CANBERRA: A Phase II Randomized Clinical Trial to Test the Therapeutic Potential of Oral Vicasinabin in Diabetic
Beatriz G Armendariz1, Ulrich F O Luhman1, Brian Berger2
1Roche Pharmaceutical Research and Early Development, Translational Medicine Ophthalmology, Roche Innovation Center, Basel, Switzerland.
Objective:
Nonproliferative diabetic retinopathy (NPDR) is a progressive disease that can lead to blindness. Current therapies for NPDR are invasive and not extensively used or accessible until the disease progresses, pointing to the need for an early noninvasive treatment. The objective of CANBERRA was to assess the safety, tolerability, and efficacy of oral administration of vicasinabin (RG7774) on the severity of diabetic retinopathy (DR) in participants with moderately severe to severe NPDR and good vision.
Design:
CANBERRA was a global, multicentric randomized, double-masked, parallel-group, placebo-controlled, phase II study. The study duration was 36 months.
Participants:
A total of 139 treatment-naïve patients with type 1 or type 2 diabetes mellitus and Diabetic Retinopathy Severity Scale (DRSS) levels of 47 or 53 in ≥1 eye were enrolled.
Intervention:
Eligible patients were randomized 1:1:1 to 36 weeks of daily oral placebo, vicasinabin 30 mg, or vicasinabin 200 mg. Participants were followed for an additional 12 weeks.
Main Outcome Measures:
The primary safety objective was to evaluate the safety and tolerability of vicasinabin by the frequency and severity of adverse events (AEs). The primary efficacy objective was to assess the effect of vicasinabin on the severity of DR, assessing the proportion of participants with ≥2-step improvement in DRSS from baseline at week 36 in the study eye.
Results:
Results are presented in the following order: placebo, vicasinabin 30 mg, vicasinabin 200 mg; 47, 48, and 44 participants were enrolled. Baseline characteristics were balanced. Adherence to treatment was approximately 90%, and pharmacokinetic analysis showed dose-dependent plasma exposure to vicasinabin. The primary efficacy endpoint was not met: the percentage of participants who improved their DRSS by ≥2 steps at week 36 from baseline were 7.9, 9.5, and 5.7, without statistically significant differences. The systemic and ocular safety profiles of vicasinabin were favorable, and AEs distributed evenly across arms. Vicasinabin did not induce changes in glycemic control or any kidney function or cardiovascular parameters. Three patients in the placebo arm discontinued the study due to serious AEs not related to the drug.
Conclusions:
At the doses tested, vicasinabin did not improve DRSS in participants with NPDR. The role of the cannabinoid system in DR remains elusive.
Trial Registration:
ClinicalTrials.gov identifier: NCT04265261. EUDRACT number: 2019-002067-10.
Financial Disclosures:
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Insights
Oral vicasinabin did not improve diabetic retinopathy severity in a phase II trial. The drug showed a favorable safety profile but did not meet its primary efficacy endpoint for nonproliferative diabetic retinopathy.
Area of Science:
- Ophthalmology
- Diabetology
- Pharmacology
Background:
- Nonproliferative diabetic retinopathy (NPDR) is a leading cause of blindness, necessitating early, noninvasive treatments.
- Current NPDR therapies are often invasive and inaccessible until disease progression, highlighting a critical unmet need for early intervention.
Purpose of the Study:
- To evaluate the safety, tolerability, and efficacy of orally administered vicasinabin (RG7774) in patients with moderately severe to severe NPDR.
- To assess the impact of vicasinabin on diabetic retinopathy (DR) severity using the Diabetic Retinopathy Severity Scale (DRSS).
Main Methods:
- CANBERRA was a 36-month, global, randomized, double-masked, placebo-controlled phase II study.
- 139 treatment-naïve patients with type 1 or 2 diabetes and NPDR were randomized to placebo, vicasinabin 30 mg, or vicasinabin 200 mg daily for 36 weeks.
- The primary efficacy endpoint was the proportion of participants with a ≥2-step improvement in DRSS from baseline at week 36.
Main Results:
- Vicasinabin demonstrated a favorable safety and tolerability profile, with adverse events evenly distributed across treatment arms.
- The primary efficacy endpoint was not met; improvement rates (≥2-step DRSS change) were 7.9% (placebo), 9.5% (30 mg), and 5.7% (200 mg), with no statistically significant differences.
- Vicasinabin did not affect glycemic control, kidney function, or cardiovascular parameters. Three patients on placebo discontinued due to unrelated serious adverse events.
Conclusions:
- Oral vicasinabin, at the tested doses, did not demonstrate efficacy in improving DRSS scores in patients with NPDR.
- The role of the cannabinoid system in the pathogenesis and treatment of diabetic retinopathy remains unclear.
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