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NCT Number: NCT06541704

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

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)

Recruiting

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Key information

Age range

50 year–85 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Medical University Graz, Graz, Styria, Austria

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Key Inclusion Criteria:

  • Study eye with diagnosis of GA of the macula secondary to AMD as described in the protocol
  • Total GA area in the study eye measuring between ≥2.5 mm^2 and ≤17.5 mm^2 as described in the protocol
  • BCVA of 55 letters or better using ETDRS charts (20/80 Snellen equivalent) in the study eye as described in the protocol
  • Sufficiently clear ocular media, adequate pupillary dilation and fixation to permit quality fundus imaging in the study eye as described in the protocol
  • 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:

  • GA in either eye due to causes other than AMD, such as Stargardt disease, cone rod dystrophy or toxic maculopathies like hydroxychloroquine maculopathy
  • History or current evidence of Macular Neovascularization (MNV) and/or exudation or Peripapillary Choroidal Neovascularization (PPCNV) in either eye as described in the protocol
  • 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
  • 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
  • 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
  • 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

  • History or current use of systemic complement inhibitor therapy within 6 months prior to randomization as described in the protocol
  • History of solid organ or bone marrow transplantation
  • 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
  • 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
  • Not meeting meningococcal or pneumococcal vaccination requirements as described in the protocol
  • Carrier of Neisseria meningitidis based on culture collected during screening
  • Has a hemoglobin A1C ≥ 8.0% during screening as described in the protocol

NOTE: Other protocol-defined Inclusion/ Exclusion Criteria apply

Treatment and study plan

Pozelimab

Drug

Subcutaneous (SC) injection

Other names: REGN3918

Cemdisiran

Drug

SC injection

Other names: ALN-CC5

Placebo

Drug

SC injection

Primary outcomes

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

    Time frame: To week 52

Secondary outcomes

  1. Loss of Best Corrected Visual Acuity (BCVA) ≥15 letters [Early Treatment Diabetic Retinopathy Study (ETDRS)] from baseline

    Time frame: At week 52 and week 104

  2. Change from baseline in Low-Contrast quantitative Visual Acuity (LC-qVA)

    Time frame: At week 52 and week 104

  3. Change from baseline in Low-Luminance Low-Contrast quantitative Visual Acuity (LL-LC-qVA)

    Time frame: At week 52 and week 104

  4. Change from baseline in quantitative Contrast Sensitivity Function (qCSF)

    Time frame: At week 52 and week 104

  5. Growth rate (slope) of total GA lesion area (mm^2 /year) from baseline measured by FAF

    Time frame: To week 104

  6. Concentrations of total pozelimab in serum

    Time frame: Through week 52 and through week 104

  7. Concentrations of total cemdisiran in plasma

    Time frame: Through week 52 and through week 104

  8. Change from baseline in concentration of total Complement component 5 (C5)

    Time frame: Through week 52 and through week 104

  9. Incidence of Antidrug antibody (ADA) to pozelimab

    Time frame: Through week 52 and through week 104

  10. Magnitude of ADA to pozelimab

    Time frame: Through week 52 and through week 104

  11. Incidence of ADA to cemdisiran

    Time frame: Through week 52 and through week 104

  12. Magnitude of ADA to cemdisiran

    Time frame: Through week 52 and through week 104

  13. Incidence of Neutralizing Antibody (NAb) to pozelimab

    Time frame: Through week 52 and through week 104

  14. Occurrence of Treatment-Emergent Adverse Events (TEAEs)

    Time frame: Through week 52, 104, 140 and week 296

  15. Severity of TEAEs

    Time frame: Through week 52, 104, 140 and week 296

Study contacts

Contact information is provided by the study sponsor or research team.

Clinical Trials Administrator

CONTACT

[email protected]

844-734-6643

Sponsors and collaborators

Lead sponsor

Regeneron Pharmaceuticals

Industry

Registry information

Official study 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

Acronym: SIENNA

Important dates

Study start
2024
Primary completion
2027
Study completion
2032
First posted
Aug 7, 2024
Registry last updated
Jul 9, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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