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An ischaemia modulator has demonstrated it is safe and well tolerated in a Phase 1/2a trial in diabetic macular ischaemia patients.
Reviewed by Dr Quan Dong Nguyen.
A recent Phase 1/2a trial of an intravitreal treatment designed to treat diabetic macular ischaemia (DMI), BI-X (Boehringer Ingelheim), found the candidate to be well tolerated with no dose-limiting events and no drug-related adverse events, according to Dr Quan Dong Nguyen, a professor of ophthalmology at Byers Eye Institute at Stanford University School of Medicine in Palo Alto, California, United States.
DMI is defined as any disruption in retinal vascularity within the superficial and/or deep retinal plexus as seen on optical coherence tomography angiography, and it is a complication of diabetic retinopathy (DR). Currently, there is no treatment available that can prevent or stop progression of DMI. Dr Nguyen pointed out that the development of a treatment is important because it is a common complication that can have a profound impact on a patient’s vision.
BI-X works as an anti-ischaemia modulator of the human protein, semaphorin 3A, which blocks revascularisation in ischaemic retinas.
DMI patients enrolled in the Phase 1/2a study had previously been treated with laser for DR. The study has two parts, or ‘phases’, and all subjects treated with BI-X have received one intravitreal dose of the drug.
The non-randomised, open-label section of the study is complete. Three cohorts received 0.5-, 1- or 2.5-mg doses of the therapy; the cohorts included three, three and six subjects, respectively. The primary endpoint was the number of dose-limiting events, and the secondary endpoints were the numbers of drug-related and ocular adverse events.
According to Dr Nguyen, the best-corrected visual acuity (BCVA) improved slightly compared with baseline in the subjects assigned to 1 and 2.5 mg of BI-X. No dose-limiting, drug-related or serious adverse events occurred. Three subjects experienced ocular adverse events: specifically, subconjunctival haemorrhage and ocular hyperaemia, both in the 0.5-mg cohort.
One vitreous detachment occurred in the 2.5-mg cohort. Four procedural-related adverse events occurred: subconjunctival haemorrhage, ocular hyperaemia and temporary intraocular pressure increase in the 0.5-mg group, and mild pain after the procedure in the 2.5-mg group.
The findings in the three cohorts were similar. The main take-aways from the SRD study were that BI-X was well tolerated by subjects with DMI in all three dosing cohorts and that the BCVA showed signs of improvement compared with baseline in the 1- and 2.5-mg cohorts.
In the second, ongoing, single masked and randomised segment of the study, the BI-X cohort (20 subjects) will receive three 2- to 5-mg doses separated by 4-week intervals and 10 subjects are to receive sham injections.
The primary endpoint is the number of drug-related adverse events; the secondary endpoints are the number of ocular adverse events and the changes from baseline in the foveal avascular area size, BCVA and central retinal thickness.
“Discovering a treatment for DMI is a major challenge for many clinician-scientists, as DMI can lead to significant visual loss, even if the diabetic macular oedema is well controlled,” Dr Nguyen concluded. “It is our hope that BI-X can be among the first successful treatments for this devastating complication of diabetic retinopathy.”