A Study Investigating Subcutaneously Administered Pozelimab in Combination With Cemdisiran or Cemdisiran Alone in Adult Participants With Geographic Atrophy (SIENNA)

Regeneron Pharmaceuticals

Status and phase: Enrolling; Phase 3

Conditions: Age-related Macular Degeneration (AMD); Geographic Atrophy (GA)

Treatments: Drug: Placebo; Drug: Pozelimab; Drug: Cemdisiran

Study type: Interventional

Funder types: Industry

Identifiers

NCT06541704

R3918-AMD-2326

2023-509547-27-00 (Registry Identifier)

Details and patient eligibility

About

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)

Enrollment: 750 estimated patients

Sex: All

Ages: 50+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

750 participants in 3 patient groups, including a placebo group

Pozelimab + Cemdisiran treatment group

Experimental group

Description:

Randomized 1:1:1

Treatment:

Drug: Cemdisiran

Drug: Pozelimab

Cemdisiran monotherapy treatment group

Experimental group

Description:

Randomized 1:1:1

Treatment:

Drug: Cemdisiran

Placebo treatment group

Placebo Comparator group

Description:

Randomized 1:1:1

Treatment:

Drug: Placebo