Trial Outcomes & Findings for Zoster Eye Disease Study (NCT NCT03134196)

Last Updated: 2025-03-07

Results Overview

The number of participants with the first confirmed endpoint (new or worsening SK, EK, IR, DEK or SKU associated with pre-specified definitions of these disease manifestations and associated treatment requirements within 12 months in study participants assigned to valacyclovir compared to placebo. Diagnostic criteria were defined using the classification for SK, EK, SKU, and DEK caused by Herpes Simplex Virus (HSV) and standardization of uveitis nomenclature (SUN) for IR. A substantial increase in topical steroid treatment, defined as starting, shifting from a lower to higher potency steroid, or doubling frequency of steroid at one visit (new) or gradually within 3 months (worsening) was required for SK, EK, IR, and SKU.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

527 participants

Primary outcome timeframe

Month 12

Results posted on

2025-03-07

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo Encapsulated masked placebo Masked Placebo: Oral Placebo	Masked Oral Valacyclovir 1000 mg Daily Valacyclovir, 500 mg, oral pill, two 500mg pills daily Masked Oral Valacyclovir: Oral Valacyclovir 1000 mg/day
Overall Study STARTED	261	266
Overall Study COMPLETED	223	237
Overall Study NOT COMPLETED	38	29

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Encapsulated masked placebo Masked Placebo: Oral Placebo	Masked Oral Valacyclovir 1000 mg Daily Valacyclovir, 500 mg, oral pill, two 500mg pills daily Masked Oral Valacyclovir: Oral Valacyclovir 1000 mg/day
Overall Study Death	2	1
Overall Study Lost to Follow-up	13	15
Overall Study Physician Decision	0	1
Overall Study Withdrawal by Subject	19	12
Overall Study Site Unable to Contact Participant	2	0
Overall Study Site Closed Scheduling Conflict	1	0
Overall Study Scheduling Conflict	1	0

Baseline Characteristics

Zoster Eye Disease Study

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=261 Participants Encapsulated masked placebo Masked Placebo: Oral Placebo	Masked Oral Valacyclovir 1000 mg Daily n=266 Participants Valacyclovir, 500 mg, oral pill, two 500mg pills daily Masked Oral Valacyclovir: Oral Valacyclovir 1000 mg/day	Total n=527 Participants Total of all reporting groups
Age, Continuous	58 years n=5 Participants	58 years n=7 Participants	58 years n=5 Participants
Sex: Female, Male Female	135 Participants n=5 Participants	131 Participants n=7 Participants	266 Participants n=5 Participants
Sex: Female, Male Male	126 Participants n=5 Participants	135 Participants n=7 Participants	261 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	15 Participants n=5 Participants	11 Participants n=7 Participants	26 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	246 Participants n=5 Participants	255 Participants n=7 Participants	501 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) Asian	13 Participants n=5 Participants	14 Participants n=7 Participants	27 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	15 Participants n=5 Participants	7 Participants n=7 Participants	22 Participants n=5 Participants
Race (NIH/OMB) White	222 Participants n=5 Participants	235 Participants n=7 Participants	457 Participants n=5 Participants
Race (NIH/OMB) More than one race	10 Participants n=5 Participants	6 Participants n=7 Participants	16 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment Canada	29 participants n=5 Participants	34 participants n=7 Participants	63 participants n=5 Participants
Region of Enrollment United States	224 participants n=5 Participants	226 participants n=7 Participants	450 participants n=5 Participants
Region of Enrollment New Zealand	8 participants n=5 Participants	6 participants n=7 Participants	14 participants n=5 Participants

PRIMARY outcome

Timeframe: Month 12

Population: Data were analyzed by intention-to-treat. Treatment requirements for endpoints were revised on January 6, 2020 to allow a recent reduction in steroids for SK, EK, IR, and SKU as the estimated endpoint rate assumed this, and applied retroactively to all endpoints without any knowledge of study outcome data by treatment group.

Outcome measures

Outcome measures
Measure	Placebo n=261 Participants Encapsulated masked placebo Masked Placebo: Oral Placebo	Masked Oral Valacyclovir 1000 mg Daily n=266 Participants Valacyclovir, 500 mg, oral pill, two 500mg pills daily Masked Oral Valacyclovir: Oral Valacyclovir 1000 mg/day
Number of Participants With the First Occurrence of New or Worsening Stromal Keratitis Without Ulceration (SK), Endothelial Keratitis (EK), Iritis (IR), Dendriform Epithelial Keratitis (DEK), or Stromal Keratitis With Ulceration (SKU)	86 Participants	75 Participants

SECONDARY outcome

Timeframe: Month 18 (6 months post treatment)

A secondary endpoint, at 18 months, assessed whether the treatment effect persisted 6 months after treatment. Diagnostic criteria were defined using the classification for SK, EK, SKU, and DEK caused by HSV and standardization of uveitis nomenclature (SUN) for IR. A substantial increase in topical steroid treatment, defined as starting, shifting from a lower to higher potency steroid, or doubling frequency of steroid at one visit (new) or gradually within 3 months (worsening) was required for SK, EK, IR, and SKU.

Outcome measures

Outcome measures
Measure	Placebo n=261 Participants Encapsulated masked placebo Masked Placebo: Oral Placebo	Masked Oral Valacyclovir 1000 mg Daily n=266 Participants Valacyclovir, 500 mg, oral pill, two 500mg pills daily Masked Oral Valacyclovir: Oral Valacyclovir 1000 mg/day
Number of Participants With Persistent Treatment Benefit at 18 Months, 6 Months After Cessation of Treatment	104 Participants	87 Participants

SECONDARY outcome

Timeframe: Month 12

Population: Data were analyzed by intention-to-treat.

PHN was defined by a Zoster Brief Pain Inventory (ZBPI) score of ≥ 3 (the level at which pain interferes with normal activities), persisting, occurring, or reoccurring 3 or more months after the onset of Herpes Zoster Ophthalmicus (HZO).

Outcome measures

Outcome measures
Measure	Placebo n=261 Participants Encapsulated masked placebo Masked Placebo: Oral Placebo	Masked Oral Valacyclovir 1000 mg Daily n=266 Participants Valacyclovir, 500 mg, oral pill, two 500mg pills daily Masked Oral Valacyclovir: Oral Valacyclovir 1000 mg/day
Number of Postherpetic Neuralgia (PHN) Episodes	24 Number of PHN episodes	25 Number of PHN episodes

SECONDARY outcome

Timeframe: Month 18 (6 months post treatment)

Population: Data were analyzed by intention-to-treat.

PHN was defined by a ZBPI score of ≥ 3 (the level at which pain interferes with normal activities), persisting, occurring, or reoccurring 3 or more months after the onset of HZO

Outcome measures

Outcome measures
Measure	Placebo n=261 Participants Encapsulated masked placebo Masked Placebo: Oral Placebo	Masked Oral Valacyclovir 1000 mg Daily n=266 Participants Valacyclovir, 500 mg, oral pill, two 500mg pills daily Masked Oral Valacyclovir: Oral Valacyclovir 1000 mg/day
Number of Postherpetic Neuralgia (PHN) Episodes	20 Number of PHN episodes	16 Number of PHN episodes

SECONDARY outcome

Timeframe: Month 24 (12 months post-treatment)

Population: Data were analyzed by intention-to-treat.

The duration of pain after zoster is obtained at every visit when they reported pain. Outcome measure was obtained using the Zoster Brief Pain Inventory (ZBPI) score of worst pain in last 24 hours of 3/10 (the level at which pain interferes with normal activities) or more occurring 3 or more months after HZO onset was used to determine the prevalence, severity and duration of PHN.

Outcome measures

Outcome measures
Measure	Placebo n=261 Participants Encapsulated masked placebo Masked Placebo: Oral Placebo	Masked Oral Valacyclovir 1000 mg Daily n=266 Participants Valacyclovir, 500 mg, oral pill, two 500mg pills daily Masked Oral Valacyclovir: Oral Valacyclovir 1000 mg/day
Average Duration of Postherpetic Neuralgia (PHN) Pain	14.3 Months Interval 10.8 to 17.8	13.6 Months Interval 10.7 to 16.4

SECONDARY outcome

Timeframe: Month 30 (18 months post treatment)

Population: Data were analyzed by intention-to-treat.

Outcome measures

Outcome measures
Measure	Placebo n=261 Participants Encapsulated masked placebo Masked Placebo: Oral Placebo	Masked Oral Valacyclovir 1000 mg Daily n=266 Participants Valacyclovir, 500 mg, oral pill, two 500mg pills daily Masked Oral Valacyclovir: Oral Valacyclovir 1000 mg/day
Average Duration of Postherpetic Neuralgia (PHN) Pain	18.7 Months Interval 13.6 to 23.7	13.6 Months Interval 11.6 to 15.6

Adverse Events

Placebo

Serious events: 18 serious events

Other events: 0 other events

Deaths: 2 deaths

Masked Oral Valacyclovir 1000 mg Daily

Serious events: 19 serious events

Other events: 0 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Adverse event data not reported

Additional Information

Elisabeth Cohen, MD

NYU Langone Health

Phone: 9294552412

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee No Participating Clinical Center (PCC) investigator is permitted to present or publish data obtained during the conduct of this trial without prior approval from the publications committee. PCC investigators must submit a proposal requesting access to trial data.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=261 participants at risk Encapsulated masked placebo Masked Placebo: Oral Placebo	Masked Oral Valacyclovir 1000 mg Daily n=266 participants at risk Valacyclovir, 500 mg, oral pill, two 500mg pills daily Masked Oral Valacyclovir: Oral Valacyclovir 1000 mg/day
Cardiac disorders Tachy-brady Syndrome	0.38% 1/261 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.	0.00% 0/266 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.
Cardiac disorders Unstable Angina	0.00% 0/261 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.	0.38% 1/266 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.
Cardiac disorders Heart Attack	0.00% 0/261 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.	0.38% 1/266 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.
Cardiac disorders Myocardial Infarction	0.38% 1/261 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.	0.00% 0/266 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.
Cardiac disorders Left Main Coronary Artery Disease	0.38% 1/261 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.	0.00% 0/266 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.
Eye disorders Tractional Retinal Detachment with Vitreous Hemorrhage	0.00% 0/261 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.	0.38% 1/266 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.
Gastrointestinal disorders Severe Gastritis	0.00% 0/261 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.	0.38% 1/266 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.
Gastrointestinal disorders Crohn's Flare	0.00% 0/261 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.	0.75% 2/266 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.
General disorders Chest Pain	0.77% 2/261 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.	0.00% 0/266 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.
General disorders Pelvic Mass Status Post Pelvic Abscess	0.00% 0/261 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.	0.38% 1/266 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.
General disorders Sepsis with multi-organ failure	0.38% 1/261 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.	0.00% 0/266 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.
Hepatobiliary disorders Gallstones	0.00% 0/261 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.	0.38% 1/266 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.
Hepatobiliary disorders Jaundice	0.00% 0/261 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.	0.38% 1/266 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.
Infections and infestations COVID-19 Infection	0.38% 1/261 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.	0.38% 1/266 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.
Infections and infestations Sepsis	0.38% 1/261 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.	0.00% 0/266 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.
Infections and infestations Pneumonia	0.38% 1/261 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.	0.00% 0/266 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.
Infections and infestations Sinus Infection	0.38% 1/261 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.	0.00% 0/266 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.
Infections and infestations Hospitalization for Viral Respiratory Infection	0.00% 0/261 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.	0.38% 1/266 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.
Infections and infestations Hospitalization for Bronchitis	0.00% 0/261 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.	0.38% 1/266 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.
Infections and infestations Pelvic Abscess complicated by Sepsis	0.00% 0/261 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.	0.38% 1/266 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.
Infections and infestations Postoperative Abdominal Infection	0.00% 0/261 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.	0.38% 1/266 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.
Investigations RSV	0.00% 0/261 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.	0.38% 1/266 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.
Metabolism and nutrition disorders Diabetic Ketoacidosis	0.00% 0/261 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.	0.38% 1/266 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.
Musculoskeletal and connective tissue disorders Fracture of L1	0.38% 1/261 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.	0.00% 0/266 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal Cell Carcinoma	0.38% 1/261 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.	0.38% 1/266 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast Cancer	0.77% 2/261 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.	0.00% 0/266 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Mantle Cell Lymphoma	0.00% 0/261 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.	0.38% 1/266 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-small cell Lung Cancer	0.00% 0/261 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.	0.38% 1/266 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic Cancer	0.00% 0/261 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.	0.38% 1/266 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate Cancer	0.38% 1/261 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.	0.38% 1/266 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Sarcoma	0.38% 1/261 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.	0.00% 0/266 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.
Nervous system disorders Intracerebral Hemorrhage	0.38% 1/261 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.	0.00% 0/266 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.
Nervous system disorders Headache (Migraine)	0.00% 0/261 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.	0.38% 1/266 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.
Nervous system disorders Stroke	0.00% 0/261 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.	0.38% 1/266 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.
Nervous system disorders Nerve blockage secondary to arthritis in the back	0.38% 1/261 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.	0.00% 0/266 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.
Renal and urinary disorders Acute Kidney Injury	0.38% 1/261 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.	0.00% 0/266 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.
Renal and urinary disorders CT scan shows renal artery stenosis	0.00% 0/261 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.	0.38% 1/266 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.
Reproductive system and breast disorders Benign Prostatic Hyperplasia	0.38% 1/261 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.	0.00% 0/266 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.
Respiratory, thoracic and mediastinal disorders Chest Pain	0.00% 0/261 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.	0.38% 1/266 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.
Respiratory, thoracic and mediastinal disorders COVID-19 Infection	0.00% 0/261 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.	0.75% 2/266 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.
Respiratory, thoracic and mediastinal disorders Pulmonary Embolism	0.00% 0/261 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.	0.38% 1/266 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.
Surgical and medical procedures Laparoscopic Appendectomy	0.38% 1/261 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.	0.00% 0/266 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.
Surgical and medical procedures Emergency Open Heart Surgery	0.00% 0/261 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.	0.38% 1/266 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.
Surgical and medical procedures Replacement of Ascending Aortic Aneurysm with Prosthesis	0.00% 0/261 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.	0.38% 1/266 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.
Vascular disorders Ruptured aortic aneurysm	0.00% 0/261 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.	0.38% 1/266 • 18 months PI only monitored for SAEs at every follow-up visit. SAEs reviewed by Clinical Monitor.