According to the company, THR-149 is currently being evaluated in the KALAHARI Phase 2, Part B clinical trial as a potential treatment for patients who respond suboptimally to anti-VEGF, the standard of care for treatment of DME.
Oxurion NV announced today that it has reached its enrollment target of 108 patients randomized in its KALAHARI Phase 2, Part B (NCT04527107) clinical trial for diabetic macular edema (DME).
According to the company, its investigators have successfully enrolled the 108 patients planned for this trial. Given the high level of interest from both investigators and patients, additional patients are still likely to be included in the trial, which would mean the trial will be over-enrolled.
As it has now reached its enrollment target, Oxurion confirms its previous guidance that it anticipates reporting top-line data from the KALAHARI trial in the fourth quarter of 2023.
Andy De Deene, MD, MBA, chief development officer of Oxurion, said the company was pleased to reach the target in the KALAHARI trial.
“The fact that we are likely to over-enroll is further testament to both the need for this therapy as well as the continued support of our investigators worldwide,” De Deene said in the news release. “The outcome of this trial, which is evaluating THR-149 for the treatment of DME against the current standard of care, aflibercept, could, if positive, provide an important alternative for the up to 50% of patients with DME who respond suboptimally to current anti-VEGF therapies.”
Tom Graney, CFA, CEO of Oxurion, pointed out that attaining this milestone is an important catalyst for Oxurion as the company moves towards completion of the KALAHARI trial.
“With the enrollment target reached, the study is well-positioned to report top-line results by the end of the year,” he said in the news release. “If positive, these results could provide a meaningfully better alternative for the millions of patients worldwide suffering from DME for whom current treatments are not effective.”
The company noted in a news release THR-149 is a bicyclic peptide that selectively inhibits human plasma kallikrein (PKal) with an inhibition constant of 0.22 nM. Through the inhibition of the kallikrein-kinin system (KKS), THR-149 prevents the induction of retinal vascular permeability, neurodegeneration, and inflammation.
THR-149 is currently being evaluated in the KALAHARI Phase 2, Part B clinical trial as a potential treatment for patients who respond suboptimally to anti-VEGF the standard of care for treatment of DME.
According to the company, the KALAHARI trial is evaluating Oxurion’s novel plasma kallikrein (PKal) inhibitor THR-149 as a potential treatment for DME patients who respond suboptimally to anti-VEGF therapy, the current standard of care. This milestone follows the recommendation from an Independent Data Monitoring Committee (IDMC) in December 2022 that the KALAHARI trial should continue based on the outcome of a pre-specified futility analysis that included an evaluation of interim efficacy and safety data from 31 patients at the three-month time point.
VEGF the standard of care for treatment of DME.
KALAHARI Phase 2, Part B
The Phase 2 KALAHARI trial is a two-part, randomized, prospective, multi-center trial assessing multiple (3) injections of THR-149 in DME patients. Part B is double-masked and actively controlled, with the high dose of THR-149 having been selected from Part A of the trial. Part B of the trial is enrolling approximately 108 patients who have previously shown a suboptimal response to anti-VEGF therapy, and where THR-149 is being evaluated against aflibercept, the current standard of care, as the active comparator.
KALAHARI Phase 2, Part A
Part A of the KALAHARI trial demonstrated that all dose levels of THR-149 had a favorable safety profile. All adverse events in the study eye were mild to moderate in intensity and no severe ocular adverse events were reported and no inflammation was observed. High-level data from Part A of the KALAHARI trial was first presented in October 2021, which demonstrated that the eight patients who received the highest dose of THR-149 achieved a mean BCVA gain of 6.1 letters at Month 3, the primary endpoint.
The company noted that a post-hoc analysis was performed by the masked central reading center in February 2022 based on an OCT (Optical Coherence Tomography) biomarker assessment. The analysis identified two subjects with abnormalities at baseline, which could impact responsiveness to any medical treatment.
Moreover, the company noted that excluding these two subjects resulted in an improvement in mean BCVA of 9.3 letters at Month 3, which was sustained until Month 6, the end of the trial, and four months after the last THR-149 injection. The Month 6 data also demonstrated THR-149’s attractive safety profile and its ability to stabilize the Central Subfield Thickness (CST). The learnings from the Part A data were incorporated into Part B through an amended trial design excluding patients that would not respond to any treatment.