Clinical trial NCT06541704: A Study Investigating Subcutaneously Administered Pozelimab in Combination With Cemdisiran or Cemdisiran Alone in Adult Participants With Geographic Atrophy
Official title: A Multicenter, Randomized, Double-Masked, Placebo-Controlled Phase 3 Study of the Efficacy, Safety, and Tolerability of Subcutaneously Administered Pozelimab in Combination With Cemdisiran or Cemdisiran Alone in Participants With Geographic Atrophy Secondary to Age-Related Macular Degeneration
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Age-related Macular Degeneration (AMD)
Geographic Atrophy (GA)
Keywords: GA secondary to AMD
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2024-08-07
Enrollment: 750
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is researching experimental (study) drugs called pozelimab and cemdisiran. The study is focused on participants who have geographic atrophy (GA) caused by age-related macular degeneration (AMD). Geographic atrophy is a medical term that refers to later-stage cases of AMD which is an eye condition affecting central vision (what one sees straight ahead).

The purpose of this study is to evaluate the progression rate of Geographic Atrophy in eyes of patients treated with cemdisiran alone or in combination with pozelimab compared to those treated with placebo.

The study is looking at several other research questions, including:

* What side effects may happen from taking the study drug(s)
* How much study drug(s) are in the blood at different times
* Whether the body makes antibodies against the study drug(s) (which could make the study drug(s) less effective or could lead to side effects)


Eligibility criteria: Key Inclusion Criteria:

1. Study eye with diagnosis of GA of the macula secondary to AMD not involving the foveal center point as described in the protocol
2. Total GA area in the study eye measuring between ≥2.5 mm2 and ≤17.5 mm2 as described in the protocol
3. BCVA of 35 letters or better using ETDRS charts (20/200 Snellen equivalent) in the study eye as described in the protocol
4. Sufficiently clear ocular media, adequate pupillary dilation and fixation to permit quality fundus imaging in the study eye as described in the protocol
5. Willing and able to comply with clinic visits and study-related procedures, including completion of the full series of meningococcal vaccinations and pneumococcal vaccination required per protocol

Key Exclusion Criteria:

1. GA in either eye due to causes other than AMD such as Stargardt disease, cone rod dystrophy or toxic maculopathies like hydroxychloroquine maculopathy
2. History or current evidence of macular neovascularization and/or exudation in either eye as described in the protocol
3. Prior or current Intravitreal (IVT) treatment of any kind for any indication in study eye or fellow eye, except approved or investigational IVT complement inhibitor therapy as long as last dose was ≥6 months prior to randomization
4. Prior intraocular surgery except cataract extraction or minimally invasive glaucoma surgery in study eye as long as date of these procedures was ≥3 months prior to randomization
5. Comorbid progressive ocular condition (eg, diabetic retinopathy, macular edema, uncontrolled glaucoma, full thickness macular hole) in study eye that could affect central vision and confound study
6. Any ophthalmologic condition that reduces the clarity of the media and that, in the opinion of the investigator interferes with ophthalmologic examination of the study eye (e.g., advanced cataract or corneal abnormalities) as described in the protocol

   Systemic Exclusion criteria
7. History or current use of systemic complement inhibitor therapy within 6 months prior to randomization as described in the protocol
8. History of solid organ or bone marrow transplantation
9. Use of chronic (\>14 days) systemic corticosteroids (oral or parenteral, ≥20 mg oral prednisone or equivalent) within the previous 30 days prior to the first screening visit as described in the protocol
10. Current or prior use of systemic immunosuppressive therapy other than corticosteroids or the likelihood of treatment with any such agent during the study inclusive of the screening period
11. Not meeting meningococcal or pneumococcal vaccination requirements as described in the protocol
12. Carrier of Neisseria meningitidis based on culture collected during screening
13. Has a hemoglobin A1C ≥ 8.0% during screening as described in the protocol

NOTE: Other protocol-defined Inclusion/ Exclusion Criteria apply

Primary outcomes:
measure: Growth rate (slope) of total GA lesion area (mm2 /year) measured by Fundus autofluorescence (FAF)
timeFrame: From baseline to week 52
Secondary outcomes:
measure: Loss of Best corrected visual acuity (BCVA) ≥15 Early treatment diabetic retinopathy study (ETDRS) letters at any 2 consecutive study visits
timeFrame: From baseline through week 52 and week 104
measure: Change in Low-contrast quantitative visual acuity (LC-qVA)
timeFrame: From baseline to week 52 and week 104
measure: Change in Low-luminance low-contrast quantitative visual acuity (LL-LC-qVA)
timeFrame: From baseline to week 52 and week 104
measure: Change in Quantitative contrast sensitivity function (qCSF)
timeFrame: From baseline to week 52 and week 104
measure: Growth rate (slope) of total GA lesion area (mm2 /year) measured by FAF
timeFrame: From baseline to week 104
measure: Concentrations of total pozelimab in serum
timeFrame: Through week 52 and week 104
measure: Concentrations of total cemdisiran in plasma
timeFrame: Through week 52 and week 104
measure: Change in concentration of total Complement component 5 (C5)
timeFrame: From baseline to week 52 and week 104
measure: Incidence of Antidrug antibody (ADA) to pozelimab
timeFrame: Through week 52 and week 104
measure: Titer of ADA to pozelimab
timeFrame: Through week 52 and week 104
measure: Incidence of ADA to cemdisiran
timeFrame: Through week 52 and week 104
measure: Titer of ADA to cemdisiran
timeFrame: Through week 52 and week 104
measure: Incidence of Neutralizing antibody (NAb) to pozelimab
timeFrame: Through week 52 and week 104
measure: Occurrence of Treatment-emergent adverse events (TEAEs)
timeFrame: Through week 52, 104 and week 284
measure: Severity of TEAEs
timeFrame: Through week 52, 104 and week 284
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Associated Retina Consultants
state: Arizona
city: Beverly Hills
country: United States
facility: Retina Vitreous Associates Medical Group
state: California
city: Encino
country: United States
facility: The Retina Partners
state: California
city: Fullerton
country: United States
facility: Retina Consultants of Orange County
state: California
city: Huntington Beach
country: United States
facility: Salehi Retina Institute dba Retina Associates of Southern California
state: California
city: Long Beach
country: United States
facility: South Coast Retina Center
state: California
city: Los Angeles
country: United States
facility: American Institute of Research
state: California
city: Modesto
country: United States
facility: Retinal Consultants Medical Group Inc Modesto
state: California
city: Oxnard
country: United States
facility: California Retina Consultants
state: California
city: Pasadena
country: United States
facility: California Eye Specialists Medical Group Inc.
state: California
city: Poway
country: United States
facility: Retina Consultants San Diego
state: California
city: Sacramento
country: United States
facility: Vrmg Inc
state: California
city: Sacramento
country: United States
facility: Retinal Consultants Medical Group (RCMG) - Greenback Lane Retina Center
state: California
city: Torrance
country: United States
facility: Macula Retina Vitreous Research Institute
state: California
city: Colorado Springs
country: United States
facility: Retina Consultants of Southern Colorado
state: Colorado
city: Durango
country: United States
facility: Southwest Retina Research Center
state: Colorado
city: Lakewood
country: United States
facility: Colorado Retina - Lakewood
state: Colorado
city: Longmont
country: United States
facility: Eye care Center of Northern Colorado doing business as Advanced Vision Research Institute
state: Colorado
city: Waterford
country: United States
facility: Retina Group of New England
state: Connecticut
city: Coral Springs
country: United States
facility: Advanced Research
state: Florida
city: Fort Lauderdale
country: United States
facility: Retina Group of Florida
state: Florida
city: Fort Myers
country: United States
facility: National Ophthalmic Research Institute
state: Florida
city: Jacksonville
country: United States
facility: Florida Retina Institute, Jacksonville Perimeter Park- Ophthalmology
state: Florida
city: Orlando
country: United States
facility: Florida Retina Institute - Orlando
state: Florida
city: Saint Petersburg
country: United States
facility: Retina Vitreous Associates of Florida Saint Petersburg
state: Florida
city: Sarasota
country: United States
facility: Retina Group of Florida, RAS-Sarasota Retina Center-Ophthalmology
state: Florida
city: Augusta
country: United States
facility: Southeast Retina Center
state: Georgia
city: Marietta
country: United States
facility: Georgia Retina - Marietta
state: Georgia
city: Chicago
country: United States
facility: The University of Chicago
state: Illinois
city: Lemont
country: United States
facility: University Retina and Macula Associates PC - Lemont
state: Illinois
city: Oak Park
country: United States
facility: Illinois Retina Associates
state: Illinois
city: Metairie
country: United States
facility: Ross Davis Retina
state: Louisiana
city: West Monroe
country: United States
facility: Eye Assoc. of NE LA dba Haik Humble Eye Ctr
state: Louisiana
city: West Monroe
country: United States
facility: Eye Associates of Northeast Louisiana dba Haik Humble Eye Center
state: Louisiana
city: Hagerstown
country: United States
facility: Mid Atlantic Retina Specialist
state: Maryland
city: Hagerstown
country: United States
facility: Cumberland Valley Retina Consultants-Ophthalmology
state: Maryland
city: Boston
country: United States
facility: Opthalmic Consultants of Boston
state: Massachusetts
city: Madison
country: United States
facility: Mississippi Retina Associates
state: Mississippi
city: Saint Louis
country: United States
facility: Retina Research Institute, LLC
state: Missouri
city: Liverpool
country: United States
facility: Retina Vitreous Surgeons of Central New York, PC
state: New York
city: Asheville
country: United States
facility: Western Carolina Retinal Associates
state: North Carolina
city: Hickory
country: United States
facility: Graystone Eye
state: North Carolina
city: Winston-Salem
country: United States
facility: Piedmont Retina Specialist
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Eye Institute
state: Ohio
city: Dublin
country: United States
facility: Midwest Retina, Inc
state: Ohio
city: Edmond
country: United States
facility: Retina Vitreous Center - Edmond
state: Oklahoma
city: Tulsa
country: United States
facility: Tulsa Retina Consultants
state: Oklahoma
city: Eugene
country: United States
facility: Verum Research LLC
state: Oregon
city: Portland
country: United States
facility: Retina Northwest
state: Oregon
city: Portland
country: United States
facility: EyeHealth Northwest
state: Oregon
city: Springfield
country: United States
facility: Cascade Medical Research Institute LLC
state: Oregon
city: Erie
country: United States
facility: Erie Retinal Surgery & Erie Retina Research
state: Pennsylvania
city: Sewickley
country: United States
facility: Sewickley Eye Group
state: Pennsylvania
city: Greenville
country: United States
facility: Retina Consultants of Carolina
state: South Carolina
city: Ladson
country: United States
facility: Charleston Neuroscience Institute LLC
state: South Carolina
city: Mount Pleasant
country: United States
facility: Charleston Neuroscience Institute, LLC
state: South Carolina
city: West Columbia
country: United States
facility: Palmetto Retina Center
state: South Carolina
city: Nashville
country: United States
facility: Tennessee Retina, PC
state: Tennessee
city: Austin
country: United States
facility: Austin Research Center for Retina
state: Texas
city: Austin
country: United States
facility: Austin Retina Associates
state: Texas
city: Bellaire
country: United States
facility: Retina Consultants Texas
state: Texas
city: Burleson
country: United States
facility: Star Retina PLLC
state: Texas
city: Dallas
country: United States
facility: Red River Research Partners (Formerly AXIS Clinical)
state: Texas
city: Dallas
country: United States
facility: Texas Retina Associates
state: Texas
city: Katy
country: United States
facility: Retina Consultants of Texas
state: Texas
city: McAllen
country: United States
facility: Valley Retina Institute, P.A.
state: Texas
city: Round Rock
country: United States
facility: Austin Retina Associates
state: Texas
city: San Antonio
country: United States
facility: Retina Associates of South Texas
state: Texas
city: San Antonio
country: United States
facility: Retina Consultants of Texas
state: Texas
city: San Antonio
country: United States
facility: Retina Consultants of Texas Brown Retina Institute
state: Texas
city: Southlake
country: United States
facility: Retina Center of Texas
state: Texas
city: The Woodlands
country: United States
facility: Retina Consultants Texas
state: Texas
city: Salt Lake City
country: United States
facility: Retina Associates Of Utah Retina Specialist
state: Utah
city: Lynchburg
country: United States
facility: Piedmont Eye Center
state: Virginia
city: Richmond
country: United States
facility: Virginia Eye Institute
state: Virginia
city: Vienna
country: Austria
facility: VIROS - Vienna Institute for Research in Ocular Surgery
city: Ottawa
country: Canada
facility: Retina Centre of Ottawa - Department of Ophthalmology
state: Ontario
city: Munster
country: Germany
facility: St. Franziskus-Hospital
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: