Zimura in Participants With Geographic Atrophy Secondary to Dry Age-Related Macular Degeneration

• ClinicalTrials.gov Identifier: NCT02686658
• Recruitment Status: Completed
• First Posted: February 19, 2016
• Results First Posted: May 11, 2023
• Last Update Posted: February 23, 2024
• Sponsor: IVERIC bio, Inc.
• Information provided by (Responsible Party): Astellas Pharma Inc ( IVERIC bio, Inc. )

Tracking Information

• First Submitted Date: February 16, 2016
• First Posted Date: February 19, 2016
• Results First Submitted Date: January 27, 2023
• Results First Posted Date: May 11, 2023
• Last Update Posted Date: February 23, 2024
• Actual Study Start Date: January 20, 2016
• Actual Primary Completion Date: September 26, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 18, 2023)

Change From Baseline in Geographic Atrophy as Measured by Fundus Autofluorescence [ Time Frame: Baseline and 12 months ]

The least squares mean change in geographic atrophy (GA) from baseline to Month 12 was measured by fundus autofluorescence (FAF). The square root of the GA area was used in the analysis. Per statistical analysis plan, only the Zimura 2 mg and 4 mg groups were evaluated for this primary endpoint; the Zimura 1 mg group was for descriptive purposes only.

• Original Primary Outcome Measures (submitted: February 18, 2016): The mean change in best corrected visual acuity (Early Treatment Diabetic Retinopathy Study [ETDRS] letters) from Baseline to Month 24 [ Time Frame: 24 months ]

Current Secondary Outcome Measures (submitted: April 18, 2023)

• Change From Baseline in Best Corrected Visual Acuity Using Early Treatment Diabetic Retinopathy Study Letters [ Time Frame: Baseline and 12 months ]
  The least squares mean change in best-corrected visual acuity (BCVA) from baseline to Month 12 was measured using early treatment diabetic retinopathy study [ETDRS] letters. Per statistical analysis plan, only the Zimura 2 mg and 4 mg groups were evaluated for the secondary endpoints; the Zimura 1 mg group was for descriptive purposes only.
• Change From Baseline in Low Luminance BCVA Using Early Treatment Diabetic Retinopathy Study Letters [ Time Frame: Baseline and 12 months ]
  The least squares mean change in low luminance (LL) BCVA from baseline to Month 12 was measured using ETDRS letters. Per statistical analysis plan, only the Zimura 2 mg and 4 mg groups were evaluated for the secondary endpoints; the Zimura 1 mg group was for descriptive purposes only.

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

Descriptive Information

• Brief Title: Zimura in Participants With Geographic Atrophy Secondary to Dry Age-Related Macular Degeneration
• Official Title: A Phase 2/3 Randomized, Double-Masked, Controlled Trial to Assess the Safety and Efficacy of Intravitreous Administration of Zimura™ (Anti-C5 Aptamer) in Subjects With Geographic Atrophy Secondary to Dry Age-Related Macular Degeneration
• Brief Summary: The objectives of this study were to evaluate the safety and efficacy of Zimura intravitreal (IVT) administration when administered in participants with geographic atrophy (GA) secondary to dry age-related macular degeneration (AMD).
• Detailed Description: Participants will receive monthly intravitreal injections of Zimura or Sham for 18 months.
• Study Type: Interventional
• Study Phase: Phase 2; Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Masking Description:

The Reading Center team and Sponsor were also masked.

Primary Purpose: Treatment

Condition

• Geographic Atrophy
• Macular Degeneration

Intervention

• Drug: Zimura
  Zimura 20 mg/mL solution for intravitreal (IVT) injection
  Other Name: avacincaptad pegol
• Other: Sham
  The Sham procedure included the blunt opening of an empty, needleless syringe barrel placed on the conjunctiva in the inferotemporal quadrant of the eyeball to simulate the pressure of an injection.

Study Arms

• Experimental: Zimura 1 mg [Part 1]
  Participants received 1 mg of Zimura in the study eye administered via IVT injection (50 µL) on Day 1 and monthly up to 18 months.
  Intervention: Drug: Zimura
• Experimental: Zimura 2 mg [Part 1]
  Participants received 2 mg of Zimura in the study eye administered via IVT injection (100 µL) on Day 1 and monthly up to 18 months.
  Intervention: Drug: Zimura
• Sham Comparator: Sham [Part 1]
  Participants received a Sham injection of an empty, needleless syringe administered in the study eye on Day 1 and monthly up to 18 months.
  Intervention: Other: Sham
• Experimental: Zimura 2 mg (Zimura 2mg+Sham) [Part 2]
  Participants received 2 mg of Zimura in the study eye administered via IVT injection (100 µL) and a subsequent Sham administration on Day 1 and monthly up to 18 months.
  Interventions:

  • Drug: Zimura
  • Other: Sham
• Experimental: Zimura 4 mg (Zimura 2mg+Zimura 2mg) [Part 2]
  Participants received 4 mg of Zimura in the study eye administered via two consecutive IVT injections (2 x 100 µL) on Day 1 and monthly up to 18 months.
  Intervention: Drug: Zimura
• Sham Comparator: Sham (Sham+Sham) [Part 2]
  Participants received two consecutive Sham injections of empty, needleless syringes administered in the study eye on Day 1 and monthly up to 18 months.
  Intervention: Other: Sham

• Publications *: Jaffe GJ, Westby K, Csaky KG, Mones J, Pearlman JA, Patel SS, Joondeph BC, Randolph J, Masonson H, Rezaei KA. C5 Inhibitor Avacincaptad Pegol for Geographic Atrophy Due to Age-Related Macular Degeneration: A Randomized Pivotal Phase 2/3 Trial. Ophthalmology. 2021 Apr;128(4):576-586. doi: 10.1016/j.ophtha.2020.08.027. Epub 2020 Sep 1.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 26, 2020): 286
• Original Estimated Enrollment (submitted: February 18, 2016): 300
• Actual Study Completion Date: April 23, 2020
• Actual Primary Completion Date: September 26, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Participants of either gender aged ≥ 50 years
• Diagnosis of Non-foveal GA secondary to dry AMD

Exclusion Criteria:

• Evidence of Choroidal Neovascularization (CNV)
• GA secondary to any condition other than AMD
• Any prior treatment for AMD or any prior intravitreal treatment for any indication in either eye, except oral supplements of vitamins and minerals
• Any intraocular surgery or thermal laser within three (3) months of trial entry
• Any prior thermal laser in the macular region, regardless of indication
• Any ocular or periocular infection in the twelve (12) weeks
• Previous therapeutic radiation in the region of the study eye
• Any sign of diabetic retinopathy in either eye

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 50 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: Croatia, Czechia, Estonia, Hungary, Israel, Latvia, United States

Administrative Information

• NCT Number: NCT02686658
• Other Study ID Numbers: OPH2003; 2015-003991-56 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

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: Astellas Pharma Inc ( IVERIC bio, Inc. )
• Original Responsible Party: Ophthotech Corporation
• Current Study Sponsor: IVERIC bio, Inc.
• Original Study Sponsor: Ophthotech Corporation
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Astellas Pharma Inc
• Verification Date: April 2023