A blinded, randomized, placebo-controlled trial of the safety of lokivetmab (ZTS-00103289), a caninized anti-canine IL-31 monoclonal antibody in client-owned dogs with atopic dermatitis.

BACKGROUND: Lokivetmab (ZTS-00103289) is a caninized anti-canine IL-31 monoclonal antibody that has demonstrated efficacy in reducing pruritus associated with atopic dermatitis (AD) in dogs in field trials. HYPOTHESIS/OBJECTIVES: This study evaluated the safety of lokivetmab in a randomized, double blind, placebo-controlled trial in client owned dogs with AD with minimal restrictions on concomitant medications and co-morbidities. ANIMALS: Clinicians at 14 veterinary clinics enrolled client owned dogs (n = 245) with chronic AD. METHODS: Dogs were randomized at a 2:1 ratio to receive either lokivetmab (1.0-3.3 mg/kg) or placebo administered subcutaneously on days 0 and 28. Clinicians examined dogs, and collected blood and urine for assessment of clinical pathology and immunogenicity (days 0, 28 and 42). RESULTS: There were no immediate hypersensitivity reactions (e.g. wheals, vomiting). Discomfort at administration occurred in 5.1% of dogs and was similar in frequency and severity between lokivetmab- and placebo-treated groups. Pruritus was reported as an adverse event during the study less frequently in the lokivetmab-treated group (4.9% and 19.3%, respectively); otherwise, adverse events occurred at a similar frequency between treatment groups. There were no clinically important differences between groups in clinical pathology results. Treatment-induced immunogenicity was found in 2.5% of lokivetmab treated dogs. A wide variety of concomitant medications were used with no clinically apparent adverse interactions. CONCLUSIONS AND CLINICAL IMPORTANCE: Among a diverse population of 162 client owned dogs with a clinical diagnosis of AD, treatment with two monthly doses of lokivetmab was safe, based on observed adverse events and clinical pathology results over a 42 day period.

A blinded, randomized, placebo-controlled, dose determination trial of lokivetmab (ZTS-00103289), a caninized, anti-canine IL-31 monoclonal antibody in client owned dogs with atopic dermatitis.

BACKGROUND: Pruritus is the hallmark clinical sign of atopic dermatitis (AD) in dogs. Lokivetmab, a caninized anti-canine IL-31 monoclonal antibody, reduced pruritus and associated inflammatory skin lesions in a proof-of-concept study in dogs with AD. HYPOTHESIS/OBJECTIVES: The objective was to describe lokivetmab dose response in a randomized, double blind, placebo-controlled trial. ANIMALS: Clinicians at 15 referral clinics enrolled 211 client owned dogs with a history of chronic AD. METHODS: Dogs were randomized to treatment with lokivetmab (0.125, 0.5 or 2.0 mg/kg) or placebo administered subcutaneously once on Day 0. Dog owners assessed visual analog scale (VAS) scores of pruritus on days 0, 1, 2, 3, 7, 14, 21, 28, 35, 42, 49 and 56. Clinicians assessed Canine AD Extent and Severity Index (CADESI-03) scores on days 0, 7, 14, 28, 42 and 56. RESULTS: Treatment with lokivetmab (2 mg/kg) resulted in a greater percentage reduction from baseline in owner assessed pruritus (days 1-49) and clinician assessed CADESI-03 scores (days 7-56) compared to placebo (P < 0.05); differences were achieved in lower dose groups but at later time points and for shorter duration for both owner assessed pruritus (0.5 mg/kg, days 2-35; 0.125 mg/kg, days 7-21) and clinician assessed CADESI-03 scores (0.5 mg/kg and 0.125 mg/kg, Day 14). CONCLUSIONS AND CLINICAL IMPORTANCE: Lokivetmab (0.5, 2.0 mg/kg) reduced pruritus compared to placebo for at least 1 month. Level and duration of response increased with increasing dose. Further studies are needed to better understand variability in individual responses across a broader population of dogs with AD.