NCT02288559

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

Completed Phase 2 Results posted Last updated 25 September 2019

What this trial tests

Phase 2 trial testing Sham in Geographic Atrophy in 96 participants. Completed in 2 June 2017.

Timeline

30 March 2015

Primary endpoint
2 June 2017

2 June 2017

Quick facts

Lead sponsor	Genentech, Inc.
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	single
Primary purpose	treatment
Enrollment	96
Start date	30 March 2015
Primary completion	2 June 2017
Estimated completion	2 June 2017
Sites	36 locations across United States

Drugs / interventions tested

• Sham
• Lampalizumab — full drug profile →

Conditions studied

• Geographic Atrophy — all drugs for Geographic Atrophy →

Sponsor

Genentech, Inc. — full company profile →

Who can join

60 and older, any sex, with Geographic Atrophy. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline in Geographic Atrophy (GA) Area, as Assessed by Fundus Autofluorescence (FAF) at Week 24 Primary · Baseline, Week 24

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.

Group	Value	95% CI
Sham Q2W	0.614	± 0.188
Sham Q4W	1.121	± 0.179
Lampalizumab Q2W	1.049	± 0.094
Lampalizumab Q4W	0.911	± 0.123

Serum Concentrations of Lampalizumab (Q2W) Secondary · Baseline (Day 1, predose and postdose), Weeks 2,4,8,16 and 24, early termination, unscheduled predose and postdose

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)).

Day 1 (Predose)

Group	Value	95% CI
Lampalizumab Q2W	NA	± NA

Day 1 (Postdose)

Group	Value	95% CI
Lampalizumab Q2W	1.31	± NA

Week 2

Group	Value	95% CI
Lampalizumab Q2W	55.5	± 89.1

Week 4

Group	Value	95% CI
Lampalizumab Q2W	63.6	± 69.4

Week 8

Group	Value	95% CI
Lampalizumab Q2W	64.4	± 83.7

Week 16

Group	Value	95% CI
Lampalizumab Q2W	78.2	± 68.0

Week 24

Group	Value	95% CI
Lampalizumab Q2W	62.7	± 141.4

Early Termination

Group	Value	95% CI
Lampalizumab Q2W	4.92	± 1070.9

Serum Concentrations of Lampalizumab (Q4W) Secondary · Baseline (Day 1, predose and postdose), Weeks 4,8,16 and 24, early termination

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).

Day 1 (Predose)

Group	Value	95% CI
Lampalizumab Q4W	NA	± NA

Day 1 (Postdose)

Group	Value	95% CI
Lampalizumab Q4W	2.08	± NA

Week 4

Group	Value	95% CI
Lampalizumab Q4W	8.52	± 114.3

Week 8

Group	Value	95% CI
Lampalizumab Q4W	10.3	± 84.1

Week 16

Group	Value	95% CI
Lampalizumab Q4W	8.66	± 88.0

Week 24

Group	Value	95% CI
Lampalizumab Q4W	9.92	± 102.0

Early Termination

Group	Value	95% CI
Lampalizumab Q4W	14.1	± NA

Percentage of Participants With Ocular Adverse Events (AEs) Secondary · Baseline up to approximately 30 weeks

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.

Group	Value	95% CI
Sham Q2W	60.0
Sham Q4W	9.1
Lampalizumab Q2W	63.0
Lampalizumab Q4W	63.6

Percentage of Participants With Systemic (Non-ocular) Adverse Events Secondary · Baseline up to approximately 30 weeks

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. Non-ocular AEs were the systemic events.

Group	Value	95% CI
Sham Q2W	40.0
Sham Q4W	63.6
Lampalizumab Q2W	52.2
Lampalizumab Q4W	50.0

Percentage of Participants With Anti-Lampalizumab Antibodies Secondary · Baseline up to approximately 30 weeks

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.

Treatment-induced ADA

Group	Value	95% CI
Sham Q2W	0
Sham Q4W	0
Lampalizumab Q2W	1
Lampalizumab Q4W	1

Treatment-enhanced ADA

Group	Value	95% CI
Sham Q2W	0
Sham Q4W	0
Lampalizumab Q2W	0
Lampalizumab Q4W	0

Adverse events — posted to ClinicalTrials.gov

Time frame: Baseline up to approximately 30 weeks. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Lampalizumab Q2W

Serious: 7/46 (15%)

Deaths: 2/46

Lampalizumab Q4W

Serious: 3/22 (14%)

Deaths: 0/22

Sham Q2W

Serious: 0/10 (0%)

Deaths: 0/10

Sham Q4W

Serious: 1/11 (9%)

Deaths: 0/11

Serious adverse events (13 terms)

Reaction	System	Lampalizumab Q2W	Lampalizumab Q4W	Sham Q2W	Sham Q4W
Scleritis	Eye disorders	—	—	—	—
Uveitis	Eye disorders	—	—	—	—
Cardiac arrest	Cardiac disorders	—	—	—	—
Myocardial infarction	Cardiac disorders	—	—	—	—
Postural orthostatic tachycardia syndrome	Cardiac disorders	—	—	—	—
Abdominal hernia	Gastrointestinal disorders	—	—	—	—
Influenza	Infections and infestations	—	—	—	—
Fall	Injury, poisoning and procedural complications	—	—	—	—
Femoral neck fracture	Injury, poisoning and procedural complications	—	—	—	—
Malignant melanoma in situ	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—
Non-hodgkins lymphoma recurrent	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—
Embolic stroke	Nervous system disorders	—	—	—	—
Presyncope	Nervous system disorders	—	—	—	—

Other adverse events (37 terms — click to expand)

Reaction	System	Lampalizumab Q2W	Lampalizumab Q4W	Sham Q2W	Sham Q4W
Conjunctival haemorrhage	Eye disorders	—	—	—	—
Eye pain	Eye disorders	—	—	—	—
Viral upper respiratory tract infection	Infections and infestations	—	—	—	—
Vitreous floaters	Eye disorders	—	—	—	—
Vitreous detachment	Eye disorders	—	—	—	—
Seasonal allergy	Immune system disorders	—	—	—	—
Fall	Injury, poisoning and procedural complications	—	—	—	—
Squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—
Atrial fibrillation	Cardiac disorders	—	—	—	—
Deafness unilateral	Ear and labyrinth disorders	—	—	—	—
Middle ear effusion	Ear and labyrinth disorders	—	—	—	—
Vertigo	Ear and labyrinth disorders	—	—	—	—
Cataract subcapsular	Eye disorders	—	—	—	—
Photopsia	Eye disorders	—	—	—	—
Posterior capsule opacification	Eye disorders	—	—	—	—
Retinal haemorrhage	Eye disorders	—	—	—	—
Borderline glaucoma	Eye disorders	—	—	—	—
Cataract nuclear	Eye disorders	—	—	—	—
Conjunctival oedema	Eye disorders	—	—	—	—
Eye pruritus	Eye disorders	—	—	—	—
Eyelid ptosis	Eye disorders	—	—	—	—
Neovascular age-related macular degeneration	Eye disorders	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—
Dental caries	Gastrointestinal disorders	—	—	—	—
Cystitis	Infections and infestations	—	—	—	—
Sinusitis	Infections and infestations	—	—	—	—
Tooth infection	Infections and infestations	—	—	—	—
Tooth fracture	Injury, poisoning and procedural complications	—	—	—	—
Blood glucose increased	Investigations	—	—	—	—
Neutrophil count increased	Investigations	—	—	—	—
Prothrombin time prolonged	Investigations	—	—	—	—
White blood cell count increased	Investigations	—	—	—	—
Bursitis	Musculoskeletal and connective tissue disorders	—	—	—	—
Osteoarthritis	Musculoskeletal and connective tissue disorders	—	—	—	—
Device breakage	Product Issues	—	—	—	—
Pleural effusion	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Upper respiratory tract congestion	Respiratory, thoracic and mediastinal disorders	—	—	—	—

Most-reported serious reactions: Scleritis, Uveitis, Cardiac arrest, Myocardial infarction, Postural orthostatic tachycardia syndrome, Abdominal hernia, Influenza, Fall.

Data from ClinicalTrials.gov NCT02288559 adverse events section.

Sponsor's own description

This multicenter, randomized, single-masked, sham injection-controlled study will investigate the exposure-response and safety of lampalizumab administered intravitreally every 2 weeks (Q2W) or every 4 weeks (Q4W) for 24 weeks in participants with geographic atrophy (GA) secondary to age-related macular degeneration (AMD). A safety run-in assessment will be conducted prior to initiating enrollment in the randomized study.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. The renaissance of complement therapeutics.
   Ricklin D, Mastellos DC, Reis ES, Lambris JD. · · 2018 · cited 305× · PMID 29199277 · DOI 10.1038/nrneph.2017.156
2. Targeting the complement system for the management of retinal inflammatory and degenerative diseases.
   Xu H, Chen M. · · 2016 · cited 129× · PMID 26948311 · DOI 10.1016/j.ejphar.2016.03.001
3. CLINICAL ENDPOINTS FOR THE STUDY OF GEOGRAPHIC ATROPHY SECONDARY TO AGE-RELATED MACULAR DEGENERATION.
   Sadda SR, Chakravarthy U, Birch DG, Staurenghi G, et al · · 2016 · cited 114× · PMID 27652913 · DOI 10.1097/iae.0000000000001283
4. The Challenges and Promise of Complement Therapeutics for Ocular Diseases.
   Park DH, Connor KM, Lambris JD. · · 2019 · cited 87× · PMID 31156618 · DOI 10.3389/fimmu.2019.01007
5. Recent Advances in Age-Related Macular Degeneration Therapies.
   Fabre M, Mateo L, Lamaa D, Baillif S, et al · · 2022 · cited 68× · PMID 36014339 · DOI 10.3390/molecules27165089
6. The complement system in the airway epithelium: An overlooked host defense mechanism and therapeutic target?
   Kulkarni HS, Liszewski MK, Brody SL, Atkinson JP. · · 2018 · cited 61× · PMID 29339260 · DOI 10.1016/j.jaci.2017.11.046
7. A Review of Current and Future Management of Geographic Atrophy.
   Sacconi R, Corbelli E, Querques L, Bandello F, et al · · 2017 · cited 50× · PMID 28391446 · DOI 10.1007/s40123-017-0086-6
8. Recent advances in the management of dry age-related macular degeneration: A review.
   Bandello F, Sacconi R, Querques L, Corbelli E, et al · · 2017 · cited 46× · PMID 28529701 · DOI 10.12688/f1000research.10664.1