A phase III study of subconjunctival human anti-transforming growth factor beta(2) monoclonal antibody (CAT-152) to prevent scarring after first-time trabeculectomy.

To evaluate CAT-152 (lerdelimumab), a monoclonal antibody to transforming growth factor-beta2 (TGF-beta2), in preventing the progression of fibrosis in patients undergoing first-time trabeculectomy for primary open-angle (POAG) or chronic angle-closure glaucoma (CACG). Randomized, double-masked, multicenter, placebo-controlled trial. 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. Patients received unilateral trabeculectomy with either 4 subconjunctival injections of CAT-152 (100 microg in 100 microl 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. 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. 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 PG (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. 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.