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

• ClinicalTrials.gov Identifier: NCT02288559
• Recruitment Status: Completed
• First Posted: November 11, 2014
• Results First Posted: February 19, 2019
• Last Update Posted: September 25, 2019
• Sponsor: Genentech, Inc.
• Information provided by (Responsible Party): Genentech, Inc.

Tracking Information

• First Submitted Date: November 7, 2014
• First Posted Date: November 11, 2014
• Results First Submitted Date: January 24, 2019
• Results First Posted Date: February 19, 2019
• Last Update Posted Date: September 25, 2019
• Actual Study Start Date: March 30, 2015
• Actual Primary Completion Date: June 2, 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 24, 2019)

Change From Baseline in Geographic Atrophy (GA) Area, as Assessed by Fundus Autofluorescence (FAF) at Week 24 [ Time Frame: 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.

• Original Primary Outcome Measures (submitted: November 10, 2014): Efficacy: Mean change in GA area, as measured by FAF [ Time Frame: From baseline to Week 24 ]

Current Secondary Outcome Measures (submitted: January 24, 2019)

• Serum Concentrations of Lampalizumab (Q2W) [ Time Frame: 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)).
• Serum Concentrations of Lampalizumab (Q4W) [ Time Frame: 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).
• Percentage of Participants With Ocular Adverse Events (AEs) [ Time Frame: 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.
• Percentage of Participants With Systemic (Non-ocular) Adverse Events [ Time Frame: 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.
• Percentage of Participants With Anti-Lampalizumab Antibodies [ Time Frame: 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.

Original Secondary Outcome Measures (submitted: November 10, 2014)

• Safety (composite outcome measure): Incidence and severity of ocular and non-ocular (systemic) adverse events [ Time Frame: From baseline to Week 24 ]
• Pharmacokinetic profile derived from the serum concentration-time data following administration of lampalizumab [ Time Frame: Up to 24 weeks ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Lampalizumab Intravitreal Injections Administered Every Two Weeks or Every Four Weeks to Participants With Geographic Atrophy
• Official Title: A Phase II, Multicenter, Randomized, Single-Masked, Sham Injection-Controlled Exposure-Response Study of Lampalizumab Intravitreal Injections Administered Every Two Weeks or Every Four Weeks to Patients With Geographic Atrophy
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Participant); Primary Purpose: Treatment
• Condition: Geographic Atrophy

Intervention

• Other: Sham
  Sham injection will be administered as a matching intravitreal injection of lampalizumab.
• Drug: Lampalizumab
  10 mg dose of lampalizumab administered intravitreally

Study Arms

• Experimental: Lampalizumab: Open-label Safety Run-In
  Participants will receive 10 milligrams (mg) lampalizumab intravitreally Q2W during the safety run-in period.
  Intervention: Drug: Lampalizumab
• Experimental: Q2W Lampalizumab: Randomized Treatment
  Participants will receive 10 mg dose of lampalizumab intravitreally Q2W during the 24-week treatment period.
  Intervention: Drug: Lampalizumab
• Experimental: Q4W Lampalizumab: Randomized Treatment
  Participants will receive 10 mg dose of lampalizumab intravitreally Q4W during the 24-week treatment period.
  Intervention: Drug: Lampalizumab
• Sham Comparator: Sham: Randomized Treatment
  Participants randomized to control arms will receive sham injections, that mimics intravitreal injection of lampalizumab.
  Intervention: Other: Sham

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 8, 2017): 96
• Original Estimated Enrollment (submitted: November 10, 2014): 100
• Actual Study Completion Date: June 2, 2017
• Actual Primary Completion Date: June 2, 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Complement Factor I (CFI) profile biomarker-positive result
• Women of child bearing potential and men should remain abstinent or use contraceptive methods

Exclusion Criteria:

• History of vitrectomy surgery, submacular surgery, or other surgical intervention for AMD in study eye
• Previous subfoveal focal laser photocoagulation in study eye
• Laser photocoagulation in the study eye
• Prior treatment with external-beam radiation therapy or transpupillary thermotherapy in study eye
• Previous intravitreal drug administration in study eye. A single intraoperative administration of a corticosteroid during cataract surgery at least 3 months prior to screening is permitted
• Previous cell-based intraocular treatment in study eye
• Intraocular surgery in study eye
• Uncontrolled glaucoma and history of glaucoma-filtering surgery in study eye
• History of corneal transplant in study eye
• GA in either eye due to causes other than AMD
• Proliferative diabetic retinopathy in either eye
• Active or history of neovascular (wet) AMD in either eye
• History of idiopathic or autoimmune-associated uveitis, ocular or intraocular conditions, and infectious or inflammatory ocular disease
• Active uveitis and infectious conjunctivitis, keratitis, scleritis or endophthalmitis
• Previous systemic treatment with complement inhibitor and with inhibitors/modulators of visual cycle
• Previous expression vector mediated intraocular treatments
• Uncontrolled blood pressure and atrial fibrillation
• Medical conditions associated with clinically significant risk for bleeding-
• Predisposition or history of increased risk for infection
• Active malignancy within the previous 12 months except for appropriately treated carcinoma in situ of cervix, resolved non-melanoma skin carcinoma, and prostate cancer with a Gleason score of less than or equal to 6, and a stable prostate-specific antigen for greater than or equal to (>/=) 12 months
• History of severe allergic reaction or anaphylactic reaction to a biologic agent or known hypersensitivity to any component of lampalizumab injection
• Women of child bearing potential must have a negative serum pregnancy test within 28 days prior to initiation of study treatment
• Previous participation in other studies of investigational drugs

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 60 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02288559
• Other Study ID Numbers: GX29455
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Genentech, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Genentech, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

• PRS Account: Genentech, Inc.
• Verification Date: September 2019