A study Investigating Subcutaneously Administered Pozelimab in Combination with Cemdisiran or Cemdisiran Alone in Adult Participants with Geographic Atrophy

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Regeneron Pharmaceuticals Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Eye Diseases [C11]

Trial duration

22 May 2025 → ongoing

Decision date (initial)

2025-02-23

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2023-509547-27-00

ClinicalTrials.gov

NCT06541704

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Safety, Pharmacokinetic, Efficacy

To evaluate the effect of systemic Complement Component 5 (C5) inhibition on Geographic atrophy (GA) lesion growth over 52 weeks

Secondary objectives 5

1. To evaluate the effect of systemic C5 inhibition on functional measures of GA disease progression
2. To evaluate the effect of systemic C5 inhibition on GA lesion growth over 104 weeks
3. To assess the concentrations of total pozelimab in serum and total C5 and cemdisiran in plasma
4. To assess immunogenicity of pozelimab and cemdisiran
5. To assess the safety of pozelimab + cemdisiran combination therapy and cemdisiran monotherapy

Conditions and MedDRA coding

Geographic Atrophy Secondary to Age-Related Macular Degeneration

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Study eye with diagnosis of GA of the macula secondary to AMD as described in the protocol
2. Total GA area in the study eye measuring between ≥2.5 mm^2 and ≤17.5 mm^2 as described in the protocol
3. BCVA of 55 letters or better using ETDRS charts (20/80 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

Exclusion criteria 14

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 (MNV) and/or exudation or Peripapillary Choroidal Neovascularization (PPCNV) 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 or anti-VEGF 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
7. Systemic Exclusion criteria: History or current use of systemic complement inhibitor therapy within 6 months prior to randomization as described in the protocol
8. Systemic Exclusion criteria: History of solid organ or bone marrow transplantation
9. Systemic Exclusion criteria: 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. Systemic Exclusion criteria: Current or prior use of systemic immunosuppressive therapy other than corticosteroids within 12 months prior to randomization or the likelihood of treatment with any such agent during the study inclusive of the screening period as described in the protocol
11. Systemic Exclusion criteria: Not meeting meningococcal or pneumococcal vaccination requirements as described in the protocol
12. Systemic Exclusion criteria: Carrier of Neisseria meningitidis based on culture collected during screening
13. Systemic Exclusion criteria: Has a hemoglobin A1C ≥ 8.0% during screening as described in the protocol
14. Note: Other protocol-defined Inclusion/ Exclusion Criteria apply

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Growth rate (slope) of total GA lesion area (mm^2 /year) measured by Fundus Autofluorescence (FAF)

Secondary endpoints 15

1. Loss of Best Corrected Visual Acuity (BCVA) ≥15 Early Treatment Diabetic Retinopathy Study (ETDRS)
2. Change in Low-contrast quantitative Visual Acuity (LC-qVA)
3. Change in Low-Luminance Low-Contrast quantitative Visual Acuity (LL-LC-qVA)
4. Change in quantitative Contrast Sensitivity Function (qCSF)
5. Growth rate (slope) of total GA lesion area (mm^2 /year) measured by FAF
6. Concentrations of total pozelimab in serum
7. Concentrations of total cemdisiran in plasma
8. Change in concentration of total Complement component 5 (C5)
9. Incidence of Antidrug antibody (ADA) to pozelimab
10. Magnitude of ADA to pozelimab
11. Incidence of ADA to cemdisiran
12. Magnitude of ADA to cemdisiran
13. Incidence of Neutralizing antibody (NAb) to pozelimab
14. Occurrence of Treatment-emergent adverse events (TEAEs)
15. Severity of TEAEs

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Regeneron Pharmaceuticals Inc.

Sponsor organisation

Regeneron Pharmaceuticals Inc.

Address

777 Old Saw Mill River Road

City

Tarrytown

Postcode

10591-6717

Country

United States

Scientific contact point

Organisation

Regeneron Pharmaceuticals Inc.

Contact name

Clinical Trial Information

Public contact point

Organisation

Regeneron Pharmaceuticals Inc.

Contact name

Clinical Trial Information

Third parties 12

Locations

7 EU/EEA countries · 73 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Corrective measures 1 · Art. 77 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 68 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications