A Study To Assess The Safety And Tolerability Of Different Doses Of PF-06444753 And PF-06444752 In Subjects With Allergic Rhinitis

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety and tolerability of different doses of PF-06444753 and PF-06444752 in subjects with allergic rhinitis.

Official Title
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A Phase 1, Randomized, Double Blinded, Placebo Controlled Study To Evaluate The Safety, Tolerability, Immunogenicity, And Exploratory Pharmacodynamic Response Of Ascending Dose Levels Of An Anti-ige Vaccine With Two Different Adjuvant Formulations (Pf-06444753 And Pf-06444752) In Generally Healthy Subjects With Allergic Rhinitis

Conditions
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Allergic Rhinitis

Intervention / Treatment
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* Biological: IGE-1
* Biological: IGE-2
* Biological: Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy, males or females of non-child bearing potential, who are between 18 and 55 years, inclusive, Intermittent or persistent allergic rhinitis that is associated with perennial or seasonal allergen reactivity at screening as determined by a positive specific IgE level ≥1 KU/L to at least one of the following common allergens: dust mite (Dermatophagoides farinae or Dermatophagoides pteronyssinus), cat, dog, mold (Alternaria), Bermuda grass, common ragweed, oak, Timothy grass or elm. Exclusion Criteria: Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, or neurologic disease that may compromise their ability to safely participate in the study. Evidence or history of clinically significant pulmonary disease (including allergic and non-allergic asthma, chronic obstructive pulmonary disease [COPD], cystic fibrosis, bronchiectasis, chronic bronchitis, emphysema, tuberculosis, pulmonary fibrosis, pulmonary hypertension, or others). Evidence or history of clinically significant autoimmune disease (including rheumatoid arthritis, systemic lupus erythematosus, ulcerative colitis, or others).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PF-06444753<br> | Biological: IGE-1<br>* Intramuscular, multiple dose<br>|
| Experimental: PF-06444752<br> | Biological: IGE-2<br>* Intramuscular, multiple dose<br>|
| Placebo Comparator: Placebo<br>Intramuscular | Biological: Saline<br>* Saline (0.9% sodium chloride)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentages of Participants With Local Reactions By Severity Within 14 Days of Any Vaccination | Local reactions consisted of any pain at the site of injection, any swelling, and any redness. Participants were issued an electronic diary (e-diary) and were asked to monitor and record (according to corresponding grading scales) any local reactions for 14 days following each vaccination. Grading details are as follows: Mild (Pain: did not interfere with activity; Redness and Swelling: 0.5-5.0 centimeters [cm] or 1-10 caliper units), Moderate (Pain: interfered with activity; Redness and Swelling: more than [>] 5.0 to 10.0 cm or 11-20 caliper units), Severe (Pain: prevented daily activity; Redness and Swelling: >10 cm or 21 caliper units and above). | Within 14 days | 
| Percentages of Participants With Systemic Reactions By Severity Within 14 Days of Any Vaccination | Systemic reactions consisted of fever, vomiting, diarrhea, headache, fatigue, muscle pain (other than at the injection site) and joint pain (other than pain adjacent to injection site). Participants were issued an electronic diary (e-diary) and were asked to monitor and record (according to corresponding grading scales) any systemic reactions for 14 days following each vaccination. Grading details are as follows: Mild (Vomiting: 1-2 times in 24 hours; Diarrhea: 2-3 loose stools in 24 hours; Headache, Fatigue, Muscle Pain, Joint Pain: no interference with activity), Moderate (Vomiting: >2 times in 24 hours; Diarrhea: 4-5 loose stools in 24 hours; Headache, Fatigue, Muscle and Joint Pain: some interference with activity), Severe (Vomiting: required intravenous hydration; Diarrhea: more than or equal to [>=] 6 stool in 24 hours; Headache, Fatigue, Muscle and Joint Pain: Significant, prevented daily activity). | Within 14 days | 
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations From Treatment Due to TEAEs | An adverse event (AE) was any untoward medical occurrence attributed to study drug in a participant who received study drug. AEs comprised both SAEs and non-SAEs. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Severe TEAEs were those that interfered significantly with the participant's usual function. Causality assessment was made by the investigator. | Baseline up to 336 days post study administration or at Early Termination | 
| Number of Participants With Laboratory Test Abnormalities | Number of participants with laboratory test abnormalities without regard to baseline abnormality. Laboratory test parameters included hematology, coagulation, liver function, renal function, electrolytes, hormones, clinical chemistry, immunology urinalysis, urinalysis (dipstick and microscopy), and other tests such as human immunodeficiency virus antibody and hepatitis C antibody. | Baseline up to 336 days post last study drug administration or Early Termination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Enzyme-Linked Immunosorbent Assay (ELISA) Measured Anti-IgE Geometric Mean Titers (GMTs) at Baseline, Day 182, and Day 336 | Ability of vaccine induced serum anti-immunoglobulin E (IgE) antibodies to interfere with IgE binding to recombinant alpha chain of the high affinity IgE receptor was assessed in an ELISA based assay. GMTs were calculated both as crude means (unadjusted) and by an analysis of covariance (ANCOVA) model with natural log transformed antibody titer as outcome variable, and treatment group as factor and baseline (in log scale) as covariates at each of the post dose measurement. | Baseline (Day 1), Day 182 (2 weeks after last vaccination), and end of study (Day 336) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vaccines, Phase 1, Allergic Rhinitis