A Single Dose Study of the Efficacy, Safety, Tolerability, and Pharmacokinetics of REGN1908-1909 in Allergic Rhinitis Patients Challenged Intranasally with Allergen Extract

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 20

Inclusion Criteria

1. Generally healthy men and women between the ages of 18 and 55, inclusive;
2. Body mass index (BMI) between 18.0 kg/m2 and 32.0 kg/m2, inclusive;
3. History of allergic rhinitis which is exacerbated by exposure to cats;
4. Cat sensitization confirmed at screening by both: i) positive skin prick test with cat hair extract (mean wheal diameter at least 3mm greater than negative control) ii) positive allergen-specific IgE tests for cat dander and Fel d 1 *0.35 kAU/I for both allergens);
5. Positive NAC (which is defined as a peak TNSS score >7 [on a 12-point scale], and with
a prechallenge TNSS *2) upon nasal allergen challenge with cat hair extract at screening
6. Normal lung function as judged by the investigator. Asthma subjects must have forced expiratory volume in 1 second (FEV1) * 80% of expected value at screening.
7. Willing and able to comply with clinic visits and study-related procedures
8. Provide signed informed consent
9. Able to understand and complete study-related questionnaires

Exclusion Criteria

1. Persistent chronic or active recurring infection requiring treatment with antibiotics,
antivirals, or antifungals or untreated respiratory infections within 4 weeks prior to the
screening visit.
2. Serum creatinine, alkaline phosphatase, hepatic enzymes (aspartate aminotransferase
[AST] and alanine aminotransferase [ALT]), total bilirubin (unless the Investigator has
evidence that increased indirect bilirubin corresponds to a Gilbert*s-type syndrome) that
exceed 1.5 x the upper limit of normal (1.5 x ULN), or any laboratory findings showing
evidence of organ dysfunction or any clinically significant deviation from the normal
range, as decided by the Investigator at the screening visit
3. Any clinically significant physical exam abnormalities observed during the screening
visit
4. Any gross mechanical nasal obstruction, or history of nasal or sinus surgery that may interfere with the conduct of the NAC as per judgment of the Investigator.
5. Use of any concomitant medications within 3 weeks of the screening visit including
antihistamines, leukotriene inhibitors, mast cell inhibitors, topical corticosteroids
including intranasal corticosteroids, oral or topical decongestants, topical calcineurin
inhibitors, beta blockers, nutritional supplements, over-the-counter medications, and use
of systemic corticosteroids within 12 weeks.
6. Use of anti-IgE therapy within 6 months prior to screening.
7. History of SIT with cat allergen and vaccines against cat allergy
8. SIT with any allergen within 3 months prior to screening
9. Habitation in a household with 1 or more cats or chronic exposure to cats within
3 months prior to the screening visit and during the duration of the study
10. Subjects with grass, tree, or Artemesia sensitization (confirmed at screening by both a
positive skin prick test and a positive allergen-specific IgE test [> 0.35 kAU/l] for
respective allergens) may only be enrolled at the end of regional pollen season and at the
discretion of the investigator. Note: In view of regional variations on allergen exposure,
the appropriate seasonal allergen will be tested.
11. Subjects who anticipate major changes in allergen exposure in their home or work environments during the course of the study as assessed by the Investigator.
12. Subjects receiving therapy with any agents known or likely to interact with adrenaline
(eg, beta blockers, ACE-inhibitors, tri-cyclic antidepressants, or other drugs), within
3 weeks prior to screening
13. Hospitalization for any reason within 30 days of the screening visit
14. Asthma requiring chronic treatment (except asthma subjects treated with intermittent
salbutamol) or atopic dermatitis requiring treatment with topical or systemic
corticosteroids and/or calcineurin inhibitors within 6 months prior to screening
15. Human immunodefieciency virus (HIV) infection or HIV seropositivity at the screening
visit
16. Positive hepatitis B surface antigen (HBsAg) or hepatitis C antibody at the screening visit
17. Known sensitivity to doxycycline or to any of the components of the Investigational
Product formulation
18. History of severe asthmatic reaction or anaphylaxis after exposure to cats
19. Participation in any clinical research study evaluating another investigational drug or
therapy within 90 days or at least 5 half-lives (whichever

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Change in TNSS AUC between day 8 and pretreatment NAC over the first hour of<br /><br>the challenge (0 hour to hour 1).</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>- Change from pretreatment NAC to days 29, 57, and 85 in TNSS AUC over the<br /><br>first hour of the initial challenge (0 hour to hour 1)<br /><br>- Change from pretreatment NAC to days 8, 29, 57, and 85 in TNSS AUC during<br /><br>hour 1 to hour 8 of the initial challenge<br /><br>- Incidence rates of treatment-emergent adverse events (TEAEs) and serious<br /><br>TEAEs through day 85 in subjects treated with a single 600 mg SC dose of<br /><br>REGN1908-1909 or placebo<br /><br>- Characterization of the key PK parameters of REGN1908 and REGN1909 following<br /><br>SC coadministration at a 1:1 ratio.</p><br>