Elsevier

Ophthalmology

Volume 114, Issue 10, October 2007, Pages 1822-1830.e2
Ophthalmology

Original article
A Phase III Study of Subconjunctival Human Anti–Transforming Growth Factor β2 Monoclonal Antibody (CAT-152) to Prevent Scarring after First-Time Trabeculectomy

https://doi.org/10.1016/j.ophtha.2007.03.050Get rights and content

Objective

To evaluate CAT-152 (lerdelimumab), a monoclonal antibody to transforming growth factor-β2 (TGF-β2), 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 μg in 100 μl 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 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.

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.

Section snippets

Study Design

This multicenter, double-masked, randomized, placebo-controlled trial examined the use of a human monoclonal antibody to TGF-β2 (CAT-152) as an adjunct to first-time trabeculectomy. Each patient was treated in 1 eye. Patients were enrolled at 36 sites in 6 countries. The study conformed with the principles of the Declaration of Helsinki, with the good clinical practice protocols of the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for

Study Population

A total of 354 patients consented to enter the study; 343 were randomized to receive either placebo or CAT-152; 96% (n = 330) of the randomized patients completed the trial (Fig 1). The ITT analyses were conducted using the data from 2 sets of patients: (1) those diagnosed with POAG or CACG (POAG/CACG group; n = 274); and (2) patients diagnosed with POAG, CACG, PEXG, or PG (+PEXG/PG group; n = 338). Analysis of the safety of CAT-152 was carried out on all patients treated (safety group; n =

Discussion

In this study, CAT-152, an antibody to TGF-β2, was administered as an adjunctive treatment to delay or prevent scarring at the bleb site to patients receiving first-time trabeculectomy for intractable glaucoma. On the primary end point of treatment success (IOP lowering to the target range in the absence of medication or repeat surgery) and the secondary end points of success of surgery, time to surgical failure, IOP, and bleb site anatomic features, no statistically significant difference

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    Manuscript no. 2006-1173.

    Supported by Cambridge Antibody Technology, Cambridge, United Kingdom, and in part by the Biomedical Research Centre, National Institute for Health, Department of Health, London, United Kingdom.

    See Appendix (available at http://aaojournal.org) for Study Group membership.

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