Safety,Tolerability and Efficacy of Intravitreal LFG316 in Patients With Active Non-infectious Intermediate-, posterior-or Panuveitis ,

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01526889
• Collaborator: (none)
• Enrollment: 25
• Locations: 8
• Arms: 2
• Actual Duration (Months): 56.1
• Patients Per Site: 3.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This was a multi-center, randomized, active-controlled, open-label study. Approximately 24 patients with active, non-infectious intermediate-, posterior-, or panuveitis requiring systemic immunosuppressive therapy were enrolled.

Safety, efficacy, and PK assessments occurred at scheduled visits over a 12-week period. Low-molecular-weight non-steroidal immunosuppressive medications were allowed up to the baseline day as long as the dose had not changed in the 3 weeks prior to baseline, except for corticosteroid doses for which might have changed.

Patients responding to treatment were offered up to 6 months of extended treatment. Assessments for safety included laboratory safety tests, ECGs, physical exams, ocular exams, vital signs and the monitoring of adverse events. Study participation varied from a minimum of 3 months to a maximum of 9 months.

Condition or Disease	Intervention/Treatment	Phase
Non-infectious Intermediate Uveitis; Non-infectious Posterior Uveitis; Non-infectious Panuveitis	Drug: LFG316; Drug: Conventional Therapy	Phase 2

Detailed Description

Approximately 24 patients with active non-infectious uveitis, in at least one eye, requiring intensification of systemic immunosuppressive therapy were enrolled and randomized to receive intravitreal LFG316 or conventional therapy (investigator's discretion). Only one eye (the study eye) were treated with LFG316 and the other eye (fellow eye) were treated at the investigator's discretion.Throughout the study, the fellow eye might have been treated as needed; except that certain systemic medications were prohibited. There was 1 screening and 8 scheduled visits over 85 days for a total of 9 site visits for all patients.

At Day 85, patients receiving LFG316 treatment who met the criteria for a 'responder', were offered an additional 6 months of LFG316 treatment on a PRN basis. Additional 3 scheduled visits were attended by LFG316-responder patients during the extension period. However, patients could have unscheduled visits as needed and as determined by the investigator. Safety evaluation and ocular assessments were performed throughout the study duration. Patients in the treatment extension phase, who experienced a flare post their last dose and required treatment, might have received a dose of LFG316. These patients were assessed for a response at their next PRN visit as scheduled by the investigator. Visit frequency was determined by the investigator. If they continued to respond to LFG316 therapy, they might have remained in the PRN treatment arm. They might have received up to 7 additional doses of LFG316 in the PRN period. Throughout the trial LFG316 were not administered more frequently than monthly. Patients in the extension phase, who discontinued treatment prematurely were asked to return approximately 1 month after their last dose. Low molecular weight non-steroidal immunosuppressive medications were allowed up to the baseline day as long as the dose had not changed in the 3 weeks prior to baseline, except for corticosteroid doses which might have changed.

Study Design

• Study Type: Interventional
• Actual Enrollment: 25 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Active-controlled, Open-label, Multicenter proof-of Concept Study of Intravitreal LFG316 in Patients With Active Non-infectious Intermediate-, Posterior-, or Panuveitis Requiring Systemic Immunosuppressive Therapy
• Actual Study Start Date: Dec 20, 2012
• Actual Primary Completion Date: Feb 16, 2017
• Actual Study Completion Date: Aug 24, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LFG316 -Intravitreal Injection	Drug: LFG316; LFG316 administered intravitreally (IVT)
Active Comparator: Conventional Therapy	Drug: Conventional Therapy; Conventional Therapy administered in accordance with its prescribing info.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Response Rate for the Individual Response Criteria - in the Study Eye [Day 85 (end of study)]

   Response rate as defined by: An improvement of 2 or more steps in vitreous haze (scale of 0 to 4), relative to baseline OR An improvement of 10 or more letters in visual acuity (VA), relative to baseline OR An improvement of 2 or more steps in anterior chamber cells (ACC) score (scale of 0 to 4), relative to baseline OR Absence of chorioretinal lesions as determined by the investigator

2. Number of Participants With Remission in Study Eye - Treatment Period [Day 85 (end of study)]

   Remission (complete response) was defined as any patient who had: a vitreous haze score of 0 or 0.5 (scale of 0 to 4) in the study eye, AND an anterior chamber cell score of 0 (scale of 0 to 4), AND no chorioretinal lesions in the study eye, AND was off all immune modulatory therapy (systemic, corticosteroids and topical), AND without any worsening of uveitis during the trial.

Secondary Outcome Measures

1. Number of Participants With Vitreous Haze Score in Study Eye - Treatment Period [Day 2, 8, 15, 29, 43, 57 and, 85 (end of the study)]

   Vitreous haze score (based on funduscopic exam): 0, 0.5/Trace, 1+, 2+, 3+, 4+ Vitreous haze score (scale of 0 to 4) with a score of 4 being the most hazed.

2. Mean Best Corrected Visual Acuity (BCVA) in Study Eye - Treatment Period [Day 2, 8, 15, 29, 43, 57 and, 85 (end of the study)]

   Visual acuity was measured using Early Treatment Diabetic Retinopathy Study (ETDRS) eye charts under ETDRS conditions. ETDRS best-corrected visual acuity was obtained in each eye separately under certified ETDRS conditions. This assessment was to be performed prior to pupil dilation. The number of letters read correctly (for each eye) was recorded. BCVA is based on the number of letters read correctly.

3. Number of Patients With Macular Edema in Study Eye - Treatment Period [Day 85 (end of study)]

   Macular edema is a sign of uveitis.

4. Number of Patients With Chorioretinal Lesions in Study Eye - Treatment Period [Day 2, 8, 15, 29, 43, 57 and, 85 (end of the study)]

   Chorioretinal lesions is a sign of uveitis.

5. Number of Participants With Anterior Chamber Cells Score in Study Eye - Treatment Period [Day 2, 8, 15, 29, 43, 57 and, 85 (end of the study)]

   anterior chamber cells score (ACCS) with the scores being 0 (≤ 1 cell), 0.5 (1 to 5 aqueous cells), 1 (6 to 15 aqueous cells), 2 (16 to 25 aqueous cells), 3 (26 to 50 aqueous cells), 4 (>50 aqueous cells).

6. Number of Participants With or Without Anti-LFG316 Antibodies [Throughout the study (treatment and extension period), up to day 271]

   Blood will be collected at each visit for the profiling of serum drug concentrations. The summary of immunogenicity (IG) by visit . The immunogenicity data (presence/absence of anti-LFG316 antibodies [anti-drug antibodies]). NO: No immunogenicity; YES: Positive immunogenicity.

7. Mean Percent Change in Total C5 Concentrations in Serum - Treatment Period [Day 2, 15, 29, 43, 57 and, 85 (end of the study)]

   Percent change from baseline (using each patient's pre-dose value as baseline) in total C5 concentrations.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

• Male or female patients 18 years or older

• Active NIU, in at least one eye, as defined below, in patients requiring intensification of systemic immunosuppressive therapy;

• Vitreous haze at least 1+ on the scale of Nussenblatt et al 1985,or

• Chorioretinal lesions due to uveitis (chorioretinal lesions due to infectious uveitis excluded)

• Patients with a flare and at the time of the enrollment on systemic corticosteroid or non-steroidal immunosuppressants had their therapy tapered or stopped, respectively, at the time of intravitreal LFG316 administration.

Visual acuity (ETDRS method) of 20 letters (20/400 Snellen equivalent) or better in the study eye.

• For female patients, must not be pregnant or lactating and must, unless post-menopausal, use effective contraception.

• Ability to provide informed consent and comply with the protocol.

Key Exclusion Criteria:

• Uveitis so severe that, in the investigator's judgment, it was too risky to test an experimental drug

• Any biologic immunosuppressive agent given via intravitreal, intravenous or subcutaneous route within 4-12 months depending on the agent.

• History of infectious uveitis or endophthalmitis in either eye.

• History of retinal detachment

• Any intraocular surgery, intravitreal injection, periocular injection, or laser photocoagulation to the study eye within 90 days prior to dosing.

• In the study eye, cataract expected to interfere with study conduct or require surgery during the study.

• Forms of uveitis that may have spontaneously resolved

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Golden	Colorado	United States	80401
2	Novartis Investigative Site	Marietta	Georgia	United States	30060
3	Novartis Investigative Site	Cambridge	Massachusetts	United States	02142
4	Novartis Investigative Site	Omaha	Nebraska	United States	68198-5540
5	Novartis Investigative Site	Teaneck	New Jersey	United States	07666
6	Novartis Investigative Site	Houston	Texas	United States	77030
7	Novartis Investigative Site	Bristol		United Kingdom	BS1 2LX
8	Novartis Investigative Site	London		United Kingdom	EC1V 2PD

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

• Statistical Analysis Plan - Aug 28, 2017
• Study Protocol - Sep 7, 2015

More Information

Additional Information:

• A Plain Language Trial Summary is available on novartisclinicatrials.com

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01526889
• Other Study ID Numbers: CLFG316A2204; 2011-003254-90
• First Posted: Feb 6, 2012
• Last Update Posted: Jan 5, 2021
• Last Verified: Oct 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Novartis Pharmaceuticals: Non-infectious uveitis; Panuveitis; Visual acuity; Vitreous Haze; Inflammation of the uvea; inflammation of the middle, pigmented vascular structures of the eye, iris, ciliary body, choroid plexus
• Additional relevant MeSH terms: Uveitis; Panuveitis; Uveitis, Posterior; Uveitis, Intermediate; Pars Planitis

Study Results

Participant Flow

Pre-assignment Detail	Approximately 24 patients were planned to be enrolled. A total of 25 patients were randomized (18 patients in LFG316 group and 7 patients in conventional therapy group).

Arm/Group Title	LFG316	Conventional Therapy
Arm/Group Description	LFG316 administered intravitreally	Conventional treatment was selected by the investigator
Period Title: Treatment Period
STARTED	18	7
COMPLETED	16	7
NOT COMPLETED	2	0
Period Title: Treatment Period
STARTED	5	0
COMPLETED	4	0
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	LFG316	Conventional Therapy	Total
Arm/Group Description	LFG316 administered intravitreally	Conventional treatment was selected by the investigator	Total of all reporting groups
Overall Participants	18	7	25
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	45.3 (14.84)	39.1 (14.89)	43.6 (14.81)
Sex: Female, Male (Count of Participants)
Female	7 38.9%	4 57.1%	11 44%
Male	11 61.1%	3 42.9%	14 56%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 11.1%	0 0%	2 8%
Not Hispanic or Latino	16 88.9%	7 100%	23 92%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
Caucasian	17 94.4%	6 85.7%	23 92%
Black	1 5.6%	1 14.3%	2 8%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Response Rate for the Individual Response Criteria - in the Study Eye
Description	Response rate as defined by: An improvement of 2 or more steps in vitreous haze (scale of 0 to 4), relative to baseline OR An improvement of 10 or more letters in visual acuity (VA), relative to baseline OR An improvement of 2 or more steps in anterior chamber cells (ACC) score (scale of 0 to 4), relative to baseline OR Absence of chorioretinal lesions as determined by the investigator
Time Frame	Day 85 (end of study)

Outcome Measure Data

Analysis Population Description

Efficacy 1 analysis set: All patients in the safety analysis set who received any study treatment (LFG316 or conventional treatment) with evaluable efficacy data for at least one efficacy endpoint(s) (ocular assessments) and with no major protocol deviations that had an impact on efficacy data.

Arm/Group Title	LFG316	Conventional Therapy
Arm/Group Description	LFG316 administered intravitreally	Conventional treatment was selected by the investigator
Measure Participants	18	7
Improvement of vitreous haze ≥2 steps (N=15,6)	3 16.7%	3 42.9%
Improvement of VA ≥ 10 letters (N=15,6)	0 0%	1 14.3%
Improvement of ACC score ≥2 steps (N=7, 1)	0 0%	0 0%
Resolution of chorioretinal lesions (N= 3, 0)	0 0%

2. Primary Outcome

Title	Number of Participants With Remission in Study Eye - Treatment Period
Description	Remission (complete response) was defined as any patient who had: a vitreous haze score of 0 or 0.5 (scale of 0 to 4) in the study eye, AND an anterior chamber cell score of 0 (scale of 0 to 4), AND no chorioretinal lesions in the study eye, AND was off all immune modulatory therapy (systemic, corticosteroids and topical), AND without any worsening of uveitis during the trial.
Time Frame	Day 85 (end of study)

Outcome Measure Data

Analysis Population Description

Efficacy 1 analysis set

Arm/Group Title	LFG316	Conventional Therapy
Arm/Group Description	LFG316 administered intravitreally	Conventional treatment was selected by the investigator
Measure Participants	18	7
Count of Participants [Participants]	2 11.1%	0 0%

3. Secondary Outcome

Title	Number of Participants With Vitreous Haze Score in Study Eye - Treatment Period
Description	Vitreous haze score (based on funduscopic exam): 0, 0.5/Trace, 1+, 2+, 3+, 4+ Vitreous haze score (scale of 0 to 4) with a score of 4 being the most hazed.
Time Frame	Day 2, 8, 15, 29, 43, 57 and, 85 (end of the study)

Outcome Measure Data

Analysis Population Description

Efficacy 1 analysis set

Arm/Group Title	LFG316	Conventional Therapy
Arm/Group Description	LFG316 administered intravitreally	Conventional treatment was selected by the investigator
Measure Participants	18	7
0	0 0%	0 0%
0.5/Trace	2 11.1%	1 14.3%
1+	10 55.6%	4 57.1%
2+	1 5.6%	1 14.3%
3+	2 11.1%	1 14.3%
4+	0 0%	0 0%
0	0 0%	0 0%
0.5/Trace	1 5.6%	0 0%
1+	4 22.2%	1 14.3%
2+	0 0%	0 0%
3+	1 5.6%	0 0%
4+	0 0%	0 0%
0	2 11.1%	1 14.3%
0.5/Trace	3 16.7%	1 14.3%
1+	6 33.3%	4 57.1%
2+	3 16.7%	1 14.3%
3+	0 0%	0 0%
4+	2 11.1%	0 0%
0	0 0%	3 42.9%
0.5/Trace	4 22.2%	1 14.3%
1+	10 55.6%	3 42.9%
2+	0 0%	0 0%
3+	0 0%	0 0%
4+	1 5.6%	0 0%
0	6 33.3%	2 28.6%
0.5/Trace	1 5.6%	3 42.9%
1+	6 33.3%	1 14.3%
2+	0 0%	0 0%
3+	0 0%	0 0%
4+	1 5.6%	0 0%
0	5 27.8%	2 28.6%
0.5/Trace	5 27.8%	2 28.6%
1+	4 22.2%	3 42.9%
2+	0 0%	0 0%
3+	0 0%	0 0%
4+	0 0%	0 0%
0	2 11.1%	1 14.3%
0.5/Trace	6 33.3%	3 42.9%
1+	3 16.7%	2 28.6%
2+	3 16.7%	0 0%
3+	1 5.6%	0 0%
4+	0 0%	0 0%

4. Secondary Outcome

Title	Mean Best Corrected Visual Acuity (BCVA) in Study Eye - Treatment Period
Description	Visual acuity was measured using Early Treatment Diabetic Retinopathy Study (ETDRS) eye charts under ETDRS conditions. ETDRS best-corrected visual acuity was obtained in each eye separately under certified ETDRS conditions. This assessment was to be performed prior to pupil dilation. The number of letters read correctly (for each eye) was recorded. BCVA is based on the number of letters read correctly.
Time Frame	Day 2, 8, 15, 29, 43, 57 and, 85 (end of the study)

Outcome Measure Data

Analysis Population Description

Efficacy 1 analysis set

Arm/Group Title	LFG316	Conventional Therapy
Arm/Group Description	LFG316 administered intravitreally	Conventional treatment was selected by the investigator
Measure Participants	18	7
Day 2	72.5 (19.36)	76.1 (0.7)
Day 8	80.5 (11.69)	79.0 (79)
Day 15	68.8 (18.53)	78.9 (9.10)
Day 29	70.3 (19.39)	79.6 (9.47)
Day 43	65.5 (24.45)	77.3 (9.07)
Day 57	72.6 (14.79)	80.1 (10.35)
Day 85	72.1 (15.53)	76.7 (10.25)

5. Secondary Outcome

Title	Number of Patients With Macular Edema in Study Eye - Treatment Period
Description	Macular edema is a sign of uveitis.
Time Frame	Day 85 (end of study)

Outcome Measure Data

Analysis Population Description

Efficacy 1 analysis set

Arm/Group Title	LFG316	Conventional Therapy
Arm/Group Description	LFG316 administered intravitreally	Conventional treatment was selected by the investigator
Measure Participants	10	3
Day 2	2 11.1%	1 14.3%
Day 8	1 5.6%	1 14.3%
Day 15	3 16.7%	0 0%
Day 29	2 11.1%	0 0%
Day 43	2 11.1%	0 0%
Day 57	2 11.1%	0 0%
Day 85 (end of study)	2 11.1%	0 0%

6. Secondary Outcome

Title	Number of Patients With Chorioretinal Lesions in Study Eye - Treatment Period
Description	Chorioretinal lesions is a sign of uveitis.
Time Frame	Day 2, 8, 15, 29, 43, 57 and, 85 (end of the study)

Outcome Measure Data

Analysis Population Description

Efficacy 1 analysis set

Arm/Group Title	LFG316	Conventional Therapy
Arm/Group Description	LFG316 administered intravitreally	Conventional treatment was selected by the investigator
Measure Participants	10	3
Day 2	3 16.7%	0 0%
Day 8	2 11.1%	0 0%
Day 15	4 22.2%	0 0%
Day 29	5 27.8%	0 0%
Day 43	4 22.2%	0 0%
Day 57	5 27.8%	1 14.3%
Day 85 (end of study)	4 22.2%	1 14.3%

7. Secondary Outcome

Title	Number of Participants With Anterior Chamber Cells Score in Study Eye - Treatment Period
Description	anterior chamber cells score (ACCS) with the scores being 0 (≤ 1 cell), 0.5 (1 to 5 aqueous cells), 1 (6 to 15 aqueous cells), 2 (16 to 25 aqueous cells), 3 (26 to 50 aqueous cells), 4 (>50 aqueous cells).
Time Frame	Day 2, 8, 15, 29, 43, 57 and, 85 (end of the study)

Outcome Measure Data

Analysis Population Description

Efficacy 1 analysis set

Arm/Group Title	LFG316	Conventional Therapy
Arm/Group Description	LFG316 administered intravitreally	Conventional treatment was selected by the investigator
Measure Participants	10	3
0; <1 cell	2 11.1%	0 0%
0.5; 1-5 cells	4 22.2%	1 14.3%
1; 6-15 cells	1 5.6%	0 0%
2; 16-25 cells	0 0%	0 0%
3; 26-50 cells	0 0%	0 0%
4; >50 cells	0 0%	0 0%
0; <1 cell	2 11.1%	0 0%
0.5; 1-5 cells	4 22.2%	1 14.3%
1; 6-15 cells	0 0%	0 0%
2; 16-25 cells	0 0%	0 0%
3; 26-50 cells	0 0%	0 0%
4; >50 cells	0 0%	0 0%
0; <1 cell	3 16.7%	1 14.3%
0.5; 1-5 cells	4 22.2%	0 0%
1; 6-15 cells	1 5.6%	0 0%
2; 16-25 cells	0 0%	0 0%
3; 26-50 cells	0 0%	0 0%
4; >50 cells	0 0%	0 0%
0; <1 cell	2 11.1%	1 14.3%
0.5; 1-5 cells	5 27.8%	0 0%
1; 6-15 cells	0 0%	0 0%
2; 16-25 cells	0 0%	0 0%
3; 26-50 cells	0 0%	0 0%
4; >50 cells	0 0%	0 0%
0; <1 cell	5 27.8%	1 14.3%
0.5; 1-5 cells	0 0%	0 0%
1; 6-15 cells	1 5.6%	0 0%
2; 16-25 cells	1 5.6%	0 0%
3; 26-50 cells	0 0%	0 0%
4; >50 cells	0 0%	0 0%
0; <1 cell	5 27.8%	1 14.3%
0.5; 1-5 cells	1 5.6%	1 14.3%
1; 6-15 cells	2 11.1%	0 0%
2; 16-25 cells	0 0%	0 0%
3; 26-50 cells	0 0%	0 0%
4; >50 cells	0 0%	0 0%
0; <1 cell	4 22.2%	3 42.9%
0.5; 1-5 cells	5 27.8%	0 0%
1; 6-15 cells	0 0%	0 0%
2; 16-25 cells	0 0%	0 0%
3; 26-50 cells	0 0%	0 0%
4; >50 cells	0 0%	0 0%

8. Secondary Outcome

Title	Number of Participants With or Without Anti-LFG316 Antibodies
Description	Blood will be collected at each visit for the profiling of serum drug concentrations. The summary of immunogenicity (IG) by visit . The immunogenicity data (presence/absence of anti-LFG316 antibodies [anti-drug antibodies]). NO: No immunogenicity; YES: Positive immunogenicity.
Time Frame	Throughout the study (treatment and extension period), up to day 271

Outcome Measure Data

Analysis Population Description

Pharmacokinetic analysis set: All patients in the safety analysis set with evaluable PK data and with no protocol deviations affecting PK data.

Arm/Group Title	LFG316
Arm/Group Description	LFG316 administered intravitreally
Measure Participants	17
participants with anti-LFG316 antibodies	3 16.7%
participants without anti-LFG316 antibodies	12 66.7%
participants with anti-LFG316 antibodies	3 16.7%
participants without anti-LFG316 antibodies	10 55.6%
participants with anti-LFG316 antibodies	2 11.1%
participants without anti-LFG316 antibodies	9 50%
participants with anti-LFG316 antibodies	1 5.6%
participants without anti-LFG316 antibodies	1 5.6%
participants with anti-LFG316 antibodies	0 0%
participants without anti-LFG316 antibodies	1 5.6%
participants with anti-LFG316 antibodies	1 5.6%
participants without anti-LFG316 antibodies	0 0%

9. Secondary Outcome

Title	Mean Percent Change in Total C5 Concentrations in Serum - Treatment Period
Description	Percent change from baseline (using each patient's pre-dose value as baseline) in total C5 concentrations.
Time Frame	Day 2, 15, 29, 43, 57 and, 85 (end of the study)

Outcome Measure Data

Analysis Population Description

Pharmacodynamic (PD) analysis set: All patients in the safety analysis set with EVALUABLE pharmacodynamics (PD) data (Total C5) and with no major protocol deviations that had an impact on PD data were included in the PD analysis set.

Arm/Group Title	LFG316	Conventional Therapy
Arm/Group Description	LFG316 administered intravitreally	Conventional treatment was selected by the investigator
Measure Participants	15	7
Day 2	6.80 (14.5)	1.02 (5.69)
Day 15	8.21 (15.3)	-1.27 (19.7)
Day 29	10.6 (17.4)	-8.33 (17.5)
Day 43	8.38 (13.4)	6.46 (18.6)
Day 57	6.73 (12.0)	5.98 (40.9)
Day 85	3.21 (22.1)	1.28 (31.3)

Adverse Events

Time Frame	Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 5 years.
Arm/Group Title	LFG316		Conventional Therapy
Arm/Group Description	LF G316 administered intravitreally		Conventional treatment was selected by the investigator
All Cause Mortality
	LFG316		Conventional Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/18 (0%)		0/7 (0%)
Serious Adverse Events
	LFG316		Conventional Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/18 (5.6%)		0/7 (0%)
Eye disorders
Retinal detachment	1/18 (5.6%)		0/7 (0%)
Retinopathy proliferative	1/18 (5.6%)		0/7 (0%)
Infections and infestations
Mycotic endophthalmitis	1/18 (5.6%)		0/7 (0%)
Other (Not Including Serious) Adverse Events
	LFG316		Conventional Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/18 (61.1%)		5/7 (71.4%)
Eye disorders
Cataract	1/18 (5.6%)		0/7 (0%)
Conjunctival haemorrhage	4/18 (22.2%)		0/7 (0%)
Conjunctival hyperaemia	1/18 (5.6%)		0/7 (0%)
Cystoid macular oedema	1/18 (5.6%)		0/7 (0%)
Dry eye	1/18 (5.6%)		1/7 (14.3%)
Eye pain	1/18 (5.6%)		0/7 (0%)
Hypotony of eye	0/18 (0%)		1/7 (14.3%)
Macular fibrosis	1/18 (5.6%)		1/7 (14.3%)
Ocular hypertension	0/18 (0%)		1/7 (14.3%)
Uveitis	4/18 (22.2%)		0/7 (0%)
Visual impairment	1/18 (5.6%)		0/7 (0%)
Vitreous floaters	1/18 (5.6%)		0/7 (0%)
Immune system disorders
Hypersensitivity	1/18 (5.6%)		0/7 (0%)
Infections and infestations
Giardiasis	1/18 (5.6%)		0/7 (0%)
Oral candidiasis	0/18 (0%)		1/7 (14.3%)
Pharyngitis	0/18 (0%)		1/7 (14.3%)
Sinusitis	1/18 (5.6%)		0/7 (0%)
Tooth infection	0/18 (0%)		1/7 (14.3%)
Urinary tract infection	0/18 (0%)		1/7 (14.3%)
Viral upper respiratory tract infection	2/18 (11.1%)		1/7 (14.3%)
Investigations
Alanine aminotransferase increased	0/18 (0%)		1/7 (14.3%)
Blood pressure increased	1/18 (5.6%)		0/7 (0%)
Gamma-glutamyltransferase increased	0/18 (0%)		1/7 (14.3%)
Intraocular pressure increased	3/18 (16.7%)		0/7 (0%)
Optic nerve cup/disc ratio increased	1/18 (5.6%)		0/7 (0%)
Musculoskeletal and connective tissue disorders
Myalgia	1/18 (5.6%)		0/7 (0%)
Nervous system disorders
Headache	1/18 (5.6%)		1/7 (14.3%)
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	0/18 (0%)		1/7 (14.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.