A PHASE III, MULTICENTER, RANDOMIZED, DOUBLE-MASKED, SHAM-CONTROLLED STUDY TO ASSESS THE EFFICACY AND SAFETY OF LAMPALIZUMAB ADMINISTERED INTRAVITREALLY TO PATIENTS WITH GEOGRAPHIC ATROPHY SECONDARY TO AGE-RELATED MACULAR DEGENERATION
- CTRC Outpatient
- UT Southwestern Ambulatory Services
Rafael Ufret-Vincenty, M.D.
This study is a Phase iii, double-masked, multicenter, randomized, sham injection-controlled study evaluating the efficacy and safety of a 10-mg dose of lampalizumab administered Q4W or Q6W by intravitreal injections for approximately 96 weeks, excluding screening period, in patients with Ga secondary to aMD. The study will randomize approximately 936 patients at approximately 125 investigational sites globally. The study will consist of a screening period of up to 21 days (Days [?]21 to [?]1) and an approximately 2-year treatment period,followed by the final study visit at Week 96. The duration of the study is approximately 2 years (96 weeks) after the last patient is randomized to the study.
each consented patient must satisfy all eligibility criteria at both the screening period and the Day 1 visit. as part of the screening process, the central reading center will evaluate FaF images, CFPs, and fluorescein angiograms (Fa) to provide an objective, masked assessment of patient eligibility. The investigational cobas[RegisteredTM] CFi profile assay results of blood sample analysis will be used to determine a patient's biomarker-positive or -negative status and must be obtained during the screening period prior to Day 1 visit. Patients must also meet BCVa and other eligibility criteria.Screen-failed patients may be eligible for re-screening up to two additional times during the study.only one eye will be chosen as the study eye.if both eyes are eligible, the eye with the worse visual function will be the study eye;if both eyes have the same visual function,the eye with the larger area of Ga will be selected as the study eye. after screening has been completed,eligible patients will be randomized in a 2:1:2:1 ratio so that approximately 312 patients will receive study drug treatment Q4W and 156 patients will receive sham treatment Q4W for a total of 24 treatments;312 patients will receive study drug treatment Q6W and 156 patients will receive sham treatment Q6W for a total of 16 treatments.The study population will be enriched (ratio of 1.5:1) for the biomarker-positive population relative to the biomarker-negative population.Randomization will be stratified by biomarker status (positive vs. negative) (as determined by the investigational cobas[RegisteredTM] CFi Profile assay),baseline BCVa eTDRS chart Snellen equivalent (20/50 or better vs. worse than 20/50), sex (women vs. men), and microperimetry eligibility (yes vs. no).
The primary efficacy endpoint is the mean change in Ga area from baseline at 1 year (Week 48) as assessed by FaF.
The secondary endpoints for this study are as follows:
mean change from baseline in Ga area at 2 years as assessed by FaF,mean change from baseline in Ga area over time (all timepoints) as assessed by FaF,mean change from baseline in BCVa at 2 years as assessed by eTDRS chart at a starting distance of 4 m, mean change from baseline in BCVa over time as assessed by eTDRS chart at a starting distance of 4 m, mean change from baseline in BCVa at 2 years as assessed by eTDRS chart under low luminance conditions at a starting distance of 4 m, mean change from baseline in BCVa over time as assessed by eTDRS chart under low luminance conditions at a starting distance of 4m, proportion of patients with [Less Than] 15 letters loss in BCVa score compared to baseline at 2 years as assessed by eTDRS chart at a starting distance of 4 m and under low luminance conditions, mean change from baseline in mean binocular reading speed at 2 years as assessed by MnRead charts,mean change from baseline in binocular critical print size at 2 years as assessed by MnRead charts,mean change from baseline in nei VFQ-25 composite score at 2 years,mean change from baseline in nei VFQ-25 near activity subscale score at 2 years, mean change from baseline in nei VFQ-25 distance activity subscale score at 2 years,mean change from baseline in FRi index score at 2 years
The control subjects will only be used for photography certification of images and equipment.
General Inclusion Criteria
* Willingness to provide signed informed consent. Additionally, at U.S. sites, patients
must provide Health Insurance Portability and Accountability Act (HIPAA)
authorization, and in other countries, as applicable according to national laws.
* Age >=50 years
* For women who are not postmenopausal (>=12 months of non-therapy-induced
amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to
remain abstinent or use single or combined contraceptive methods that result in a
failure rate of <1% per year during the treatment period and for at least 30 ((+ or -)7) days
after the last dose of study treatment.
Abstinence is only acceptable if it is in line with the preferred and usual lifestyle
of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or
postovulation methods) and withdrawal are not acceptable methods of
Sexually active men will be required to use a barrier contraceptive method
(condom), even if they have been surgically sterilized, for the duration of the
treatment period and for at least 30 ((+ or -)7) days after the last dose of study
* Ability and willingness to undertake all scheduled visits and assessments
* Valid CFI profile biomarker result (i.e., CFI profile biomarker-positive or CFI profile
Ocular Inclusion Criteria: Study Eye
* BCVA of 20/100 or better (Snellen equivalent) using ETDRS charts at starting
distance of 4 m-If BCVA is >= 20/25, at least one GA lesion must be within 250 [MICRO-SYMBOL]m of the foveal
* Well demarcated area(s) of GA secondary to AMD with no evidence of prior or
active CNV: The total GA lesion size >=2.54 mm2 (approximately >=1 disc area [DA]) and
<=17.78 mm2 (approximately <=7 DA) and must reside completely within the FAF imaging field (Field 2[?]30 degree image centered on the fovea) If GA is multifocal, at least 1 focal lesion must be >=1.27 mm2 (approximately >=0.5 DA)
* Presence of hyperautofluorescence of either banded or diffuse patterns adjacent to
the area of GA
* Sufficiently clear ocular media, adequate pupillary dilation, and fixation to permit
quality fundus imaging
Ocular Inclusion Criteria: Non-study Eye
* GA secondary to AMD with no evidence of prior or active CNV
* GA lesion must reside completely within the FAF imaging field (Field 2[?]30 degree
image centered on the fovea)