South Asian Patients With Diabetic Macular Oedema Treated With Faricimab Assessing the Efficacy, Durability, and Safety (SEAFAR Study)
Trial Snapshot
- Phase
- Phase 4
- Status
- Not yet recruiting
- Sponsor
- Enrollment
- 120
- Primary Endpoint
- Change From Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye
Study Overview
Brief Summary
The YOSEMITE and RHINE trials, which studied DMO treated with faricimab, had a majority Caucasian cohort, and the small Asian cohort was East Asian, with no South Asian representation. South Asians have a much higher prevalence of diabetes and its ophthalmic complication of DMO.
The SEAFAR study is designed to address this unmet need by specifically evaluating faricimab in a UK-based South Asian cohort with diabetic macular oedema (DMO), delivered via a pragmatic treat-and-extend regimen, for clinically meaningful visual acuity gains, durable anatomic control of DMO, and an acceptable safety profile at week 88 in South Asian patients, with interim benefits by week 52.
Detailed Description
Diabetic macular oedema (DMO), characterised by accumulation of extracellular fluid in the macula due to breakdown of the blood-retinal barrier, is the most common cause of sight-threatening diabetic retinopathy. It affects approximately one in fifteen people with diabetes, corresponding to more than 20 million individuals worldwide, and is a leading cause of vision impairment. The risk of diabetes is not equally distributed across populations. In the UK, individuals of South Asian heritage (Indian, Pakistani, Bangladeshi, Sri Lankan) have a 2-4 times higher risk of developing type 2 diabetes compared to those of European ancestry, with onset often at a younger age and at lower body mass index (BMI) thresholds. They are also shown to have a higher prevalence of retinopathy and maculopathy compared with White Europeans, with worse systemic risk factors (such as HbA1c, blood pressure, cholesterol). Despite this, there is limited trial-based evidence addressing treatment outcomes for these high-risk groups.
Anti-vascular endothelial growth factor (anti-VEGF) therapy has transformed the management of DMO. Pivotal trials such as RISE/RIDE and VIVID/VISTA established the efficacy of ranibizumab and aflibercept in improving visual outcomes and reducing retinal thickness. More recently, faricimab, a bispecific antibody targeting VEGF-A and Angiopoietin-2, has demonstrated efficacy with the potential for extended durability. In the YOSEMITE and RHINE trials, faricimab provided comparable or superior visual and anatomical outcomes to aflibercept 2mg, with a substantial proportion of patients achieving treatment intervals of up to every 16 weeks.
While YOSEMITE and RHINE enrolled over 1,800 patients, the majority of them were non-Asian (n=1747 versus n=144 for Asians). Subgroup analyses for participants in YOSEMITE and RHINE from Asian countries demonstrated broadly similar outcomes between Asian and non-Asian groups. However, the Asian participants were predominantly from East Asia (China, Japan, Korea, Singapore, Taiwan), which means that these findings cannot be extrapolated to South Asian patients given their potentially distinct genetic, biological, and lifestyle risk profiles. Notably, the ELEVATUM trial, designed to evaluate faricimab in underrepresented groups (African-Caribbean, Hispanic, Pacific Islander), similarly did not include adequate representation of South Asians. Thus, a critical evidence gap remains.
The SEAFAR study is designed to address this unmet need by specifically evaluating faricimab in a UK-based South Asian cohort with DMO. The rationale is threefold:
- Scientific need: Ethnic differences in disease prevalence, risk factor profiles and possibly treatment response necessitate focused evaluation. Biological differences in angiogenic pathways and systemic disease burden may influence treatment durability and safety.
- Clinical relevance: In the 2021 Census data by the UK government, 5.5 million people in England and Wales were from Asian ethnic groups - 1.9 million of these identified with the Indian ethnic group, with 1.6 million from the Pakistani ethnic group.
- Health system impact: If faricimab demonstrates similar or greater durability in South Asians, this could substantially reduce injection frequency and clinic visits. This is particularly relevant in communities with higher disease burden and in a National Health Service (NHS) setting where service capacity is constrained.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •All subjects must meet all of the following inclusion criteria to participate:
- •Patients who self-identify themselves as of South Asian origin. Including Indian, Pakistani, Bangladeshi and Sri Lankan.
- •Adults aged ≥18 years at time of consent.
- •Documented diagnosis of type 1 or type 2 diabetes mellitus.
- •Best-corrected visual acuity (BCVA) of 20-73 ETDRS letters, corresponding approximately to 6/12 to 6/120 Snellen (metres) in the study eye.
- •Centre-involving diabetic macular oedema (DMO) confirmed on SD-OCT, with a central subfield thickness (CST) ≥400 µm, in line with UK NICE guidance in the treatment naïve patients (75% of the cohort). 25% of cohort is previously treated DMO where treatment commenced within 3 years of the screening visit and responded to the anti VEGF, reviewed during this period and developed any clinically significant recurrence of DMO, with vision at least 6/18 or better in the enrolled eye.
- •Decreased visual acuity attributable primarily to DMO.
- •Both eyes may be eligible; however, the eye with the higher CST will be designated as the study eye.
- •Male or female participants are eligible. Women of childbearing potential must agree to remain abstinent or use highly effective contraception during the study and for at least 3 months after the final dose.
- •Ability and willingness to provide written informed consent and comply with all study procedures and follow-up.
Exclusion Criteria
- •All subjects meeting any of the following exclusion criteria at baseline will be excluded from participation:
- •Untreated diabetes mellitus, or initiation of oral or injectable anti-diabetic therapy within 3 months prior to Day
- •Uncontrolled blood pressure: systolic >180 mmHg or diastolic >100 mmHg at rest.
- •Pregnant or breastfeeding women, or intention to become pregnant during the study period.
- •Pan retinal photocoagulation (PRP) or macular laser in the study eye within 3 months prior to Day
- •Intraocular or periocular corticosteroid therapy in the study eye within 6 months prior to Day
- •Previous treatment with Fluocinolone acetonide (Iluvien) in the study eye.
- •Active proliferative diabetic retinopathy in the study eye.
- •Active ocular or periocular infection, or active intraocular inflammation, in the study eye.
- •Any ocular condition that could confound macular assessment or contribute to irreversible vision loss in the study eye, including:
- •Retinal vein occlusion
- •Significant epiretinal membrane
- •Tractional retinal detachment involving the posterior pole
- •Macular atrophy
- •Foveal scarring
- •Previous vitrectomy in the study eye.
- •Cataract surgery or any other intraocular surgery in the study eye within 3 months of baseline if followed by macular oedema which can confound the DMO diagnosis. Planned cataract surgery in the study eye once treatment commenced and after the loading dose, is allowed as per clinician discretion.
- •Known hypersensitivity to faricimab or any of its excipients.
- •Any systemic condition, abnormal laboratory finding, or concomitant therapy that, in the opinion of the investigator, may compromise patient safety or the validity of study results.
Arms & Interventions
single arm DMO treated with Faricimab
Intervention: Intravitreal anti-VEGF injection, Faricimab (Drug)
Outcomes
Primary Outcomes
Change From Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye
Time Frame: Baseline and Week 88 (+/- 14 days)
Change from baseline in best corrected visual acuity in the study eye, measured as ETDRS letter score.
Secondary Outcomes
- Distribution of Maximum Dosing Interval Achieved(Baseline through Week 88 (+/- 14 days), with interim assessment at Week 52 (+/- 14 days))
- Change From Baseline in Central Subfield Thickness (CST)(Baseline, Week 52 (+/- 14 days) and Week 88 (+/- 14 days))
- Proportion of Participants With Absence of Diabetic Macular Oedema(Week 52 (+/- 14 days) and Week 88 (+/- 14 days))
- Proportion of Participants With Absence of Intraretinal Fluid(Week 52 (+/- 14 days) and Week 88 (+/- 14 days))
- Proportion of Participants Gaining >=5, >=10 and >=15 ETDRS Letters From Baseline(Baseline, Week 52 (+/- 14 days) and Week 88 (+/- 14 days))
- Proportion of Participants Losing >=5, >=10 and >=15 ETDRS Letters From Baseline(Baseline, Week 52 (+/- 14 days) and Week 88 (+/- 14 days))
- Change From Baseline in Vision-Related Quality of Life (NEI VFQ-25)(Baseline, Week 52 (+/- 14 days) and Week 88 (+/- 14 days))
- Change From Baseline in Health-Related Quality of Life (EQ-5D)(Baseline, Week 52 (+/- 14 days) and Week 88 (+/- 14 days))
- Proportion of Participants With a 2-Step or 3-Step Improvement in Diabetic Retinopathy Severity Score (DRSS) From Baseline(Baseline, Week 52 (+/- 14 days) and Week 88 (+/- 14 days))
- Number of Participants With Ocular Adverse Events(Baseline through Week 88 (+/- 14 days), with interim assessment at Week 52 (+/- 14 days))
- Number of Participants With Systemic Adverse Events(Baseline through Week 88 (+/- 14 days), with interim assessment at Week 52 (+/- 14 days))
- Number of Participants With Serious Adverse Events (SAEs)(Baseline through Week 88 (+/- 14 days), with interim assessment at Week 52 (+/- 14 days))
- Number of Participants With Suspected Unexpected Serious Adverse Reactions (SUSARs)(Baseline through Week 88 (+/- 14 days), with interim assessment at Week 52 (+/- 14 days))