Trial Outcomes & Findings for A Study Using Intravitreal Injections of a Small Interfering RNA in Patients With Age-Related Macular Degeneration (NCT NCT00395057)

Last Updated: 2015-09-07

Results Overview

Percentage of patients with improvement in BCVA of 15 or more letters at Month 3. BCVA is measured using an eye chart and is reported as the number of letters read correctly (ranging from 0 to 100 letters). The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

138 participants

Primary outcome timeframe

Month 3

Results posted on

2015-09-07

Participant Flow

Participant milestones

Participant milestones
Measure	AGN 211745 Solution 1000 ug AGN 211745 Solution 1000 ug	AGN 211745 Solution 300 ug AGN 211745 Solution 300 ug	AGN 211745 Solution 100 ug AGN 211745 Solution 100 ug	Ranibizumab 500 ug Ranibizumab 500 ug
Overall Study STARTED	34	35	35	34
Overall Study COMPLETED	2	1	2	1
Overall Study NOT COMPLETED	32	34	33	33

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study Using Intravitreal Injections of a Small Interfering RNA in Patients With Age-Related Macular Degeneration

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	AGN 211745 Solution 1000 ug n=34 Participants AGN 211745 Solution 1000 ug	AGN 211745 Solution 300 ug n=35 Participants AGN 211745 Solution 300 ug	AGN 211745 Solution 100 ug n=35 Participants AGN 211745 Solution 100 ug	Ranibizumab 500 ug n=34 Participants Ranibizumab 500 ug	Total n=138 Participants Total of all reporting groups
Age, Customized Between 45 and 65 years	2 participants n=5 Participants	5 participants n=7 Participants	5 participants n=5 Participants	4 participants n=4 Participants	16 participants n=21 Participants
Age, Customized >=65 years	32 participants n=5 Participants	30 participants n=7 Participants	30 participants n=5 Participants	30 participants n=4 Participants	122 participants n=21 Participants
Sex: Female, Male Female	19 Participants n=5 Participants	19 Participants n=7 Participants	24 Participants n=5 Participants	14 Participants n=4 Participants	76 Participants n=21 Participants
Sex: Female, Male Male	15 Participants n=5 Participants	16 Participants n=7 Participants	11 Participants n=5 Participants	20 Participants n=4 Participants	62 Participants n=21 Participants

PRIMARY outcome

Timeframe: Month 3

Population: Intent-To-Treat (ITT). The ITT population included all patients who started the study (randomized).

Outcome measures

Outcome measures
Measure	AGN 211745 Solution 1000 ug n=34 Participants AGN 211745 Solution 1000 ug	AGN 211745 Solution 300 ug n=35 Participants AGN 211745 Solution 300 ug	AGN 211745 Solution 100 ug n=35 Participants AGN 211745 Solution 100 ug	Ranibizumab 500 ug n=34 Participants Ranibizumab 500 ug
Percentage of Patients With Improvement in Best Corrected Visual Acuity (BCVA) of 15 or More Letters at Month 3	5.9 Percentage of Patients	2.9 Percentage of Patients	0 Percentage of Patients	17.6 Percentage of Patients

SECONDARY outcome

Timeframe: Month 3

Population: Intent-To-Treat. The ITT population included all patients who started the study (randomized).

Lesion size as assessed by FA and photography at month 3. FA is a technique for examining the circulation of the retina (and detecting any leakage) using a dye-tracing method. Photographs are taken with a specialized low-power microscope with an attached camera designed to photograph the interior of the eye, including the retina and optic disc.

Outcome measures

Outcome measures
Measure	AGN 211745 Solution 1000 ug n=34 Participants AGN 211745 Solution 1000 ug	AGN 211745 Solution 300 ug n=35 Participants AGN 211745 Solution 300 ug	AGN 211745 Solution 100 ug n=35 Participants AGN 211745 Solution 100 ug	Ranibizumab 500 ug n=34 Participants Ranibizumab 500 ug
Lesion Size as Assessed by Fluorescein Angiography (FA) and Photography at Month 3	6.17 Millimeters squared (mm^2) Standard Deviation 4.339	4.29 Millimeters squared (mm^2) Standard Deviation 3.264	6.54 Millimeters squared (mm^2) Standard Deviation 6.102	3.89 Millimeters squared (mm^2) Standard Deviation 3.396

SECONDARY outcome

Timeframe: Month 3

Population: Intent-To-Treat (ITT). The ITT population included all patients who started the study (randomized).

Foveal thickness as assessed by OCT at month 3. The fovea is a part of the eye, located in the center of the macula region of the retina. OCT is a laser-based, noninvasive, diagnostic system providing high-resolution, three-dimensional images of the retina. The fovea is responsible for sharp central vision, which is necessary for reading or any activity where visual detail is of primary importance. Normal foveal thickness ranges from 175 to 250 microns. A foveal thickness greater than 250 microns represents worsening vision.

Outcome measures

Outcome measures
Measure	AGN 211745 Solution 1000 ug n=34 Participants AGN 211745 Solution 1000 ug	AGN 211745 Solution 300 ug n=35 Participants AGN 211745 Solution 300 ug	AGN 211745 Solution 100 ug n=35 Participants AGN 211745 Solution 100 ug	Ranibizumab 500 ug n=34 Participants Ranibizumab 500 ug
Foveal Thickness as Assessed by Optical Coherence Tomography (OCT) at Month 3	484.6 Microns Standard Deviation 142.21	413.2 Microns Standard Deviation 103.59	437.1 Microns Standard Deviation 125.46	269.8 Microns Standard Deviation 76.72

SECONDARY outcome

Timeframe: Month 3

Population: Intent-To-Treat (ITT). The ITT population included all patients who started the study (randomized). Data for this outcome measure were not analyzed as the study was terminated early.

Visual Functioning Questionnaire (VFQ) at Month 3. The VFQ includes 25 questions which assess visual impairment on functioning and specific aspects of health-related quality of life. Study terminated; data for this outcome measure were not analyzed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Month 6

Population: Intent-To-Treat (ITT). The ITT population included all patients who started the study (randomized).

Time to treatment with standard-of-care at month 6, defined as the number of days before the use of rescue therapy occurred.

Outcome measures

Outcome measures
Measure	AGN 211745 Solution 1000 ug n=34 Participants AGN 211745 Solution 1000 ug	AGN 211745 Solution 300 ug n=35 Participants AGN 211745 Solution 300 ug	AGN 211745 Solution 100 ug n=35 Participants AGN 211745 Solution 100 ug	Ranibizumab 500 ug n=34 Participants Ranibizumab 500 ug
Time to Treatment With Standard of Care at Month 6	91.0 Number of Days Interval 86.0 to 102.0	91.5 Number of Days Interval 90.0 to 119.0	92.0 Number of Days Interval 91.0 to 112.0	130.5 Number of Days Interval 96.0 to 161.0

Adverse Events

AGN 211745 Solution 1000 ug

Serious events: 4 serious events

Other events: 29 other events

Deaths: 0 deaths

AGN 211745 Solution 300 ug

Serious events: 3 serious events

Other events: 26 other events

Deaths: 0 deaths

AGN 211745 Solution 100 ug

Serious events: 3 serious events

Other events: 28 other events

Deaths: 0 deaths

Ranibizumab 500 ug

Serious events: 9 serious events

Other events: 24 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Therapeutic Area Head

Allergan, Inc.

Phone: 714-246-4500

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee A disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 90 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo
Publication restrictions are in place

Restriction type: OTHER

Measure	AGN 211745 Solution 1000 ug n=34 participants at risk AGN 211745 Solution 1000 ug	AGN 211745 Solution 300 ug n=35 participants at risk AGN 211745 Solution 300 ug	AGN 211745 Solution 100 ug n=35 participants at risk AGN 211745 Solution 100 ug	Ranibizumab 500 ug n=34 participants at risk Ranibizumab 500 ug
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.00% 0/34 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.	0.00% 0/35 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.	0.00% 0/35 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.	2.9% 1/34 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.
Cardiac disorders Angina pectoris	0.00% 0/34 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.	2.9% 1/35 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.	0.00% 0/35 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.	2.9% 1/34 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.
Gastrointestinal disorders Inguinal hernia	0.00% 0/34 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.	0.00% 0/35 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.	2.9% 1/35 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.	0.00% 0/34 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/34 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.	0.00% 0/35 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.	2.9% 1/35 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.	0.00% 0/34 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.
Hepatobiliary disorders Biliary tract disorder	0.00% 0/34 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.	0.00% 0/35 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.	0.00% 0/35 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.	2.9% 1/34 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.
Hepatobiliary disorders Cholelithiasis	0.00% 0/34 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.	0.00% 0/35 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.	0.00% 0/35 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.	2.9% 1/34 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.
Infections and infestations Pneumonia	0.00% 0/34 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.	0.00% 0/35 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.	2.9% 1/35 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.	0.00% 0/34 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.
Infections and infestations Herpes zoster ophthalmic	0.00% 0/34 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.	0.00% 0/35 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.	0.00% 0/35 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.	2.9% 1/34 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.
Infections and infestations Pneumonia legionella	0.00% 0/34 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.	0.00% 0/35 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.	0.00% 0/35 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.	2.9% 1/34 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.
Metabolism and nutrition disorders Dehydration	0.00% 0/34 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.	0.00% 0/35 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.	0.00% 0/35 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.	2.9% 1/34 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Chronic lymphocytic leukaemia	2.9% 1/34 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.	0.00% 0/35 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.	0.00% 0/35 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.	0.00% 0/34 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Leukaemia	2.9% 1/34 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.	0.00% 0/35 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.	0.00% 0/35 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.	0.00% 0/34 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lip neoplasm malignant stage unspecified	2.9% 1/34 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.	0.00% 0/35 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.	0.00% 0/35 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.	0.00% 0/34 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-small cell lung cancer	0.00% 0/34 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.	0.00% 0/35 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.	0.00% 0/35 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.	2.9% 1/34 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.
Nervous system disorders Syncope	0.00% 0/34 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.	2.9% 1/35 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.	0.00% 0/35 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.	0.00% 0/34 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.
Reproductive system and breast disorders Benign prostatic hyperplasia	0.00% 0/34 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.	2.9% 1/35 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.	0.00% 0/35 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.	0.00% 0/34 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.
Vascular disorders Peripheral ischaemia	2.9% 1/34 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.	0.00% 0/35 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.	0.00% 0/35 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.	0.00% 0/34 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.
Vascular disorders Hypertension	0.00% 0/34 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.	0.00% 0/35 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.	0.00% 0/35 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.	2.9% 1/34 The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated.