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

This study has been terminated.
(Futility)
Sponsor:
Collaborators:
Immune Tolerance Network (ITN)
Tunitas Therapeutics
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT01292070
First received: February 7, 2011
Last updated: January 6, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Cat Allergy
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
Phase 0

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • 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 [ Time Frame: up to 3 hours after the last injection of GFD ] [ Designated as safety issue: No ]
    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.


Enrollment: 4
Study Start Date: March 2011
Study Completion Date: April 2011
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Control-Experimental arm
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

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.

Biological: Positive Control - standardized cat hair allergenic extract (CAT)
4 sequential 10-fold injections starting from 0.01 BAU/mL to 10 BAU/mL
Biological: Positive Control - Histamine Prick
1.0 mg/mL
Other Name: Histatrol GLY
Biological: Negative Control - Intradermal Diluent
Saline, Albumin with Phenol (HSA) sterile diluent

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01292070

Locations
Australia, Victoria
Alfred Hospital and Monash University
Melbourne, Victoria, Australia, 3004
Sponsors and Collaborators
Immune Tolerance Network (ITN)
Tunitas Therapeutics
Investigators
Study Chair: Andy Saxon, MD, PhD University of California, Los Angeles (UCLA)
  More Information

Additional Information:
No publications provided

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT01292070     History of Changes
Other Study ID Numbers: DAIT ITN048AD
Study First Received: February 7, 2011
Results First Received: January 6, 2014
Last Updated: January 6, 2014
Health Authority: United States: Federal Government
Australia: Department of Health and Ageing Therapeutic Goods Administration
Australia: Human Research Ethics Committee

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Fel d 1 protein, Felis domesticus
Injections, Intradermal

Additional relevant MeSH terms:
Hypersensitivity
Immune System Diseases
Histamine
Histamine Agents
Histamine Agonists
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 22, 2014