A phase III study of subconjunctival human anti-transforming growth factor β2 monoclonal antibody (CAT-152) to prevent scarring after first-time trabeculectomy

Objective: To evaluate CAT-152 (lerdelimumab), a monoclonal antibody to transforming growth factor-ss(2) (TGF-beta(2)), in preventing the progression of fibrosis in patients undergoing first-time trabeculectomy for primary open-angle (POAG) or chronic angle-closure glaucoma (CACG). Design: Randomized, double-masked, multicenter, placebo-controlled trial. Participants: Individuals with a diagnosis of POAG, CACG, pseudoexfoliative glaucoma (PEXG), or pigmentary glaucoma (PG), with a recorded intraocular pressure (IOP) of more than 21 mmHg, visual field or optic disc changes characteristic of glaucoma, and taking the maximum tolerated dose of medication. Intervention: Patients received unilateral trabeculectomy with either 4 subconjunctival injections of CAT-152 (100 mu g in 100 mu l phosphate buffer) or 4 placebo injections, administered immediately before and on completion of trabeculectomy, and on the first day and at 1 week after surgery. Patients were followed up for 12 months after surgery. Main Outcome Measures: The primary outcome measure was treatment success in the study eye (unmedicated IOP of 6-16 mmHg inclusive), at the 6- and 12-month follow-up. Secondary outcome measures were the incidence of postoperative intervention with 5-fluorouracil (5-FU); incidence of surgical failure; time to surgical failure; and incidence of vascularity, microcysts, and encapsulation or demarcation of the bleb site. Results: Of the 388 patients evaluated in the trial, 81 % (n = 274) had either POAG or CACG, combined into a single set (POAG/CACG) analyzed by intent-to-treat (ITT) criteria. Separate ITT analyses were carried out for all participants (+ PEXG/PG group), with similar results. The treatment success rate was 60% in the CAT-152 group and 68% in the placebo group (P = 0.23). No statistically significant differences emerged in the secondary end points. Patients requiring 5-FU for postsurgical management were more likely to be treatment failures (P = 0.0003). Patients with a primary diagnosis of PIS (n = 49) had a higher success rate than those with other diagnoses (P = 0.0077). Administration of CAT-152 was not associated with an increased incidence of adverse events. The immunogenicity of CAT-152 was very low. Conclusions: At the dose level and regimen studied, there was no difference between CAT-152 and placebo in preventing the failure of primary trabeculectomy. The safety profile of CAT-152 was similar to that of placebo.