.00% 0/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
Infections and infestations Bronchitis	1.5% 1/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	0.00% 0/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
Infections and infestations Localised infection	0.00% 0/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	1.6% 1/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
Infections and infestations Lower respiratory tract infection	0.00% 0/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	1.6% 1/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
Infections and infestations Respiratory tract infection	1.5% 1/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	0.00% 0/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
Infections and infestations Sepsis	1.5% 1/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	0.00% 0/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
Infections and infestations Upper respiratory tract infection	0.00% 0/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	1.6% 1/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
General disorders Pyrexia	0.00% 0/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	3.2% 2/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
General disorders Asthenia	0.00% 0/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	1.6% 1/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
General disorders Oedema peripheral	0.00% 0/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	1.6% 1/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
General disorders Sudden cardiac death	0.00% 0/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	1.6% 1/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
Cardiac disorders Cardiac arrest	1.5% 1/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	0.00% 0/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
Cardiac disorders Cardiac failure acute	0.00% 0/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	1.6% 1/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
Cardiac disorders Cardiac failure congestive	0.00% 0/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	1.6% 1/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
Cardiac disorders Pericardial effusion	1.5% 1/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	0.00% 0/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
Infections and infestations Pneumonia	0.00% 0/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	6.3% 4/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
Infections and infestations Cellulitis	3.0% 2/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	1.6% 1/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
Cardiac disorders Cardiac failure	0.00% 0/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	4.8% 3/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
Cardiac disorders Atrial fibrillation	3.0% 2/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	0.00% 0/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
Cardiac disorders Bradycardia	3.0% 2/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	0.00% 0/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
Cardiac disorders Acute coronary syndrome	0.00% 0/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	1.6% 1/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
Cardiac disorders Angina pectoris	1.5% 1/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	0.00% 0/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
Cardiac disorders Atrioventricular block complete	1.5% 1/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	0.00% 0/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
General disorders Sudden death	0.00% 0/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	1.6% 1/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
Renal and urinary disorders Acute kidney injury	1.5% 1/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	4.8% 3/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
Renal and urinary disorders Ureteric obstruction	1.5% 1/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	0.00% 0/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
Respiratory, thoracic and mediastinal disorders Dyspnoea	3.0% 2/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	1.6% 1/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
Respiratory, thoracic and mediastinal disorders Pleural effusion	3.0% 2/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	1.6% 1/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
Respiratory, thoracic and mediastinal disorders Respiratory failure	1.5% 1/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	0.00% 0/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
Nervous system disorders Syncope	3.0% 2/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	0.00% 0/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
Nervous system disorders Encephalopathy	0.00% 0/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	1.6% 1/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
Nervous system disorders Transient ischaemic attack	1.5% 1/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	0.00% 0/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
Gastrointestinal disorders Abdominal distension	0.00% 0/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	1.6% 1/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
Gastrointestinal disorders Ascites	0.00% 0/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	1.6% 1/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
Gastrointestinal disorders Gastritis	1.5% 1/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	0.00% 0/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
Gastrointestinal disorders Intra-abdominal haemorrhage	0.00% 0/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	1.6% 1/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
Injury, poisoning and procedural complications Fall	0.00% 0/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	1.6% 1/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
Injury, poisoning and procedural complications Laceration	0.00% 0/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	1.6% 1/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
Metabolism and nutrition disorders Fluid overload	1.5% 1/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	1.6% 1/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
Metabolism and nutrition disorders Metabolic syndrome	1.5% 1/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	0.00% 0/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30

Other adverse events
Measure	NEOD001 24 mg/kg n=66 participants at risk 24 mg/kg IV every 4 weeks for 12 months	Placebo n=63 participants at risk 0.9% Saline IV every 4 weeks for 12 months
Infections and infestations Upper respiratory tract infection	9.1% 6/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	12.7% 8/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
Infections and infestations Nasopharyngitis	7.6% 5/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	6.3% 4/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
Infections and infestations Urinary tract infection	9.1% 6/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	4.8% 3/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
Infections and infestations Respiratory tract infection	7.6% 5/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	3.2% 2/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
Infections and infestations Bronchitis	1.5% 1/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	6.3% 4/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
General disorders Fatigue	21.2% 14/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	22.2% 14/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
General disorders Oedema peripheral	10.6% 7/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	12.7% 8/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
General disorders Pyrexia	6.1% 4/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	6.3% 4/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
General disorders Asthenia	6.1% 4/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	0.00% 0/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
Gastrointestinal disorders Diarrhoea	19.7% 13/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	17.5% 11/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
Gastrointestinal disorders Nausea	9.1% 6/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	22.2% 14/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
Gastrointestinal disorders Constipation	10.6% 7/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	9.5% 6/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
Gastrointestinal disorders Vomiting	9.1% 6/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	6.3% 4/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
Gastrointestinal disorders Abdominal distension	4.5% 3/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	6.3% 4/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
Respiratory, thoracic and mediastinal disorders Cough	12.1% 8/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	9.5% 6/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
Respiratory, thoracic and mediastinal disorders Dyspnoea	10.6% 7/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	11.1% 7/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
Respiratory, thoracic and mediastinal disorders Productive cough	6.1% 4/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	3.2% 2/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
Respiratory, thoracic and mediastinal disorders Epistaxis	6.1% 4/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	0.00% 0/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
Musculoskeletal and connective tissue disorders Back pain	7.6% 5/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	6.3% 4/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
Musculoskeletal and connective tissue disorders Muscle spasms	9.1% 6/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	4.8% 3/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
Nervous system disorders Headache	13.6% 9/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	9.5% 6/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
Nervous system disorders Dizziness	7.6% 5/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	12.7% 8/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
Nervous system disorders Hypoaesthesia	7.6% 5/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	3.2% 2/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
Nervous system disorders Paraesthesia	6.1% 4/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	4.8% 3/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
Skin and subcutaneous tissue disorders Rash	3.0% 2/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	7.9% 5/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
Investigations Blood creatinine increased	3.0% 2/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	6.3% 4/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
Investigations Hypocalcaemia	4.5% 3/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	6.3% 4/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
Investigations Hyperuricaemia	0.00% 0/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	6.3% 4/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
Blood and lymphatic system disorders Anaemia	9.1% 6/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	17.5% 11/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
Cardiac disorders Atrial fibrillation	6.1% 4/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	3.2% 2/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
Vascular disorders Hypertension	4.5% 3/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	7.9% 5/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
Vascular disorders Hypotension	3.0% 2/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	6.3% 4/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
Injury, poisoning and procedural complications Contusion	1.5% 1/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	6.3% 4/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30
Renal and urinary disorders Haematuria	7.6% 5/66 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30	3.2% 2/63 • Initiation of study drug through the last study visit or up to 30 days after date of last dose, whichever is later AE that newly appears, increases in frequency, or worsens in severity following initiation of study drug and through the last study visit or up to 30