A Study in Adults With Geographic Atrophy

Official title

A Phase 2, Multicentre, Randomised, Double-masked, Placebo-controlled, Parallel-group, Dose-range Finding Study, to Assess the Efficacy and Safety of Oral STL303 in Adults With Geographic Atrophy Secondary to Age-related Macular Degeneration

Overview

The purpose of this clinical research study is to look at how safe STL303 is and whether it works when given to people with Geographic Atrophy (GA) secondary to Age-related Macular Degeneration (AMD). Geographic atrophy secondary to AMD is a condition where cells in the back part of the eye slowly die, causing a blurry, or missing spot in the centre of vision.

Detailed description

This study is designed as a randomized, multi-center, double-masked, dose-range finding study to characterize the efficacy and safety of STL303.

Interventions

• Drug STL303
  STL303 arm participants will receive a specific dose of STL303
• Drug Placebo
  Placebo arm participants will receive placebo

Primary outcome measures

• Reduction of rate of total EZ area loss [Time frame: From baseline to Week 52]

Secondary outcome measures (8)

• Number of reported treatment-emergent adverse events (TEAE) and serious adverse events (SAEs) [Time frame: Baseline to week 108]
• Change in Retinal sensitivity [Time frame: From enrolment to end of treatment at week 104]
• Rate of disease progression (photoreceptor loss) [Time frame: From enrolment to end of treatment at week 104]
• Change in Vision-Related Quality of Life [Time frame: From Baseline to end of treatment at week 104]
• Maximum serum concertation at steady-state (Cmax, ss) of STL303 [Time frame: Weeks 0, 4, 12, 26, 52, 78, and 104 pre and 2 hours post dose.]
• Determine pharmacodynamic profile of STL 303 [Time frame: Weeks 0, 4, 12, 26, 52, 78 and 104 pre and 2 hours post dose.]
• Trough plasma concentration at steady-state of STL303 [Time frame: Weeks 0, 4, 12, 26, 52, 78, and 104 pre and 2 hours post dose.]
• Area under plasma concentration-time curve for STL303 [Time frame: Weeks 0, 4, 12, 26, 52, 78, and 104 pre and 2 hours post dose.]

Eligibility criteria

Inclusion criteria

The study eye must meet all inclusion criteria. If both eyes meet the inclusion criteria, the eye with the better visual acuity at the Screening visit will be designated as the study eye. If both eyes have the same visual acuity, the right eye will be selected as the study eye.

• Participants ≥60 years of age at the time of Screening (signing the ICF).
• Diagnosis of non-exudative AMD in both eyes, with confirmed presence of phenotypic hallmarks of AMD such as hard and/or soft drusen.
• The GA lesion in the study eye must meet the following criteria as determined by the central Reading Centre's assessment at Screening:

• Total GA area must be ≥2.5 and ≤10.16 mm2 (1 and 4 DA, respectively) as measured using SD-OCT.
• If GA is multifocal, at least one focal lesion must be ≥1.25 mm2 (0.5 DA), with the overall aggregate area of GA, as specified above in 3a.
• The entire GA lesion must be completely visualised on the 6 × 6 mm fovea-centred OCT scan and must be able to be imaged in its entirety and not contiguous with any areas of peripapillary atrophy.
• The entire EZ loss border must be completely visualised on the 6 × 6 mm fovea centred OCT scan as determined by the central Reading Centre's assessment at Screening; in cases where the EZ loss border is close to the grid boundary, a grid centred on the atrophic area may be used at the Baseline visit (as advised by the Reading Centre).
• All GA lesions must be at least 150 μm from foveal centre.
• Confirmed presence of any pattern of hyper-autofluorescence in the junctional zone of GA; absence of hyper-autofluorescence is exclusionary.
• BCVA by Early Treatment Diabetic Retinopathy Study (ETDRS) score of ≥55 letters (Snellen equivalent ≥20/70) in the study eye at the Screening visit and Baseline visit.
• Low luminance visual acuity (LLVA) by ETDRS score of ≥10 letters in the study eye at the Screening visit and Baseline visit.
• Meets the following criteria related to microperimetry:

• Able to detect fixation target.
• Fixation losses must be ≤20%.
• Participant is willing and able to undertake microperimetry assessment in the opinion of the Investigator.
• Able to take IMP or have an appropriate designee who can administer the IMP (i.e., a capable family member or caregiver).
• Able to provide written informed consent and willing to comply with all site visits, examinations, daily IMP administrations and dosing diary entries, and other conditions of the study protocol.
• Adequate clarity of ocular media, adequate pupillary dilation, and fixation to permit the collection of good quality images as determined by the Investigator.
• The fellow eye may have any of the following: AMD without GA, AMD with GA, or foveal GA (ongoing treatment with complement inhibitor therapies in the fellow eye is allowed).
• Vaccination against Neisseria meningitidis and Streptococcus pneumoniae infection are required at least two weeks prior to the start of the treatment with STL303.
• If not received previously, vaccination against Haemophilus influenzae type b infection should be given, if available and according to local regulations.
• Body mass index (BMI) ≥18 kg/m2 to ≤40 kg/m2.
• Participants of childbearing potential (POCBP) must use an appropriate birth control if not confirmed postmenopausal; male participants with partners of childbearing potential must agree to use highly effective contraception methods during the study and for 1 month after the last dose of the IMP.
• Participants must agree to refrain from donating gametes during the duration of the study and for 1 month after the last dose of the IMP.

Exclusion criteria

• Atrophic retinal disease of causality other than AMD including myopia-related maculopathy and macular dystrophies such as pattern dystrophy and Stargardt disease in either eye.
• Evidence of ongoing exudative AMD, polypoidal choroidal vasculopathy, or macular neovascularisation in either eye by history, OCT, fluorescein angiography (FA) or optical coherence tomography angiography (OCTA) as determined by the Reading Centre (prior IVT treatment for CNV is permitted in the fellow eye so long as the last injection was more than two years previously).
• Previous treatment with any ocular photodynamic therapy or laser coagulation to the macula in the study eye.
• Presence of active/current retinal vein occlusion in the study eye.
• Presence of vitreous haemorrhage in the study eye.
• History of retinal detachment in the study eye.
• Ocular conditions - either eye:

• Presence of at least moderate non-proliferative diabetic retinopathy (or worse) in either eye (a history of diabetes mellitus without retinopathy and mild non-proliferative diabetic retinopathy is not a criterion for exclusion).
• Presence of any other retinal pathology that, in the opinion of the Investigator, would confound the diagnosis or assessment of GA or would make follow-up not feasible.
• History of herpetic infection in either eye.
• Active uveitis and/or vitritis (grade trace or above) in either eye.
• History of idiopathic or autoimmune-associated uveitis in either eye.
• Active infectious conjunctivitis, keratitis, scleritis, or endophthalmitis in either eye.
• Spherical equivalent of the refractive error demonstrating >6 diopters of myopia or an axial length >26 mm in either eye.
• Intraocular surgery (including lens replacement surgery) within 3 months prior to randomisation in either eye.
• Yttrium Aluminium Garnet (YAG) laser in either eye within 1 month prior to randomisation.
• History of infection with Neisseria meningitidis, Streptococcus pneumoniae or Haemophilus influenzae type b despite vaccination.
• History or known human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV)-positivity (unless treated \[for HBV and HCV only\]) and achieved sustained viral response with negative polymerase chain reaction (PCR).
• Known ongoing immunodeficiency with or without treatment.
• Previous participation in a retinal gene therapy clinical study where the gene therapy was delivered to either eye.
• History of any prior IVT treatment for any indication other than AMD in either eye. Prior IVT treatment for CNV is permitted in the fellow eye so long as the last injection was more than two years previously.
• Any prior treatment for AMD in the study eye (for example, surgical, radiation, thermotherapeutic, or laser intervention), except oral supplements or minerals; prior treatment with Izervay or Syfovre is allowed in the study eye so long as 6 months have elapsed since the last treatment and so long as the participant did not experience any ocular inflammation or adverse events during the treatment with either Izervay or Syfovre. Ongoing treatment with Izervay or Syfovre is permitted in the fellow eye.
• Usage of systemic immunosuppressants or other immunomodulatory drugs within 90 days prior to the first administration or within 5 half-lives of the drug (whichever is longer), specifically including but not limited to cyclophosphamide, rituximab, infliximab, mycophenolate mofetil, cyclosporine, tacrolimus, sirolimus, systemic corticosteroids (inhaled or topical corticosteroids, or corticosteroids directly injected into the joints are allowed).
• Previous treatment with other systemic complement inhibitors within 30 days prior to the first dose, or within 5 half-lives of the drug, or within the potential period of residual effects from previous clinical studies, such as anti-sense oligonucleotide (ASO) or ribonucleic acid interference (RNAi), whichever is longer.
• Participants with any unstable or clinically significant medical condition that, in the opinion of the Investigator, could pose a risk of complications or interfere with participation during the course of the study.
• Participants with prolonged corrected QT interval (QTc) at Screening or at Baseline (QT interval corrected using Fridericia's formula \[QTcF\] >480 ms).
• Participants with clinically-relevant cardiac events within the last 2 years.
• Participants with significantly abnormal liver function at Screening or at Baseline: any parameter of ALT, AST, gamma glutamyl transferase (GGT) or alkaline phosphatase (ALP) >3 × upper limit of normal (ULN); serum bilirubin total >1.5 × ULN.
• Platelet count <75000 cells/mm3.
• Haemoglobin value <8 gm/dL.
• History of end stage liver or kidney disease requiring dialysis or transplant.
• History of hypersensitivity to any of the study treatments or excipients or to drugs of similar chemical classes or clinically relevant sensitivity to fluorescein dye as assessed by the Investigator.
• History of alcohol or drug abuse within the last 5 years.
• Ongoing treatment with cytochrome P450 2C8 (CYP2C8) inhibitors, or inducers or strong P-glycoprotein inhibitors.
• Ongoing participation in any other clinical study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 20 centers

• California Retina Consultants — Bakersfield
• Retina-Vitreous Associates Medical Group — Beverly Hills
• Kaiser Permanente - Oakland — Oakland
• Retina Specialists of Colorado — Aurora
• Retina Group of New England, PC — Waterford
• Retina Vitreous Associates of Florida — St. Petersburg
• Florida Retina Institute — Wildwood
• University Retina and Macula Associates, P.C. — Lemont
• … and 12 more centers

Argentina · 11 centers

• Buenos Aires Macula S.A — Buenos Aires
• Centro Medico Viamonte SRL — Buenos Aires
• Centro de Ojos Quilmes — Quilmes
• Hospital Britanico de Buenos Aires — Buenos Aires
• Instituoto Oftalmologico de Buenos Aires S.A. — Buenos Aires
• Centro Oftalmologico Dr. Charles S.A. — Buenos Aires
• Centro Privado de Ojos — Ciudad Autonoma Buenos Aires
• IMOC Instituto de Microcirugia Ocular Cordoba — Córdoba
• … and 3 more centers

Poland · 10 centers

• Szpital Swietego Lukasza S. A. — Bielsko-Biala
• Specjalistyczny Osrodek Okulistyczny Oculomedica — Bydgoszcz
• Prywatna Klinika Okulistyczna OFTALMIKA — Bydgoszcz
• Clinical Medical Research Sp. z o.o. — Katowice
• Specjalistyczna Praktyka Lekarska Prof. Edward Wylęgała — Katowice
• Centrum Medyczne Dietla 19 — Krakow
• Centrum Diagnostyki i Mikrochirurgii Oka LENS — Olsztyn
• Poznanskie Centrum Wzroku sp z o o — Poznan
• … and 2 more centers

Australia · 6 centers

• Sydney Eye Hospital — Sydney
• Sydney West Retina — Westmead
• Queensland Eye Institute — South Brisbane
• Adelaide Eye and Retina Centre — Adelaide
• Cerulea Pty Ltd — East Melbourne
• Royal Melbourne Hospital — Parkville

Switzerland · 6 centers

• Ente Ospedaliero Cantonale — Bellinzona
• Berner Augenklinik — Bern
• Augenarzte Bern Zentrum Marktgasse — Bern
• Vista Augenklinik Binningen — Binningen
• Swiss Visio Montchoisi — Lausanne
• Stadtspital Triemli — Zurich

United Kingdom · 4 centers

• The Retina Clinic London — London
• Southampton General Hospital — Southampton
• University Hospitals of Leicester NHS Trust — Leicester
• Royal Victoria Infirmary — Newcastle upon Tyne

Czechia · 3 centers

• OFTEX, s.r.o. — Pardubice
• Fakultni nemocnice Kralovske Vinohrady — Prague
• Axon Clinical s.r.o. — Prague

Identifiers

NCT: NCT07606365 · STL303-202

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗