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

Abstract

OBJECTIVE:

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).

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 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.

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.

• Authors: CAT-152 0102 Trabeculectomy Study Group, Peng Khaw, Franz Grehn, Gábor Holló, Barry Overton, Rosamund Wilson, Roger Vogel, Zaid Smith
• Journal: Ophthalmology (Ophthalmology) Vol. 114 Issue 10 Pg. 1822-30 (Oct 2007) ISSN: 1549-4713 [Electronic] United States
• PMID: 17908591 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Transforming Growth Factor beta2
• Lerdelimumab

Topics

• Adult
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal (administration & dosage)
• Antibodies, Monoclonal, Humanized
• Chronic Disease
• Combined Modality Therapy
• Conjunctiva (drug effects, pathology)
• Double-Blind Method
• Exfoliation Syndrome (surgery)
• Female
• Fibrosis (prevention & control)
• Glaucoma, Angle-Closure (surgery)
• Glaucoma, Open-Angle (surgery)
• Humans
• Intraocular Pressure
• Male
• Middle Aged
• Prospective Studies
• Tonometry, Ocular
• Trabeculectomy
• Transforming Growth Factor beta2 (immunology)
• Treatment Outcome