Trial Outcomes & Findings for A Study of Lampalizumab Intravitreal Injections Administered Every Two Weeks or Every Four Weeks to Participants With Geographic Atrophy (NCT NCT02288559)

Last Updated: 2019-09-25

Results Overview

GA or the death of photoreceptors and surrounding cells in the retina, is a common condition in participants with age-related macular degeneration (AMD). The death of these photoreceptors results in lesions that cause vision loss. The change in GA lesion area was measured by FAF and analysis of FAF images was performed by the central reading center. A positive change from baseline indicates an increase in size of geographic atrophy lesion area (worsening; disease progression). BCVA=best corrected visual acuity; ETDRS=Early Treatment Diabetic Retinopathy Scale.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

96 participants

Primary outcome timeframe

Baseline, Week 24

Results posted on

2019-09-25

Participant Flow

A total of 332 participants were screened and 92 participants were randomized out of which 3 participants from one site were removed from the randomized population due to serious good clinical practice (GCP) noncompliance. Out of 89, 4 participants were excluded from the randomized population as they did not have any post-baseline measurement. .

Participant milestones

Participant milestones
Measure	Sham Q2W Participants received sham comparator Q2W (once every 2 weeks) for 24 weeks.	Sham Q4W Participants received sham comparator Q4W (once every 4 weeks) for 24 weeks.	Lampalizumab Q2W Participants received 10 milligrams (mg) dose of lampalizumab administered by intravitreal injections Q2W for 24 weeks.	Lampalizumab Q4W Participants received 10 mg dose of lampalizumab administered by intravitreal injections Q4W for 24 weeks.
Overall Study STARTED	10	11	46	22
Overall Study COMPLETED	9	10	35	20
Overall Study NOT COMPLETED	1	1	11	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Sham Q2W Participants received sham comparator Q2W (once every 2 weeks) for 24 weeks.	Sham Q4W Participants received sham comparator Q4W (once every 4 weeks) for 24 weeks.	Lampalizumab Q2W Participants received 10 milligrams (mg) dose of lampalizumab administered by intravitreal injections Q2W for 24 weeks.	Lampalizumab Q4W Participants received 10 mg dose of lampalizumab administered by intravitreal injections Q4W for 24 weeks.
Overall Study Adverse Event	1	1	5	0
Overall Study Death	0	0	1	0
Overall Study Lost to Follow-up	0	0	0	1
Overall Study Withdrawal by Subject	0	0	2	1
Overall Study Reason Not Specified	0	0	3	0

Baseline Characteristics

A Study of Lampalizumab Intravitreal Injections Administered Every Two Weeks or Every Four Weeks to Participants With Geographic Atrophy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sham Q2W n=10 Participants Participants received sham comparator Q2W (once every 2 weeks) for 24 weeks.	Sham Q4W n=10 Participants Participants received sham comparator Q4W (once every 4 weeks) for 24 weeks.	Lampalizumab Q2W n=43 Participants Participants received 10 milligrams (mg) dose of lampalizumab administered by intravitreal injections Q2W for 24 weeks.	Lampalizumab Q4W n=22 Participants Participants received 10 mg dose of lampalizumab administered by intravitreal injections Q4W for 24 weeks.	Total n=85 Participants Total of all reporting groups
Age, Continuous	73.4 years STANDARD_DEVIATION 4.4 • n=5 Participants	78.2 years STANDARD_DEVIATION 7.7 • n=7 Participants	78.3 years STANDARD_DEVIATION 8.0 • n=5 Participants	80.1 years STANDARD_DEVIATION 7.7 • n=4 Participants	78.2 years STANDARD_DEVIATION 7.7 • n=21 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	8 Participants n=7 Participants	25 Participants n=5 Participants	9 Participants n=4 Participants	49 Participants n=21 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	2 Participants n=7 Participants	18 Participants n=5 Participants	13 Participants n=4 Participants	36 Participants n=21 Participants
Race/Ethnicity, Customized Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	10 Participants n=5 Participants	10 Participants n=7 Participants	42 Participants n=5 Participants	22 Participants n=4 Participants	84 Participants n=21 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
Race/Ethnicity, Customized White	9 Participants n=5 Participants	9 Participants n=7 Participants	42 Participants n=5 Participants	22 Participants n=4 Participants	82 Participants n=21 Participants
Geographic Atrophy Area, as Assessed by Fundus Autofluorescence (FAF)	7.034 millimeter square (mm^2) STANDARD_DEVIATION 2.747 • n=5 Participants	6.891 millimeter square (mm^2) STANDARD_DEVIATION 3.050 • n=7 Participants	8.755 millimeter square (mm^2) STANDARD_DEVIATION 4.059 • n=5 Participants	7.172 millimeter square (mm^2) STANDARD_DEVIATION 4.192 • n=4 Participants	7.923 millimeter square (mm^2) STANDARD_DEVIATION 3.894 • n=21 Participants

PRIMARY outcome

Timeframe: Baseline, Week 24

Population: Modified intent-to-treat (mITT) population included participants who were randomly assigned to study treatment and had at least one post-baseline GA area measurement. Number analyzed is the number of participants with data available for analysis at the given time-point.

Outcome measures

Outcome measures
Measure	Sham Q2W n=10 Participants Participants received sham comparator Q2W (once every 2 weeks) for 24 weeks.	Sham Q4W n=10 Participants Participants received sham comparator Q4W (once every 4 weeks) for 24 weeks.	Lampalizumab Q2W n=43 Participants Participants received 10 milligrams (mg) dose of lampalizumab administered by intravitreal injections Q2W for 24 weeks.	Lampalizumab Q4W n=22 Participants Participants received 10 mg dose of lampalizumab administered by intravitreal injections Q4W for 24 weeks.
Change From Baseline in Geographic Atrophy (GA) Area, as Assessed by Fundus Autofluorescence (FAF) at Week 24	0.614 mm^2 Standard Error 0.188	1.121 mm^2 Standard Error 0.179	1.049 mm^2 Standard Error 0.094	0.911 mm^2 Standard Error 0.123

SECONDARY outcome

Timeframe: Baseline (Day 1, predose and postdose), Weeks 2,4,8,16 and 24, early termination, unscheduled predose and postdose

Population: Pharmacokinetics (PK) population included participants randomized to lampalizumab treatment who received at least one dose of study drug and provided at least one serum sample for determination of lampalizumab. Number analyzed is the number of participants with data available for analysis at the given time-point.

Lower than reportable (LTR) results on pre-dose sample were set to 0, and LTR results on post-dose sample were set to half of lower limit of quantification (LLOQ) (0.5 nanograms per milliliter (ng/mL)).

Outcome measures

Outcome measures
Measure	Sham Q2W n=46 Participants Participants received sham comparator Q2W (once every 2 weeks) for 24 weeks.	Sham Q4W Participants received sham comparator Q4W (once every 4 weeks) for 24 weeks.	Lampalizumab Q2W Participants received 10 milligrams (mg) dose of lampalizumab administered by intravitreal injections Q2W for 24 weeks.	Lampalizumab Q4W Participants received 10 mg dose of lampalizumab administered by intravitreal injections Q4W for 24 weeks.
Serum Concentrations of Lampalizumab (Q2W) Week 8	64.4 ng/mL Geometric Coefficient of Variation 83.7	—	—	—
Serum Concentrations of Lampalizumab (Q2W) Week 16	78.2 ng/mL Geometric Coefficient of Variation 68.0	—	—	—
Serum Concentrations of Lampalizumab (Q2W) Early Termination	4.92 ng/mL Geometric Coefficient of Variation 1070.9	—	—	—
Serum Concentrations of Lampalizumab (Q2W) Unscheduled predose	0.500 ng/mL Geometric Coefficient of Variation NA Geometric coefficient of variation was not calculable as more than one-third of the values were LTR.	—	—	—
Serum Concentrations of Lampalizumab (Q2W) Day 1 (Predose)	NA ng/mL Geometric Coefficient of Variation NA Geometric mean and geometric coefficient of variation were not calculable as more than one-third of the values were LTR.	—	—	—
Serum Concentrations of Lampalizumab (Q2W) Day 1 (Postdose)	1.31 ng/mL Geometric Coefficient of Variation NA Geometric coefficient of variation was not calculable as more than one-third of the values were LTR.	—	—	—
Serum Concentrations of Lampalizumab (Q2W) Week 2	55.5 ng/mL Geometric Coefficient of Variation 89.1	—	—	—
Serum Concentrations of Lampalizumab (Q2W) Week 4	63.6 ng/mL Geometric Coefficient of Variation 69.4	—	—	—
Serum Concentrations of Lampalizumab (Q2W) Week 24	62.7 ng/mL Geometric Coefficient of Variation 141.4	—	—	—
Serum Concentrations of Lampalizumab (Q2W) Unscheduled postdose	0.500 ng/mL Geometric Coefficient of Variation NA Geometric coefficient of variation was not calculable as more than one-third of the values were LTR.	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1, predose and postdose), Weeks 4,8,16 and 24, early termination

Population: PK population included participants randomized to lampalizumab treatment who received at least one dose of study drug and provided at least one serum sample for determination of lampalizumab. Number analyzed is the number of participants with data available for analysis at the given time-point.

LTR results on pre-dose sample were set to 0, and LTR results on post-dose sample were set to half of LLOQ (0.5 ng/mL).

Outcome measures

Outcome measures
Measure	Sham Q2W n=23 Participants Participants received sham comparator Q2W (once every 2 weeks) for 24 weeks.	Sham Q4W Participants received sham comparator Q4W (once every 4 weeks) for 24 weeks.	Lampalizumab Q2W Participants received 10 milligrams (mg) dose of lampalizumab administered by intravitreal injections Q2W for 24 weeks.	Lampalizumab Q4W Participants received 10 mg dose of lampalizumab administered by intravitreal injections Q4W for 24 weeks.
Serum Concentrations of Lampalizumab (Q4W) Day 1 (Postdose)	2.08 ng/mL Geometric Coefficient of Variation NA Geometric coefficient of variation was not calculable as more than one-third of the values were LTR.	—	—	—
Serum Concentrations of Lampalizumab (Q4W) Week 4	8.52 ng/mL Geometric Coefficient of Variation 114.3	—	—	—
Serum Concentrations of Lampalizumab (Q4W) Week 8	10.3 ng/mL Geometric Coefficient of Variation 84.1	—	—	—
Serum Concentrations of Lampalizumab (Q4W) Week 16	8.66 ng/mL Geometric Coefficient of Variation 88.0	—	—	—
Serum Concentrations of Lampalizumab (Q4W) Week 24	9.92 ng/mL Geometric Coefficient of Variation 102.0	—	—	—
Serum Concentrations of Lampalizumab (Q4W) Early Termination	14.1 ng/mL Geometric Coefficient of Variation NA Geometric coefficient of variation was not calculable as more than one-third of the values were LTR.	—	—	—
Serum Concentrations of Lampalizumab (Q4W) Day 1 (Predose)	NA ng/mL Geometric Coefficient of Variation NA Geometric mean and geometric coefficient of variation were not calculable as more than one-third of the values were LTR.	—	—	—

SECONDARY outcome

Timeframe: Baseline up to approximately 30 weeks

Population: Safety analysis population included all randomized participants who received at least one dose of study drug.

An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether considered related to the medicinal product, any new disease or exacerbation of an existing disease, recurrence of an intermittent medical condition, or any deterioration in a laboratory value or other clinical test. Ocular AEs are the events which are localized in the ocular region.

Outcome measures

Outcome measures
Measure	Sham Q2W n=10 Participants Participants received sham comparator Q2W (once every 2 weeks) for 24 weeks.	Sham Q4W n=11 Participants Participants received sham comparator Q4W (once every 4 weeks) for 24 weeks.	Lampalizumab Q2W n=46 Participants Participants received 10 milligrams (mg) dose of lampalizumab administered by intravitreal injections Q2W for 24 weeks.	Lampalizumab Q4W n=22 Participants Participants received 10 mg dose of lampalizumab administered by intravitreal injections Q4W for 24 weeks.
Percentage of Participants With Ocular Adverse Events (AEs)	60.0 percentage of participants	9.1 percentage of participants	63.0 percentage of participants	63.6 percentage of participants

SECONDARY outcome

Timeframe: Baseline up to approximately 30 weeks

Population: Safety analysis population included all randomized participants who received at least one dose of study drug.

Outcome measures

Outcome measures
Measure	Sham Q2W n=10 Participants Participants received sham comparator Q2W (once every 2 weeks) for 24 weeks.	Sham Q4W n=11 Participants Participants received sham comparator Q4W (once every 4 weeks) for 24 weeks.	Lampalizumab Q2W n=46 Participants Participants received 10 milligrams (mg) dose of lampalizumab administered by intravitreal injections Q2W for 24 weeks.	Lampalizumab Q4W n=22 Participants Participants received 10 mg dose of lampalizumab administered by intravitreal injections Q4W for 24 weeks.
Percentage of Participants With Systemic (Non-ocular) Adverse Events	40.0 percentage of participants	63.6 percentage of participants	52.2 percentage of participants	50.0 percentage of participants

SECONDARY outcome

Timeframe: Baseline up to approximately 30 weeks

Population: Safety analysis population included all randomized participants who received at least one dose of study drug. Number analyzed is the number of participants with data available for analysis at the given time-point.

Having treatment-induced anti-drug antibodies (ADAs) was defined as being ADA-negative at baseline and ADA-positive at any post-baseline timepoint. Having treatment-enhanced ADAs was defined as being ADA-positive at baseline with titer values increased by 0.6 titer units at any post-baseline timepoint.

Outcome measures

Outcome measures
Measure	Sham Q2W n=10 Participants Participants received sham comparator Q2W (once every 2 weeks) for 24 weeks.	Sham Q4W n=11 Participants Participants received sham comparator Q4W (once every 4 weeks) for 24 weeks.	Lampalizumab Q2W n=46 Participants Participants received 10 milligrams (mg) dose of lampalizumab administered by intravitreal injections Q2W for 24 weeks.	Lampalizumab Q4W n=22 Participants Participants received 10 mg dose of lampalizumab administered by intravitreal injections Q4W for 24 weeks.
Percentage of Participants With Anti-Lampalizumab Antibodies Treatment-induced ADA	0 percentage of participants	0 percentage of participants	1 percentage of participants	1 percentage of participants
Percentage of Participants With Anti-Lampalizumab Antibodies Treatment-enhanced ADA	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants

Adverse Events

Lampalizumab Q2W

Serious events: 7 serious events

Other events: 21 other events

Deaths: 2 deaths

Lampalizumab Q4W

Serious events: 3 serious events

Other events: 13 other events

Deaths: 0 deaths

Sham Q2W

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Sham Q4W

Serious events: 1 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Lampalizumab Q2W n=46 participants at risk Participants received 10 milligrams (mg) dose of lampalizumab administered by intravitreal injections Q2W for 24 weeks.	Lampalizumab Q4W n=22 participants at risk Participants received 10 mg dose of lampalizumab administered by intravitreal injections Q4W for 24 weeks.	Sham Q2W n=10 participants at risk Participants received sham comparator Q2W (once every 2 weeks) for 24 weeks.	Sham Q4W n=11 participants at risk Participants received sham comparator Q4W (once every 4 weeks) for 24 weeks.
Eye disorders Scleritis	2.2% 1/46 • Baseline up to approximately 30 weeks Safety analysis population included all randomized participants who received at least one dose of study drug.	0.00% 0/22 • Baseline up to approximately 30 weeks Safety analysis population included all randomized participants who received at least one dose of study drug.	0.00% 0/10 • Baseline up to approximately 30 weeks Safety analysis population included all randomized participants who received at least one dose of study drug.	0.00% 0/11 • Baseline up to approximately 30 weeks Safety analysis population included all randomized participants who received at least one dose of study drug.
Eye disorders Uveitis	2.2% 1/46 • Baseline up to approximately 30 weeks Safety analysis population included all randomized participants who received at least one dose of study drug.	0.00% 0/22 • Baseline up to approximately 30 weeks Safety analysis population included all randomized participants who received at least one dose of study drug.	0.00% 0/10 • Baseline up to approximately 30 weeks Safety analysis population included all randomized participants who received at least one dose of study drug.	0.00% 0/11 • Baseline up to approximately 30 weeks Safety analysis population included all randomized participants who received at least one dose of study drug.
Cardiac disorders Cardiac arrest	2.2% 1/46 • Baseline up to approximately 30 weeks Safety analysis population included all randomized participants who received at least one dose of study drug.	0.00% 0/22 • Baseline up to approximately 30 weeks Safety analysis population included all randomized participants who received at least one dose of study drug.	0.00% 0/10 • Baseline up to approximately 30 weeks Safety analysis population included all randomized participants who received at least one dose of study drug.	0.00% 0/11 • Baseline up to approximately 30 weeks Safety analysis population included all randomized participants who received at least one dose of study drug.
Cardiac disorders Myocardial infarction	2.2% 1/46 • Baseline up to approximately 30 weeks Safety analysis population included all randomized participants who received at least one dose of study drug.	0.00% 0/22 • Baseline up to approximately 30 weeks Safety analysis population included all randomized participants who received at least one dose of study drug.	0.00% 0/10 • Baseline up to approximately 30 weeks Safety analysis population included all randomized participants who received at least one dose of study drug.	0.00% 0/11 • Baseline up to approximately 30 weeks Safety analysis population included all randomized participants who received at least one dose of study drug.
Cardiac disorders Postural orthostatic tachycardia syndrome	0.00% 0/46 • Baseline up to approximately 30 weeks Safety analysis population included all randomized participants who received at least one dose of study drug.	4.5% 1/22 • Baseline up to approximately 30 weeks Safety analysis population included all randomized participants who received at least one dose of study drug.	0.00% 0/10 • Baseline up to approximately 30 weeks Safety analysis population included all randomized participants who received at least one dose of study drug.	0.00% 0/11 • Baseline up to approximately 30 weeks Safety analysis population included all randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal hernia	2.2% 1/46 • Baseline up to approximately 30 weeks Safety analysis population included all randomized participants who received at least one dose of study drug.	0.00% 0/22 • Baseline up to approximately 30 weeks Safety analysis population included all randomized participants who received at least one dose of study drug.	0.00% 0/10 • Baseline up to approximately 30 weeks Safety analysis population included all randomized participants who received at least one dose of study drug.	0.00% 0/11 • Baseline up to approximately 30 weeks Safety analysis population included all randomized participants who received at least one dose of study drug.
Infections and infestations Influenza	0.00% 0/46 • Baseline up to approximately 30 weeks Safety analysis population included all randomized participants who received at least one dose of study drug.	4.5% 1/22 • Baseline up to approximately 30 weeks Safety analysis population included all randomized participants who received at least one dose of study drug.	0.00% 0/10 • Baseline up to approximately 30 weeks Safety analysis population included all randomized participants who received at least one dose of study drug.	0.00% 0/11 • Baseline up to approximately 30 weeks Safety analysis population included all randomized participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Fall	2.2% 1/46 • Baseline up to approximately 30 weeks Safety analysis population included all randomized participants who received at least one dose of study drug.	4.5% 1/22 • Baseline up to approximately 30 weeks Safety analysis population included all randomized participants who received at least one dose of study drug.	0.00% 0/10 • Baseline up to approximately 30 weeks Safety analysis population included all randomized participants who received at least one dose of study drug.	0.00% 0/11 • Baseline up to approximately 30 weeks Safety analysis population included all randomized participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Femoral neck fracture	2.2% 1/46 • Baseline up to approximately 30 weeks Safety analysis population included all randomized participants who received at least one dose of study drug.	0.00% 0/22 • Baseline up to approximately 30 weeks Safety analysis population included all randomized participants who received at least one dose of study drug.	0.00% 0/10 • Baseline up to approximately 30 weeks Safety analysis population included all randomized participants who received at least one dose of study drug.	0.00% 0/11 • Baseline up to approximately 30 weeks Safety analysis population included all randomized participants who received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma in situ	2.2% 1/46 • Baseline up to approximately 30 weeks Safety analysis population included all randomized participants who received at least one dose of study drug.	0.00% 0/22 • Baseline up to approximately 30 weeks Safety analysis population included all randomized participants who received at least one dose of study drug.	0.00% 0/10 • Baseline up to approximately 30 weeks Safety analysis population included all randomized participants who received at least one dose of study drug.	0.00% 0/11 • Baseline up to approximately 30 weeks Safety analysis population included all randomized participants who received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-hodgkins lymphoma recurrent	0.00% 0/46 • Baseline up to approximately 30 weeks Safety analysis population included all randomized participants who received at least one dose of study drug.	0.00% 0/22 • Baseline up to approximately 30 weeks Safety analysis population included all randomized participants who received at least one dose of study drug.	0.00% 0/10 • Baseline up to approximately 30 weeks Safety analysis population included all randomized participants who received at least one dose of study drug.	9.1% 1/11 • Baseline up to approximately 30 weeks Safety analysis population included all randomized participants who received at least one dose of study drug.
Nervous system disorders Embolic stroke	0.00% 0/46 • Baseline up to approximately 30 weeks Safety analysis population included all randomized participants who received at least one dose of study drug.	4.5% 1/22 • Baseline up to approximately 30 weeks Safety analysis population included all randomized participants who received at least one dose of study drug.	0.00% 0/10 • Baseline up to approximately 30 weeks Safety analysis population included all randomized participants who received at least one dose of study drug.	0.00% 0/11 • Baseline up to approximately 30 weeks Safety analysis population included all randomized participants who received at least one dose of study drug.
Nervous system disorders Presyncope	0.00% 0/46 • Baseline up to approximately 30 weeks Safety analysis population included all randomized participants who received at least one dose of study drug.	0.00% 0/22 • Baseline up to approximately 30 weeks Safety analysis population included all randomized participants who received at least one dose of study drug.	0.00% 0/10 • Baseline up to approximately 30 weeks Safety analysis population included all randomized participants who received at least one dose of study drug.	9.1% 1/11 • Baseline up to approximately 30 weeks Safety analysis population included all randomized participants who received at least one dose of study drug.

Other adverse events

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: (+41) 616878333

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER