Safety Evaluation of an Experimental Treatment, Intradermal Human Fcγ1-Fel d1 Fusion Protein (GFD), for Cat Allergy

Study Overview
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Brief Summary
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The purpose of this trial is to show that Intradermal Human Fcγ1-Fel d1 fusion protein (GFD) is able to block the skin reaction to cat allergen in cat allergic subjects compared to the skin reaction to cat allergen alone. This research project is also testing the safety and tolerability of this new, experimental treatment, compared to the current treatment of cat allergen alone.

Detailed Description
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Researchers are conducting a research study of a new protein developed to treat sensitivity to cat allergens. Cat allergy in humans is an allergic reaction to one or more of the five known allergens produced by cats. The most common of these is the protein Fel d 1. This study will test Intradermal Human Fcγ1-Fel d1 fusion protein (GFD), a new protein that, based on animal data, has been developed to block the allergic effects of cat. If this drug works the way they think it does, it may become a treatment for cat allergy that is faster than the currently available treatments and with fewer side effects. This protein contains the molecule from the cat, that causes the allergic reaction, attached to a section of a particular antibody (protein involved in immunity) called Fcγ1 that acts like a break. The fusion of the two proteins is predicted to interrupt the flow of cellular reactions which lead to the allergic response. This will be the first time GFD is administered to humans. The study will be conducted in two parts. The subjects in part A will be administered intradermal standardized cat hair allergenic extract (CAT) and GFD sequentially in 10-fold increasing doses every 20 minutes. If Part A demonstrates the safety of GFD,subject in part B will begin by following the same treatment as part A followed by a rechallenge of the sites with CAT at 4 hours after the first dose of GFD. Each subject will be evaluated 3 times (screening, dosing, and telephone follow-up 2 days post dosing) and will return on Day 28 for blood draw.

Official Title
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A Dose-Escalating Phase 0 Study to Evaluate the Safety and Local Cutaneous Reactivity of Intradermal Human Fcγ1-Fel d1 Fusion Protein (GFD) in Cat-allergic Healthy Volunteers

Conditions
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Cat Allergy

Intervention / Treatment
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* Biological: Intradermal Human Fcγ1-Fel d1 fusion protein
* Biological: Positive Control - standardized cat hair allergenic extract (CAT)
* Biological: Positive Control - Histamine Prick
* Biological: Negative Control - Intradermal Diluent


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: History of allergic reactivity to cats as expressed by allergic rhinitis Radioallergosorbent test (RAST test) for cat-specific IgE with RAST rating of 2 (0.70-3.49 KU/L IgE) documented within the past year or at screening Standardized cat hair allergenic extract (CAT), 10,000 BAL/mL (ALK-Abello) elicits a wheal 5 mm or greater than the diluent control (Saline Albumin with Phenol [HSA], ALK-Abello) with surrounding erythema on testing using a standardized epicutaneous delivery device (Stallergenes Prick Lancet, 1 mm tip) Histamine (Histatrol 1mg/mL, ALK-Abello) reactivity of 5 mm or greater reactivity than the diluent control with surrounding erythema on epicutaneous testing using a standardized epicutaneous delivery device Able and willing to discontinue any anti-histamine use for 5 days prior to entry into protocol and throughout the protocol participation Baseline spirometry (FEV1, FVC FEF25-75) with FEV1 >=80% predicted and other values within the normal range Ability to give written informed consent Exclusion Criteria: Diluent control (Saline Albumin with Phenol [HSA], ALK-Abello) elicits wheal >= 3 mm on epicutaneous testing using a standardized epicutaneous delivery device Pregnant females as determined by a positive serum or urine hCG test Lactating females Ever having received allergen immunotherapy (e.g., -subcutaneous allergen [SCIT] or -sublingual [SLIT]) Systemic steroids in the past 3 months Severe systemic reactivity on exposure to cats (e.g., laryngeal or angioedema, fainting, pallor, bradycardia, hypotension, bronchospasm, asthma, or generalized urticaria) A clinical history of asthma Underlying heart, liver, kidney lung, or other medical condition (acute infections, immune diseases, current substance abuse) such that the person would be at a clearly increased risk for a poor outcome should a generalized allergic reaction occur Use of systemic beta-blocking or ACE-inhibiting agents within the past 3 weeks Use of tri-cyclic antidepressants within the past 3 weeks Subjects receiving therapy with any agents known or likely to interact with adrenaline (e.g., beta blockers, ACE-Inhibitors, tri-cyclic antidepressants, or other) Current use or use of omalizumab (Xolair) within past 6 months Subjects with any extensive skin disorder (atopic dermatitis) that would make skin testing or proper interpretation impractical Mental impairment, limiting the ability to comply with study requirements Participation in a clinical trial and receipt of an investigational product within 30 days, 5 half-lives or twice the duration of the biochemical effect of the investigational product (whichever is longer) prior to dosing in the current study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Control-Experimental arm<br>Each subject will serve as their own control with the left arm receiving the control protein (Histamine prick, intradermal diluent and intradermal CAT) and right arm receiving the experimental protein (GFD). | Biological: Intradermal Human Fcγ1-Fel d1 fusion protein<br>* Part A: 7 sequential 10-fold dose increments from 0.001 BAU/mL to 1,000 BAU/mL; An 8th dose of 10,000 BAU/mL might be given only if the 10 BAU/mL of CAT is the dose that elicits a bump or hive of >= to 10mm. Part B: 5 sequential 10-fold dose increments from 0.1 BAU/mL to 1,000 BAU/mL; An 6th dose of 10,000 BAU/mL might be given only if the 10 BAU/mL of CAT is the dose that elicits a bump or hive of >= to 10mm.<br>Biological: Positive Control - standardized cat hair allergenic extract (CAT)<br>* 4 sequential 10-fold injections starting from 0.01 BAU/mL to 10 BAU/mL<br>Biological: Positive Control - Histamine Prick<br>* 1.0 mg/mL<br>* Other names: Histatrol GLY;Biological: Negative Control - Intradermal Diluent<br>* Saline, Albumin with Phenol (HSA) sterile diluent<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in the Doses of GFD and CAT Required to Elicit a Cutaneous Reaction Demonstrated by a Wheal Greater Than or Equal to 10 mm With Surrounding Erythema | Difference in the doses of human Fcgamma1-Fel d1 (cat allergen) fusion protein (GFD) and standardized cat hair allergenic extract (CAT) required to elicit a wheal ≥ 10 mm with surrounding erythema. | up to 3 hours after the last injection of GFD | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fel d 1 protein, Felis domesticus, Injections, Intradermal