Seasonal Allergic Rhinitis
Conditions
Brief summary
This study is a proof-of-concept study to demonstrate if a daily dose of a 2-days pre-treatment of Fexofenadine 180mg is effective in alleviating the AR symptoms and to assess the additional benefit to the patient in terms of preventing Allergic Rhinitis (AR) symptoms. The total study duration per participant is expected at least 4 months, depending on the timing of the screening visit. 5 visits are planned, screening, confirmation inclusion challenge, randomization visit, challenge and end of study visit.
Detailed description
The end of the study is defined as the date of the last visit of the last participant in the study. A participant is considered to have completed the study if he/she has completed all visits of the study including Visit 5 (Day 5).
Interventions
DRUGFexofenadine
Fexofenadine oral tablet
DRUGPlacebo
Fexofenadine matching placebo oral tablet
Sponsors
Opella Healthcare Group SAS, a Sanofi Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Participants are eligible to be included in the study only if all of the following criteria apply: * Participant is willing to provide written informed consent. * Adult participants (18 to 80 years old) suffering from seasonal allergic rhinitis (SAR) provoked by Ragweed pollen. * Participants having a total nasal symptom score (TNSS)-3 ≥4 (with 3 nasal symptoms) at first pollen challenge at Visit 2. * Having a 2-year history of SAR with Positive skin prick test to Ragweed allergen at screening (with a wheal diameter at least 3 mm larger than that produced by the negative control).
Exclusion criteria
* History of anaphylaxis to Ragweed pollen History of asthma or exacerbations in the past 12 months requiring regular inhaled corticosteroids for greater than 4 weeks per year, any oral corticosteroid usage, any emergency department visit for asthma or any asthma-related hospitalization. Mild asthmatics treated only with pro re nata short-acting β2agonists, less than 2 doses per week can be enrolled. * History of chronic sinusitis, defined as a sinus symptoms lasting greater than 12 weeks that includes 2 or more major factors or 1 major factor and 2 minor factors. Major factors are defined as facial pain or pressure, nasal obstruction or blockage, nasal discharge or purulence or discolored postnasal discharge, purulence in nasal cavity, or impaired or loss of smell. Minor factors are defined as headache, fever, halitosis, fatigue, dental pain, cough, and ear pain, pressure, or fullness. * History of systemic disease affecting the immune system such as autoimmune diseases, immune complex disease, or immunodeficiency, where, in the opinion of the study physician, participation in the trial would pose a risk or significant effect on the immune system. * Presence or history of drug hypersensitivity to fexofenadine and/or its excipients. * Participants unable to stop the following forbidden treatments/nutriments prior to pollen challenge: * Antihistamines: within 3 days for first-generation antihistamines, within 2 days for second-generation antihistamines. * Intranasal or inhaled corticosteroids: 7 days. * Ocular, intranasal, or inhaled sodium cromoglycate: 14 days. * High doses of systemic corticosteroids: 30 days. * Leukotriene antagonists: 30 days. * Intranasal or systemic decongestants: 3 days. * Tricyclic antidepressants: 7 days. * Any citrus fruits (grapefruit, orange, etc.) or their juices, as well as all fruit juices: 5 days. * Aluminum-and-magnesium containing antacids: 7 days. * Omalizumab/dupilumab: within 6 months * Any contraindications to fexofenadine, according to the labeling. * The above information is not intended to contain all considerations relevant to a potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under Curve (AUC) of the Total Nasal Symptoms Score (TNSS-3) | From 0 hour to 6 hours at Day 4 | TNSS-3=composite score calculated as sum of rhinorrhea, sneezing, and nasal itching scores (TNSS-3: scale of each symptom is scored from 0 to 3), where 0 indicates no symptoms, a score of 1 for mild symptoms that are easily tolerated, 2 for awareness of symptoms which are bothersome but tolerable and 3 is reserved for severe symptoms that are hard to tolerate and interfere with daily activity. Individual scores were collected in e-diary. AUC of TNSS from time of the first observation to time of the last observation (AUC \[0-6 hr\]) was calculated by using the linear trapezoid method. Trapezoidal rule involves dividing the area into a number of strips of equal width. Then, approximating the area of each strip by the area of the trapezium formed when a chord replaces upper end. Sum of these approximations gives final numerical result of area under the curve. AUC range: Arm A=0.0-43.5; Arm B=2.1-39.9. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUC of Total Nasal Symptoms Score (TNSS-3) (H0-H12 at Day 4) | From 0 hour to 12 hours at Day 4 | TNSS-3=composite score calculated as sum of rhinorrhea, sneezing, and nasal itching scores (TNSS-3: scale of each symptom is scored from 0 to 3), where 0 indicates no symptoms, a score of 1 for mild symptoms that are easily tolerated, 2 for awareness of symptoms which are bothersome but tolerable and 3 is reserved for severe symptoms that are hard to tolerate and interfere with daily activity. Individual scores were collected in e-diary. AUC of TNSS from time of the first observation to time of the last observation (AUC \[0-12 hr\]) was calculated by using the linear trapezoid method. Trapezoidal rule involves dividing the area into a number of strips of equal width. Then, approximating the area of each strip by the area of the trapezium formed when a chord replaces upper end. Sum of these approximations gives final numerical result of area under the curve. AUC range: Arm A=0.0-63.5; Arm B=2.1-69.4. |
| AUC of Total Ocular Symptoms Score (TOSS) (H0-H12 at Day 4) | From 0 hour to 12 hours at Day 4 | TOSS=composite score calculated as the sum of red/burning eyes, tearing, itchy/watery eyes scores (TOSS: scale of each symptom is scored from 0 to 3), where 0 indicates no symptoms, a score of 1 for mild symptoms that are easily tolerated, 2 for awareness of symptoms which are bothersome but tolerable and 3 is reserved for severe symptoms that are hard to tolerate and interfere with daily activity. individual scores were collected in e-diary. AUC of TOSS from time of the first observation to time of the last observation (AUC \[0-12 hr\]) was calculated by using the linear trapezoid. Trapezoidal rule involves dividing the area into a number of strips of equal width. Then, approximating the area of each strip by the area of the trapezium formed when a chord replaces upper end. Sum of these approximations gives final numerical result of area under the curve. AUC range: Arm A=0.0-58.6; Arm B=0.0-65.5. |
| AUC of Total Ocular Symptoms Score (TOSS) (H0-H6 at Day 4) | From 0 hour to 6 hours at Day 4 | TOSS=composite score calculated as the sum of red/burning eyes, tearing, itchy/watery eyes scores (TOSS: scale of each symptom is scored from 0 to 3), where 0 indicates no symptoms, a score of 1 for mild symptoms that are easily tolerated, 2 for awareness of symptoms which are bothersome but tolerable and 3 is reserved for severe symptoms that are hard to tolerate and interfere with daily activity. individual scores were collected in e-diary. AUC of TOSS from time of the first observation to time of the last observation (AUC \[0-6 hr\]) was calculated by using the linear trapezoid. Trapezoidal rule involves dividing the area into a number of strips of equal width. Then, approximating the area of each strip by the area of the trapezium formed when a chord replaces upper end. Sum of these approximations gives final numerical result of area under the curve. AUC range: Arm A=0.0-43.6; Arm B=0.0-35.1. |
| AUC of Total Ocular Symptoms Score (TOSS) (Day 1 to Day 4) | From randomization (Day 1) to Day 4 | TOSS=composite score calculated as the sum of red/burning eyes, tearing, itchy/watery eyes scores (TOSS: scale of each symptom is scored from 0 to 3), where 0 indicates no symptoms, a score of 1 for mild symptoms that are easily tolerated, 2 for awareness of symptoms which are bothersome but tolerable and 3 is reserved for severe symptoms that are hard to tolerate and interfere with daily activity. individual scores were collected in e-diary. AUC of TOSS from time of the first observation to time of the last observation (AUC \[Day 1 to Day 4\]) was calculated by using the linear trapezoid. Trapezoidal rule involves dividing the area into a number of strips of equal width. Then, approximating the area of each strip by the area of the trapezium formed when a chord replaces upper end. Sum of these approximations gives final numerical result of area under the curve. AUC range: Arm A=0.0-226.6; Arm B=0.0-304.5. |
| Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) | From Day 2 to Day 5 | An adverse event (AE) is any symptom, sign, illness or experience that develops or worsens in severity during the course of the study. A treatment emergent adverse event (TEAE) is an event that emerges during treatment, having been absent pretreatment, or worsens relative to the pretreatment state. |
| AUC of Total Nasal Symptoms Score (TNSS-3) (Day 1 to Day 4) | From randomization (Day 1) to Day 4 | TNSS-3=composite score calculated as sum of rhinorrhea, sneezing, and nasal itching scores (TNSS-3:scale of each symptom is scored from 0 to 3), where 0 indicates no symptoms, a score of 1 for mild symptoms that are easily tolerated, 2 for awareness of symptoms which are bothersome but tolerable and 3 is reserved for severe symptoms that are hard to tolerate and interfere with daily activity. Individual scores were collected in e-diary. AUC of TNSS from time of the first observation to time of the last observation (AUC \[Day 1 to Day 4\]) was calculated by using the linear trapezoid method. Trapezoidal rule involves dividing the area into a number of strips of equal width. Then, approximating the area of each strip by the area of the trapezium formed when a chord replaces upper end. Sum of these approximations gives final numerical result of area under the curve. AUC range: Arm A=0.0-267.8; Arm B=2.1-379.0. |
Countries
Canada
Participant flow
Recruitment details
A total of 95 participants took part in the study at one investigative site in Canada from 23 January 2023 to 14 March 2023.
Pre-assignment details
Participants suffering from seasonal allergic rhinitis were randomly assigned in a 1:1 ratio to two arm groups Fexofenadine Pre-Treatment and Placebo Pre-Treatment.
Participants by arm
| Arm | Count |
|---|---|
| Arm A (Active-active) Two days of pre-treatment with Fexofenadine 180 mg each day in the morning on Day 2 and Day 3, then Fexofenadine180 mg after the pollen challenge on Day 4. | 47 |
| Arm B (Placebo-active) Two days of pre-treatment with tablet of matching placebo each day in the morning on Day 2 and Day 3, then Fexofenadine180 mg after the pollen challenge on Day 4. | 47 |
| Total | 94 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
Baseline characteristics
| Characteristic | Arm B (Placebo-active) | Total | Arm A (Active-active) |
|---|---|---|---|
| Age, Continuous | 44.7 years STANDARD_DEVIATION 13.05 | 45.9 years STANDARD_DEVIATION 12.92 | 47.0 years STANDARD_DEVIATION 12.82 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 46 Participants | 93 Participants | 47 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 5 Participants | 4 Participants |
| Race (NIH/OMB) White | 45 Participants | 86 Participants | 41 Participants |
| Sex: Female, Male Female | 34 Participants | 68 Participants | 34 Participants |
| Sex: Female, Male Male | 13 Participants | 26 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 47 | 0 / 47 |
| other Total, other adverse events | 9 / 47 | 6 / 47 |
| serious Total, serious adverse events | 0 / 47 | 0 / 47 |
Outcome results
Primary
Area Under Curve (AUC) of the Total Nasal Symptoms Score (TNSS-3)
TNSS-3=composite score calculated as sum of rhinorrhea, sneezing, and nasal itching scores (TNSS-3: scale of each symptom is scored from 0 to 3), where 0 indicates no symptoms, a score of 1 for mild symptoms that are easily tolerated, 2 for awareness of symptoms which are bothersome but tolerable and 3 is reserved for severe symptoms that are hard to tolerate and interfere with daily activity. Individual scores were collected in e-diary. AUC of TNSS from time of the first observation to time of the last observation (AUC \[0-6 hr\]) was calculated by using the linear trapezoid method. Trapezoidal rule involves dividing the area into a number of strips of equal width. Then, approximating the area of each strip by the area of the trapezium formed when a chord replaces upper end. Sum of these approximations gives final numerical result of area under the curve. AUC range: Arm A=0.0-43.5; Arm B=2.1-39.9.
Time frame: From 0 hour to 6 hours at Day 4
Population: The mITT analysis set contained all eligible, ITT, and treated participants with TNSS-3 evaluation at H0 at V4 and at least a further time point at Visit 4.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm A (Active-active) | Area Under Curve (AUC) of the Total Nasal Symptoms Score (TNSS-3) | 16.96 Sum of scores*hours | Standard Deviation 9.09 |
| Arm B (Placebo-active) | Area Under Curve (AUC) of the Total Nasal Symptoms Score (TNSS-3) | 21.42 Sum of scores*hours | Standard Deviation 10.431 |
p-value: 0.03895% CI: [-8.24, -0.23]ANCOVA
Secondary
AUC of Total Nasal Symptoms Score (TNSS-3) (Day 1 to Day 4)
TNSS-3=composite score calculated as sum of rhinorrhea, sneezing, and nasal itching scores (TNSS-3:scale of each symptom is scored from 0 to 3), where 0 indicates no symptoms, a score of 1 for mild symptoms that are easily tolerated, 2 for awareness of symptoms which are bothersome but tolerable and 3 is reserved for severe symptoms that are hard to tolerate and interfere with daily activity. Individual scores were collected in e-diary. AUC of TNSS from time of the first observation to time of the last observation (AUC \[Day 1 to Day 4\]) was calculated by using the linear trapezoid method. Trapezoidal rule involves dividing the area into a number of strips of equal width. Then, approximating the area of each strip by the area of the trapezium formed when a chord replaces upper end. Sum of these approximations gives final numerical result of area under the curve. AUC range: Arm A=0.0-267.8; Arm B=2.1-379.0.
Time frame: From randomization (Day 1) to Day 4
Population: The mITT analysis set contained all eligible, ITT, and treated participants with TNSS-3 evaluation at H0 at V4 and at least a further time point at Visit 4.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm A (Active-active) | AUC of Total Nasal Symptoms Score (TNSS-3) (Day 1 to Day 4) | 56.34 Sum of scores*hours | Standard Deviation 55.697 |
| Arm B (Placebo-active) | AUC of Total Nasal Symptoms Score (TNSS-3) (Day 1 to Day 4) | 65.48 Sum of scores*hours | Standard Deviation 76.454 |
p-value: 0.07495% CI: [-38.74, 1.83]ANCOVA
Secondary
AUC of Total Nasal Symptoms Score (TNSS-3) (H0-H12 at Day 4)
TNSS-3=composite score calculated as sum of rhinorrhea, sneezing, and nasal itching scores (TNSS-3: scale of each symptom is scored from 0 to 3), where 0 indicates no symptoms, a score of 1 for mild symptoms that are easily tolerated, 2 for awareness of symptoms which are bothersome but tolerable and 3 is reserved for severe symptoms that are hard to tolerate and interfere with daily activity. Individual scores were collected in e-diary. AUC of TNSS from time of the first observation to time of the last observation (AUC \[0-12 hr\]) was calculated by using the linear trapezoid method. Trapezoidal rule involves dividing the area into a number of strips of equal width. Then, approximating the area of each strip by the area of the trapezium formed when a chord replaces upper end. Sum of these approximations gives final numerical result of area under the curve. AUC range: Arm A=0.0-63.5; Arm B=2.1-69.4.
Time frame: From 0 hour to 12 hours at Day 4
Population: The mITT analysis set contained all eligible, ITT, and treated participants with TNSS-3 evaluation at H0 at V4 and at least a further time point at Visit 4.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm A (Active-active) | AUC of Total Nasal Symptoms Score (TNSS-3) (H0-H12 at Day 4) | 23.66 Sum of scores*hours | Standard Deviation 14.049 |
| Arm B (Placebo-active) | AUC of Total Nasal Symptoms Score (TNSS-3) (H0-H12 at Day 4) | 31.01 Sum of scores*hours | Standard Deviation 18.555 |
p-value: 0.04895% CI: [-12.95, -0.05]ANCOVA
Secondary
AUC of Total Ocular Symptoms Score (TOSS) (Day 1 to Day 4)
TOSS=composite score calculated as the sum of red/burning eyes, tearing, itchy/watery eyes scores (TOSS: scale of each symptom is scored from 0 to 3), where 0 indicates no symptoms, a score of 1 for mild symptoms that are easily tolerated, 2 for awareness of symptoms which are bothersome but tolerable and 3 is reserved for severe symptoms that are hard to tolerate and interfere with daily activity. individual scores were collected in e-diary. AUC of TOSS from time of the first observation to time of the last observation (AUC \[Day 1 to Day 4\]) was calculated by using the linear trapezoid. Trapezoidal rule involves dividing the area into a number of strips of equal width. Then, approximating the area of each strip by the area of the trapezium formed when a chord replaces upper end. Sum of these approximations gives final numerical result of area under the curve. AUC range: Arm A=0.0-226.6; Arm B=0.0-304.5.
Time frame: From randomization (Day 1) to Day 4
Population: The mITT analysis set contained all eligible, ITT, and treated participants with TNSS-3 evaluation at H0 at V4 and at least a further time point at Visit 4.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm A (Active-active) | AUC of Total Ocular Symptoms Score (TOSS) (Day 1 to Day 4) | 39.51 Sum of scores*hours | Standard Deviation 55.416 |
| Arm B (Placebo-active) | AUC of Total Ocular Symptoms Score (TOSS) (Day 1 to Day 4) | 47.21 Sum of scores*hours | Standard Deviation 69.443 |
p-value: 0.72995% CI: [-27.24, 19.12]ANCOVA
Secondary
AUC of Total Ocular Symptoms Score (TOSS) (H0-H12 at Day 4)
TOSS=composite score calculated as the sum of red/burning eyes, tearing, itchy/watery eyes scores (TOSS: scale of each symptom is scored from 0 to 3), where 0 indicates no symptoms, a score of 1 for mild symptoms that are easily tolerated, 2 for awareness of symptoms which are bothersome but tolerable and 3 is reserved for severe symptoms that are hard to tolerate and interfere with daily activity. individual scores were collected in e-diary. AUC of TOSS from time of the first observation to time of the last observation (AUC \[0-12 hr\]) was calculated by using the linear trapezoid. Trapezoidal rule involves dividing the area into a number of strips of equal width. Then, approximating the area of each strip by the area of the trapezium formed when a chord replaces upper end. Sum of these approximations gives final numerical result of area under the curve. AUC range: Arm A=0.0-58.6; Arm B=0.0-65.5.
Time frame: From 0 hour to 12 hours at Day 4
Population: The mITT analysis set contained all eligible, ITT, and treated participants with TNSS-3 evaluation at H0 at V4 and at least a further time point at Visit 4.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm A (Active-active) | AUC of Total Ocular Symptoms Score (TOSS) (H0-H12 at Day 4) | 14.74 Sum of scores*hours | Standard Deviation 14.432 |
| Arm B (Placebo-active) | AUC of Total Ocular Symptoms Score (TOSS) (H0-H12 at Day 4) | 21.67 Sum of scores*hours | Standard Deviation 17.154 |
p-value: 0.01195% CI: [-13.21, -1.73]ANCOVA
Secondary
AUC of Total Ocular Symptoms Score (TOSS) (H0-H6 at Day 4)
TOSS=composite score calculated as the sum of red/burning eyes, tearing, itchy/watery eyes scores (TOSS: scale of each symptom is scored from 0 to 3), where 0 indicates no symptoms, a score of 1 for mild symptoms that are easily tolerated, 2 for awareness of symptoms which are bothersome but tolerable and 3 is reserved for severe symptoms that are hard to tolerate and interfere with daily activity. individual scores were collected in e-diary. AUC of TOSS from time of the first observation to time of the last observation (AUC \[0-6 hr\]) was calculated by using the linear trapezoid. Trapezoidal rule involves dividing the area into a number of strips of equal width. Then, approximating the area of each strip by the area of the trapezium formed when a chord replaces upper end. Sum of these approximations gives final numerical result of area under the curve. AUC range: Arm A=0.0-43.6; Arm B=0.0-35.1.
Time frame: From 0 hour to 6 hours at Day 4
Population: The mITT analysis set contained all eligible, ITT, and treated participants with TNSS-3 evaluation at H0 at V4 and at least a further time point at Visit 4.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm A (Active-active) | AUC of Total Ocular Symptoms Score (TOSS) (H0-H6 at Day 4) | 11.74 Sum of scores*hours | Standard Deviation 10.451 |
| Arm B (Placebo-active) | AUC of Total Ocular Symptoms Score (TOSS) (H0-H6 at Day 4) | 16.21 Sum of scores*hours | Standard Deviation 11.253 |
p-value: 0.02595% CI: [-8.9, -0.6]ANCOVA
Secondary
Percentage of Participants With Treatment Emergent Adverse Events (TEAEs)
An adverse event (AE) is any symptom, sign, illness or experience that develops or worsens in severity during the course of the study. A treatment emergent adverse event (TEAE) is an event that emerges during treatment, having been absent pretreatment, or worsens relative to the pretreatment state.
Time frame: From Day 2 to Day 5
Population: The SAF set contained all participants in the ITT set who received at least one dose of study drug and participants were classified according to treatment received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A (Active-active) | Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) | 19.1 percentage of participants |
| Arm B (Placebo-active) | Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) | 12.8 percentage of participants |