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1. OBJECTIVES
The goal of this clinical trial report is to examine the safety and efficacy of GS441524 based oral capsules by CURE FIP™ for the treatment of cats with various types of naturally acquired feline infectious peritonitis (FIP). Oral treatment is a desirable treatment option for cats that experience difficulties with subcutaneous injections.
2. INTRODUCTION
GS-441524 nucleoside analogue was established as an effective antiviral treatment for feline infectious peritonitis several years ago by a team of researchers in the University of California, Davis. Since then tens of thousands of cats have been saved globally using the injection form of GS-441524. However, there are some inherent shortcomings associated with injections including severe skin irritations, aversion to injections and difficulty to administer injections towards the latter part of the treatment as cats acquires the strength to struggle. The creation of an oral form of feline infectious peritonitis treatment attempts to overcome these inherent shortcomings and provides veterinary professionals and cat owners a more convenient way to deliver GS-441524 to feline infectious peritonitis infected cats on a daily basis.
The goals of developing oral GS-441524 capsules are:
To develop an easy to administer oral treatment that cat owners can use without the assistance of a veterinary professional.
To achieve similar therapeutic performance as GS-441524 injections.
To reduce the likelihood of relapses traditionally associated with oral GS-441524 treatments from other brands.
43 FIP infected cats participated in our clinical study. All cats are clinically diagnosed FIP by veterinarians.
We aimed to reproduce the natural conditions under which oral capsules may be used by cat owners during a FIP treatment. Thus, the clinical trials were conducted at homes, and administered daily by cat owners instead of veterinary professionals.
All oral forms of GS441524 currently sold on the market are in compressed powder tablets. We selected oral capsules over tablets for a few reasons. Capsules are easy to administer as they are odourless and tasteless. Capsules cause less gastrointestinal irritations. Most importantly, should it be difficult to insert the capsules into the cat's mouth, cat owners can open the capsules and mix the content with cat food or snacks.
Cat owners who participated in our trial study administered the oral capsules using 3 possible methods:
Insert the capsules directly to the back of the mouth.
Mix capsules in with wet cat treats or wet cat food during feeding sessions.
Separate the gel caps and pour the content on top of the cat food.
3. METHODOLOGY
The trial began with 43 FIPV-infected cats ranging in age from 5 to 96 months. All the cats in the trial were diagnosed as having one of two forms of FIP: non-effusive (dry), effusive (wet), with 5 participants exhibiting ocular or neurological symptoms. These participants are divided into two phases of oral treatment. The duration of each phase is 30 days. This report will conclude the findings of all 43 cats after their completion of the first 30 days of oral treatment. There are 13 cats that showed no clinical signs of FIP after completing 30 days of our oral treatment. These Cats had their blood tests taken and were put on observation after blood tests results showed that the parameters are within normal ranges. We will first focus on the data of 13 cats, then on the 25 cats that still showed clinical symptoms of FIP after 30 days of treatment, and continued on to another 30 days of treatment. A report of the second 30 days phase of the trial will be updated once they have completed 60 days of oral treatment, and their blood test reports are completed. Several cats that participated in our study were part time outdoor cats. Of these cats, 2 of the 43 cats recovered sufficiently within the 30 days of treatment to warrant return to normal outdoor exposures. Their owners reported that they went missing and never returned. We received daily updates from their owner until the date of their disappearance. Their information is also presented in this report, but will be excluding blood test reports after the first.
Table 1 classifies the breeds of the participating cats. The treatment was given at various dosages according to the weight of the cats. All cats were required to complete a pre-treatment blood test. Cats that were unable to feed by themselves were required to complete 2 weeks of GS-441524 injections or until they were able to eat and defecate normally before entering into the clinical study. All cats instructed to complete a blood test after 30 days of treatment to measure changes in key blood test markers.
Bodyweight was chosen as the only determining factor for the oral treatment dosage. Type of FIP and symptoms were non-determining factors for the purpose of this clinical trial.
Code | Breed | Age | Type of FIP |
COT001 | Domestic Shorthair | 2 | Wet |
COT002 | Domestic Shorthair | 0.3 | Wet |
COT003 | Domestic Shorthair | 0.75 | Dry |
COT004 | Domestic Shorthair | 0.75 | Wet |
COT005 | Domestic Shorthair | 18 | Wet |
COT006 | Domestic Shorthair | 8 | Dry |
COT007 | Domestic Longhair | 1 | Dry |
COT008 | Tabby | 6 | Wet |
COT009 | Tabby | 1 | Dry |
COT010 | British Shorthair | 3 | Wet |
COT011 | Domestic Shorthair | 1 | Wet |
COT012 | Domestic Shorthair | 0.5 | Wet |
COT013 | Domestic Shorthair | 1 | Dry |
COT014 | Munchkin | 3 | Wet |
COT015 | Domestic Longhair | 1.5 | Neurological |
COT016 | Domestic Longhair | 9 | Dry |
COT017 | Domestic Shorthair | 7 | Wet |
COT018 | Domestic Shorthair | 1.5 | Wet |
COT019 | British Shorthair | 3 | Wet |
COT020 | Domestic Shorthair | 3 | Wet |
COT022 | Domestic Shorthair | 0.9 | Wet |
COT023 | Domestic Shorthair | 5 | Dry |
COT024 | Domestic Longhair | 2 | Wet |
COT025 | British Shorthair | 2 | Dry |
COT026 | British Shorthair | 0.6 | Wet |
COT027 | Domestic Shorthair | 2 | Wet |
COT028 | Domestic Shorthair | 0.9 | Dry |
COT029 | Domestic Shorthair | 10 | Wet |
COT030 | Domestic Shorthair | 0.6 | Dry |
COT031 | Siberian | 2 | Dry |
COT032 | Tabby | 7 | Neurological |
COT033 | Domestic Longhair | 4 | Wet |
COT034 | Domestic Shorthair | 6 | Dry |
COT035 | Persian | 3 | Neurological |
COT036 | Domestic Shorthair | 1 | Dry |
COT037 | Domestic Shorthair | 7 | Dry |
COT038 | Domestic Shorthair | 5 | Wet |
COT039 | Domestic Shorthair | 7 | Wet |
COT040 | Domestic Shorthair | 3 | Wet |
COT041 | Domestic Shorthair | 1 | Dry |
COT042 | Domestic Shorthair | 2.5 | Ocular |
COT043 | Domestic Shorthair | 3 | Wet |
COT044 | Domestic Shorthair | 2 | Dry |
TABLE 1 shows breed type cats participating in this clinical trial
4. RESULT & DISCUSSION
4.1 TREATMENT OUTCOME
After 30 days, 13 cats successfully exited the treatment. 25 cats continued the oral treatment for another 30 days. 2 cats went missing after being allowed to roam outdoors. 3 cat owners stopped updating the daily progress tracking sheet and stopped communicating with us despite repeated attempts to contact them. In this report, we will illustrate the data of the 43 cats after the first 30 days of treatment.
Table 2 shows the initial globulin and albumin/globulin readings in column 2 and 3, and after 30 days globulin and albumin/globulin readings of the 13 cats who successfully exited the oral clinical study after 30 days of oral treatment.
Cat Code | Globulin Reading (pre-treatment) | A/G Ratio (pre-treatment) | Globulin Reading After 30 Day | A/G Ratio After 30 Days |
COT002 | 5.2 | 0.60 | 4.7 | 0.70 |
COT005 | 4.3 | 0.60 | 4.5 | 0.60 |
COT006 | 6.8 | 0.40 | 4.5 | 0.60 |
COT013 | 3.3 | 1.24 | 3.5 | 0.90 |
COT020 | 7.9 | 0.29 | 4.5 | 0.73 |
COT022 | 7.2 | 0.40 | 5.9 | 0.5 |
COT024 | 5.1 | 0.50 | 4.4 | 0.70 |
COT025 | 7.8 | 0.30 | No Data | No Data |
COT026 | 4.7 | 0.50 | 4.1 | 0.80 |
COT027 | 5.3 | 0.50 | 4.3 | 0.70 |
COT030 | 7.4 | 0.26 | 4.7 | 0.55 |
COT031 | 5.1 | 0.50 | 4.4 | 0.70 |
COT041 | 3.9 | 0.60 | 3.7 | 1.0 |
TABLE 2 shows the reading of globulin and A/G ratio in clinical trial
*COT025's owner cited financial constraints as the reason for not completing a blood test after 30 days of oral treatment.
The normal range of globulin reading ranges between 2.8g/dL - 4.8g/dL meanwhile the normal reading of A/G ratio are above 0.6. Both effusive (wet) and non-effusive (dry) forms of FIP infected cats had an increase in the A/G ratio after the oral capsule treatment. A/G ratio alerts veterinarians to potential liver or kidney problems. An increase in the A/G ratio of the non-effusive (dry) FIP cat were more significant (75%) than those of the effusive (wet) FIP cat (18 %).
Graph 1. The globulin readings in 12 of the 13 cats improved significantly during FIP treatment. Cat’s natural immune system, responding to FIP infection, triggered antibodies production, causing the globulin readings to be high prior to our oral FIP therapy.
In Graph 2, the A/G ratio of 13 cats who exited the treatment after 30 days showed significant improvement. The increased A/G ratios indicate a reduction of white blood cells in the blood system, demonstrating that the oral capsules were effective in treating FIP in cats. Higher serum protein linked with high globulin and low albumin, and a low A/G ratio are common abnormalities during a FIP infection. Therefore, when these typical anomalies are combined with the standard signalment and clinical indications, FIP can be diagnosed with high certainty.
4.2 COMPLETE BLOOD COUNT (CBC)
Cat Code | White Blood Cell (Pre-treatment) | White Blood Cell After 30 Days | Lymphocytes (Pre-treatment) | Lymphocytes After 30 Days |
COT002 | 13.4 | 6.10 | 6.30 | 2.90 |
COT005 | 17.3 | 4.30 | 0.90 | 1.10 |
COT006 | 14.4 | 10.82 | 6.50 | 2.80 |
COT013 | 9.3 | 11.60 | 4.10 | 3.20 |
COT020 | 10.9 | 5.64 | 7.80 | 3.58 |
COT022 | 13.32 | 10.55 | 1.33 | 0.98 |
COT024 | 17.8 | 5.10 | 1.90 | 0.90 |
COT025 | 35.02 | No Data | 5.25 | No Data |
COT026 | 19.7 | 11.00 | 6.43 | 3.25 |
COT027 | 19.2 | 24.47 | 6.56 | 3.86 |
COT030 | 5.4 | 12.90 | 1.80 | 1.30 |
COT031 | 13.8 | 10.80 | 6.20 | 2.70 |
COT041 | 34.28 | 13.47 | 8.25 | 1.83 |
TABLE 3 shows the reading of blood count of the 13 cats that exited treatment after 30 days.
Table 3 depicts the improvements of CBCs and lymphocytes of 13 cats during the course of 30 days of FIP treatment. A little decline and increase in white blood cells indicate that the blood system's regulation is returning to normal.
4.3 WEIGHT CHANGES OF THE 13 CATS THAT COMPLETED TREATMENT IN 30 DAYS.
Cat Code | Weight Before Treatment (Kg) | Weight After 30 Days Treatment (Kg) | Increase of Number (Kg) |
COT002 | 1.80 | 2.14 | 0.34 |
COT005 | 1.90 | 2.60 | 0.70 |
COT006 | 2.05 | 2.47 | 0.42 |
COT013 | 2.90 | 3.00 | 0.10 |
COT020 | 3.00 | 3.00 | 0 |
COT022 | 2.7 | 3.2 | 0.5 |
COT024 | 4.10 | 4.40 | 0.30 |
COT025 | 3.3 | 3.4 | 0.10 |
COT026 | 1.96 | 2.6 | 0.64 |
COT027 | 1.05 | 1.80 | 0.75 |
COT030 | 1.80 | 2.31 | 0.51 |
COT031 | 3.50 | 3.95 | 0.45 |
COT041 | 3.10 | 3.40 | 0.30 |
TABLE 4 shows the weight of the 13 cats that exited treatment after 30 days.
12 out of the 13 cats showed weight gains. This indicates that these cats regained their appetite and muscle mass within the first 30 days of oral treatment (Table 4). All 13 cats demonstrated normal appetite after 30 days. Despite globulin increased by 0.2 at the end of 30 days, COT005 gained 0.75 kg with visible improvement in appetite. The weight measurements were taken at the home of each cat, using commercially available household scales.
4.4 BLOOD RESULTS OF 25 CATS THAT DIDN'T EXIT THE PROGRAM AFTER 30 DAYS
Cat Code | Globulin Readings (Pre-Treatment) | Globulin Readings (After 30 Days Treatment) | A/G Ratio (Pre-Treatment) | A/G Ratio (After 30 Days Treatment) |
COT003 | 4.6 | 4.2 | 0.6 | 0.7 |
COT004 | 5.7 | 5.4 | 0.5 | 0.5 |
COT007 | 5.4 | 5.2 | 0.4 | 0.56 |
COT008 | 6.1 | 6.4 | 0.5 | 0.5 |
COT009 | 7.1 | 5.9 | 0.5 | 0.6 |
COT010 | 7.1 | 6.1 | 0.4 | 0.5 |
COT011 | 5.7 | 5.5 | 0.63 | 0.6 |
COT012 | 6.8 | 5.2 | 0.4 | 0.5 |
COT014 | 6.5 | 6.5 | 0.3 | 0.4 |
COT015 | 7 | 6.1 | 0.4 | 0.4 |
COT016 | 5.4 | 4.9 | 0.5 | 0.6 |
COT017 | 8.9 | 6.1 | 0.3 | 0.5 |
COT018 | 9 | 5.5 | 0.3 | 0.6 |
COT019 | 3.8 | 5.5 | 0.6 | 0.6 |
COT023 | 5.1 | 5.7 | 0.5 | 0.5 |
COT029 | 7.36 | 6.5 | 0.26 | 0.4 |
COT032 | 6.3 | 7.5 | 0.4 | 0.4 |
COT033 | 7.4 | 8.3 | 0.26 | 0.4 |
COT034 | 10.2 | 6.9 | 0.2 | 0.23 |
COT036 | 7.5 | 6.1 | 0.4 | 0.46 |
COT037 | 7.3 | 5.4 | 0.4 | 0.5 |
COT038 | 7.5 | 5.4 | 0.4 | 0.5 |
COT042 | 9 | 3.7 | 0.3 | 1.1 |
COT043 | 6 | 6.7 | 0.5 | 0.4 |
COT044 | 5.8 | 5.2 | 0.6 | 0.6 |
TABLE 5 Shows the list of cats that participate for 30 days treatment (Globulin and A/G Ratio)
4.5 WEIGHT OF 25 CATS THAT DIDN'T EXIT THE PROGRAM AFTER 30 DAYS
Cat Code | Weight Of Cat (KG) (Pre-treatment) | Weight Of Cat (KG) (After 30 Days Treatment) |
COT003 | 2.7 | 3.13 |
COT004 | 3.45 | 3.63 |
COT007 | 2.5 | 2.7 |
COT008 | 5.7 | 5.95 |
COT009 | 2.55 | 2.7 |
COT010 | 4 | 4.26 |
COT011 | 3.2 | 3.3 |
COT012 | 1.87 | 2.27 |
COT013 | 2.9 | 3.0 |
COT014 | 2.84 | 3.33 |
COT015 | 2.34 | 3.09 |
COT016 | 2.45 | 3.1 |
COT017 | 4.02 | 4.54 |
COT018 | 4.3 | 4.5 |
COT019 | 4.56 | 3.88 |
COT023 | 2.54 | 2.74 |
COT029 | 2.4 | 3.51 |
COT032 | 4.5 | 4.65 |
COT033 | 2.9 | 3.4 |
COT034 | 2.64 | 2.71 |
COT036 | 1.77 | 2.44 |
COT037 | 2.55 | 2.8 |
COT038 | 2.50 | 2.8 |
COT042 | 4.1 | 4.1 |
COT043 | 3.3 | 3.56 |
COT044 | 3.2 | 3.4 |
TABLE 6 Shows the list of cats that participate for 30 days treatment (Weight)
Due to factors outside of our control, 5 cats were not able to complete the first 30 days of treatment. 2 cats (COT001 and COT0039) were outdoor cats. When the cats became healthy enough to move about, the owner release the cats outdoors. They have since gone missing. 3 cat owners (COT 028, COT 035, and COT 040) has stopped responding to our request for updates since the commencement of the trial. We could not obtain daily updates nor blood tests after repeated requests. We understood these risks when designing our real world clinical trial. Our aim was to replicate, as faithful as possible, real world situations and the uses of our capsules.
Based on Table 5, COT003 globulin value dropped and AG ratio is raised to 0.7 which is a good value for the cat to stop treatment. However, the reason the cat continued on with the next 30 days was because COT003 had cloudy eyes when it first started and cloudiness remained even after 30 days of oral treatment.
5. CONCLUSION
The initial findings indicate that our GS-441524 based oral capsules are an effective treatment against effusive (wet) and non-effusive (dry) feline infectious peritonitis (FIP). The results achieved by the 13 cats who exited the treatment study were stellar. The remaining 25 cats showed steady improvements toward full recovery. We will publish a follow up report on the 25 cats upon their completion of an additional 30 days treatment, and after their cat owners complete another set of blood tests.
6. REFERENCES
[1] Geoffrey Migiro, “How Many Cats Are There in the World?Philippines” WorldAtlas.com, 7 November 2018, https://www.worldatlas.com/articles/how-many-cats-are-there-in-the-world.html. Accessed 6 Nov. 2020.
[2] Niels C. Pedersen, Michel Perron, Michael Bannasch, Elizabeth Montgomery, Eisuke Murakami, Molly Liepnieks, and Hongwei Liu, Efficacy and safety of the nucleoside analog GS-441524 for treatment of cats with naturally occurring feline infectious peritonitis, J. Feline Med. Surg. 2019; 271–281.
[3] Peter J. Dickinson, Michael Bannasch, Sara M. Thomasy, Vishal D. Murthy, Karen M. Vernau, Molly Liepnieks, Elizabeth Montgomery, Kelly E. Knickelbein, Brian Murphy, Niels C. Pedersen, Antiviral treatment using the adenosine nucleoside analogue GS -441524 in cats with clinically diagnosed neurological feline infectious peritonitis, J. Vet. Intern. Med. 2020; 1-7.
[4] "Veterinary advancements in managing Feline Infectious Peritonitis (FIP) in cats". Australian Veterinary Association Ltd. 19 February 2021.
[5] Addie D., Belák S., Boucraut-Baralon C., Egberink H., Frymus T., Gruffydd-Jones T., Hartmann K., Hosie M.J., Lloret A., Lutz H., et al.Feline infectious peritonitis. ABCD guidelines on prevention and management Journal of Feline Medicine and Surgery, 11 (2009), pp. 594-604