01663-A: Placebo-controlled trial of T-cell receptor (TCR) peptide treatment in dogs with non-responsive atopic dermatitis
Grant Status: Closed
Grant Amount: $12,960
Dr. Daniel A. Gingerich, D.V.M., Imulan Bio Therapeutics, LLC
May 1, 2011 - October 31, 2012
Sponsor(s): Westie Foundation of America, Inc.
Breed(s): -All Dogs
Disease(s): Atopic Dermatitis
Research Program Area: Dermatology and Allergic Disease
Project Summary Purpose. The objective of this placebo-controlled clinical trial was to determine the efficacy and safety of T-Cell receptor (TCR) peptide treatment of dogs with atopic dermatitis. The study has thus far been directly or indirectly supported by 3 separate Canine Health Foundation (CHF) ACORN grants (#857, #01240-A, and the present grant #01663-A).
Background. Atopic dermatitis is a frustrating, chronically relapsing allergic skin disease in dogs. Treatment options are limited; many dogs require prolonged administration of steroids or other immunosuppressive drugs. The only specific cure is skin testing and desensitization treatments over prolonged periods of time, managed by skilled veterinarians. Palliative treatments and newer immunosuppressive drugs such as cyclosporine (Atopica) are effective under carefully managed conditions.
It is now known that an underlying cause of atopic dermatitis in dogs is impaired immune responsiveness, specifically T-cell imbalance. In laboratory mice, TCR peptide treatment consistently rebalances T-cells and restores normal immunity. In dogs with atopic dermatitis, previous CHF-sponsored studies showed that TCR peptide treatment resulted in long lasting (60-90 days) improvement in itchiness and other signs of the disease, consistent with restoration of normal immune responsiveness. Furthermore, dogs with atopic dermatitis were found to have 16 fold higher anti-TCR antibody activity compared to normal dogs, suggesting new diagnostic tests.
Based on results of pilot trials, this larger randomized controlled trial was initiated in dogs with atopic dermatitis treated with TCR peptides or placebo.
Methods. This was a randomized controlled trial (RCT) in atopic dogs to compare the clinical effects of immunization with the classical TCR V 8.1 peptide and the corresponding canine ortholog (Dog TCR) with placebo. Peptides or placebo were injected subcutaneously at baseline and boosted at Week 2. Clinical evaluations were conducted at Weeks 0, 2, and 6. The primary outcome measure for effectiveness was improvement in the Canine Atopic Dermatitis Extent and Severity Index" (CADESI) score by veterinary dermatologists. Secondary outcome measures included evaluation of pruritus (itchiness) assessed by the dog owners. Sera were also collected before and after treatment for determination of IgG1, IgG2, and anti-TCR antibody reactivity. Safety was assessed by monitoring adverse events and by hematology and clinical chemistry determinations before and after treatment.
Results. Twenty eight atopic dogs were enrolled, of which 23 were qualified for efficacy evaluation, consisting of 8 dogs randomized to Group A (placebo), 6 to Group B (Dog TCR) and 9 to Group C (TCR V 8.1). Six of the placebo dogs were crossed over and immunized with known TCR peptides, resulting in 9 evaluable cases of Dog TCR and 12 of TCR V 8.1.
CADESI (severity) scores were comparable among treatment groups at baseline. Over the 6 week study period CADESI scores improved (went down) in 2/8 dogs in the placebo group, 3/6 dogs in the Dog TCR group and 7/9 dogs in the TCR V 8.1 group. Itchiness scores decreased significantly (p<0.05) in Dog TCR and TCR V 8.1 treatment groups, but not in the placebo group. Similar response rates were obtained when data from crossover dogs are included in the analysis. Regarding immunological assays, no consistent patterns in IgG1, IgG2 or anti-TCR antibody titers were apparent.
Safety. Adverse events were rarely encountered in any of the treatment groups, and were considered minor. No noteworthy abnormalities or significant changes over time in hematology or clinical chemistry data were detected in any of the dogs in any of the treatment groups.
Conclusions. Overall, the results of this study are strongly supportive of the efficacy of TCR V 8.1 peptide treatment for canine atopic dermatitis, somewhat supportive of Dog TCR peptide, and strongly supportive of the safety of either peptide.