Perennial Allergic Rhinitis, Rhinitis, Allergic
Conditions
Keywords
Allergic rhinitis symptoms, Runny nose, Itchy nose
Brief summary
Alleviation of allergic symptoms induced by house dust mites when using the medical device AM-301. This clinical investigation explored the efficacy and safety of AM-301 when used to reduce symptoms of house dust mite sufferers. The primary objective was to compare the efficacy of AM-301 Device between treated and non-treated subjects in the treatment of perennial allergic rhinitis (PAR).
Detailed description
This was a randomized, open-label, 3-period crossover study. The total study duration was approximately 65 days and consisted of 2 screening visits and 3 treatment visits (total 5 visits) followed by a telephone call. Patients with HDM allergy as assessed by their medical history and a positive skin prick test for Dermatophagoides pteronyssinus (der p) allergen were enrolled into the screening phase. At least 7 days after the second screening visit, the treatment visits started. Eligible subjects were randomized to one of the six treatment sequences (ABC, BCA, CAB, ACB, BAC, CBA) at an equal ratio. The treatments were applied 10 minutes before the challenge at Visit 3, 4 and 5: * Treatment A: One spray AM-301 (0.14 mL) per nostril, * Treatment B: Two sprays AM-301 (0.28 mL) per nostril (at two defined spray angles in order to obtain a broader coverage of the nasal mucosa), * Treatment C: no treatment. The cross-over design allowed treatment C to be used as internal control. Between the three treatment visits in the chamber there was a 7±2 days wash-out period.
Interventions
DEVICETreatment A
Nasal Spray with drug-free aqueous gel emulsion (AM-301) intended to help protect against airborne allergens. One Spray of AM-301 per nostril
DEVICETreatment B
Nasal Spray with drug-free aqueous gel emulsion (AM-301) intended to help protect against airborne allergens. Two Sprays of AM-301 per nostril (with different spray angles)
OTHERTreatment C
No treatment
Sponsors
Altamira Medica Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Main Inclusion Criteria: * Body mass index between 18.0 and 32.0 kg/m2 inclusive. * History of perennial allergic rhinitis to house dust mite for more than 1 year. * Positive Skin Prick Test (SPT) for Dermatophagoides pteronyssinus (der p) allergen at screening or within 12 months prior to the screening visit. Main
Exclusion criteria
* Any clinically relevant abnormal findings in physical examination, clinical chemistry, hematology, urinalysis, vital signs, lung function at screening visit, which, in the opinion of the investigator, may either put the subject at risk because of participation in the study or may influence the results of the study, or the subject's ability to participate in the study. * Use of any medication considered to have an influence on the outcome of the study during the EEC session, at the discretion of the Investigator and/or designee. * Recent nasal ulcers, mucosal erosion, nasal surgery, or nasal trauma, that might interfere with study results as determined by the Investigator and/or designee.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Change From Baseline in TNSS at Visits 3, 4 and 5 | Day 8 to Day 22 | Total Nasal Symptom Score (TNSS) average from 20 - 180 minutes will be compared between treated and non-treated subjects. Data from all three visits are combined. Scale for a single symptom is from 0 - 3, 0 meaning no symptoms and 3 severe symptoms. Assessed symptoms are: nasal congestion, runny nose, nasal itching and sneezing. TNSS is the sum of the rating of all 4 symptoms and ranges from 0-12. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Difference of Total Nasal Symptom Score (TNSS) at Individual Timepoints During House Dust Mite Challenge in the EEC (0-180 Min) Between Single and Double Application of AM-301 and no Treatment. | Day 8 to Day 22 | Total Nasal Symptom Score (TNSS) average from 20 - 180 min was compared between treated and non-treated subjects. Scale for a single symptom is from 0 - 3, 0 meaning no symptoms and 3 severe symptoms. Assessed symptoms are: nasal congestion, runny nose, nasal itching and sneezing. TNSS is the sum of the rating of all 4 symptoms and ranges from 0-12. This descriptive endpoint was not corrected for baseline. |
Countries
Canada
Participant flow
Recruitment details
The study was conducted from November 10, 2021 (first subject first screening) to April 04, 2022 (last subject telephone call). Details on treatment sequences: Subjects that qualified for randomization, could enter the treatment period where they received a treatment before entering the chamber. This treatment could be either A - one spray of AM-301 per nostril, B - two sprays of AM-301 per nostril or C - no treatment at all. The order of the treatments was different \> sequences (ABC, xxx).
Pre-assignment details
Patients with house dust mite (HDM) allergy as assessed by their medical history and a positive skin prick test for Dermatophagoides pteronyssinus (der p) allergen were enrolled into the screening phase. 173 patients were screened and out of those, 37 patients were randomized into the prophylactic treatment phase with AM-301. Subjects that could not be enrolled mainly failed to show sufficient proof for HDM allergy.
Participants by arm
| Arm | Count |
|---|---|
| Sequence 1 Treatment sequence for the 3 treatment visits: ABC. | 6 |
| Sequence 2 Treatment sequence for the 3 treatment visits: BCA. | 6 |
| Sequence 3 Treatment sequence for the 3 treatment visits:CAB. | 6 |
| Sequence 4 Treatment sequence for the 3 treatment visits: ACB. | 6 |
| Sequence 5 Treatment sequence for the 3 treatment visits: BAC. | 7 |
| Sequence 6 Treatment sequence for the 3 treatment visits: CBA. | 6 |
| Total | 37 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Covid contact | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Protocol non-compliance | 0 | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Sequence 1 | Sequence 2 | Sequence 3 | Sequence 4 | Sequence 5 | Sequence 6 | Total |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 7 Participants | 6 Participants | 37 Participants |
| Age, Continuous | 33.5 years STANDARD_DEVIATION 8.34 | 44.8 years STANDARD_DEVIATION 14.44 | 28.3 years STANDARD_DEVIATION 4.84 | 40.7 years STANDARD_DEVIATION 9.54 | 35.4 years STANDARD_DEVIATION 10.45 | 31.7 years STANDARD_DEVIATION 6.74 | 35.7 years STANDARD_DEVIATION 10.47 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 2 Participants | 3 Participants | 2 Participants | 2 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 6 Participants | 4 Participants | 3 Participants | 5 Participants | 4 Participants | 27 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Canada | 6 participants | 6 participants | 6 participants | 6 participants | 7 participants | 6 participants | 37 participants |
| Sex: Female, Male Female | 6 Participants | 3 Participants | 3 Participants | 2 Participants | 6 Participants | 3 Participants | 23 Participants |
| Sex: Female, Male Male | 0 Participants | 3 Participants | 3 Participants | 4 Participants | 1 Participants | 3 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 36 | 0 / 37 | 0 / 36 |
| other Total, other adverse events | 4 / 36 | 0 / 37 | 0 / 36 |
| serious Total, serious adverse events | 0 / 36 | 0 / 37 | 0 / 36 |
Outcome results
Primary
Overall Change From Baseline in TNSS at Visits 3, 4 and 5
Total Nasal Symptom Score (TNSS) average from 20 - 180 minutes will be compared between treated and non-treated subjects. Data from all three visits are combined. Scale for a single symptom is from 0 - 3, 0 meaning no symptoms and 3 severe symptoms. Assessed symptoms are: nasal congestion, runny nose, nasal itching and sneezing. TNSS is the sum of the rating of all 4 symptoms and ranges from 0-12.
Time frame: Day 8 to Day 22
Population: All participants received all three treatments in a different order (sequence). Therefore, data are available for each treatment for all participants. In the ITT population, all participants of the safety population with at least one TNSS assessment are included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Overall Change From Baseline in TNSS at Visits 3, 4 and 5 | 3.9 TNSS score (0-12) | Standard Deviation 2.59 |
| Treatment B | Overall Change From Baseline in TNSS at Visits 3, 4 and 5 | 4.1 TNSS score (0-12) | Standard Deviation 2.93 |
| Treatment C | Overall Change From Baseline in TNSS at Visits 3, 4 and 5 | 5.2 TNSS score (0-12) | Standard Deviation 2.58 |
Comparison: Treatment A + B were pooled to Treatment D for the Primary endpoint. The primary objective was to compare the efficacy of the AM-301 nasal spray (treatment D= A+B) and no treatment (C) in reducing nasal symptoms induced from HDM allergen exposure.~The TNSS value from the baseline exposure (at screening exposure visit 2) was subtracted from the TNSS value of the treatment exposure to obtain change from baseline. A lower value resembles less symptoms.p-value: 0.0085ANCOVA
Secondary
Difference of Total Nasal Symptom Score (TNSS) at Individual Timepoints During House Dust Mite Challenge in the EEC (0-180 Min) Between Single and Double Application of AM-301 and no Treatment.
Total Nasal Symptom Score (TNSS) average from 20 - 180 min was compared between treated and non-treated subjects. Scale for a single symptom is from 0 - 3, 0 meaning no symptoms and 3 severe symptoms. Assessed symptoms are: nasal congestion, runny nose, nasal itching and sneezing. TNSS is the sum of the rating of all 4 symptoms and ranges from 0-12. This descriptive endpoint was not corrected for baseline.
Time frame: Day 8 to Day 22
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A | Difference of Total Nasal Symptom Score (TNSS) at Individual Timepoints During House Dust Mite Challenge in the EEC (0-180 Min) Between Single and Double Application of AM-301 and no Treatment. | 140 min in chamber | 4.4 TNSS (0-12) | Standard Deviation 3 |
| Treatment A | Difference of Total Nasal Symptom Score (TNSS) at Individual Timepoints During House Dust Mite Challenge in the EEC (0-180 Min) Between Single and Double Application of AM-301 and no Treatment. | 100 min in chamber | 4.2 TNSS (0-12) | Standard Deviation 2.99 |
| Treatment A | Difference of Total Nasal Symptom Score (TNSS) at Individual Timepoints During House Dust Mite Challenge in the EEC (0-180 Min) Between Single and Double Application of AM-301 and no Treatment. | 60 min in chamber | 4.6 TNSS (0-12) | Standard Deviation 2.79 |
| Treatment A | Difference of Total Nasal Symptom Score (TNSS) at Individual Timepoints During House Dust Mite Challenge in the EEC (0-180 Min) Between Single and Double Application of AM-301 and no Treatment. | 40 min in chamber | 3.6 TNSS (0-12) | Standard Deviation 2.71 |
| Treatment A | Difference of Total Nasal Symptom Score (TNSS) at Individual Timepoints During House Dust Mite Challenge in the EEC (0-180 Min) Between Single and Double Application of AM-301 and no Treatment. | 80 min in chamber | 4.3 TNSS (0-12) | Standard Deviation 3.05 |
| Treatment A | Difference of Total Nasal Symptom Score (TNSS) at Individual Timepoints During House Dust Mite Challenge in the EEC (0-180 Min) Between Single and Double Application of AM-301 and no Treatment. | 160 min in chamber | 4.1 TNSS (0-12) | Standard Deviation 3.33 |
| Treatment A | Difference of Total Nasal Symptom Score (TNSS) at Individual Timepoints During House Dust Mite Challenge in the EEC (0-180 Min) Between Single and Double Application of AM-301 and no Treatment. | Pre-chamber | 0.1 TNSS (0-12) | Standard Deviation 0.35 |
| Treatment A | Difference of Total Nasal Symptom Score (TNSS) at Individual Timepoints During House Dust Mite Challenge in the EEC (0-180 Min) Between Single and Double Application of AM-301 and no Treatment. | 180 min in chamber | 4.3 TNSS (0-12) | Standard Deviation 3.51 |
| Treatment A | Difference of Total Nasal Symptom Score (TNSS) at Individual Timepoints During House Dust Mite Challenge in the EEC (0-180 Min) Between Single and Double Application of AM-301 and no Treatment. | 120 min in chamber | 4.5 TNSS (0-12) | Standard Deviation 3.06 |
| Treatment A | Difference of Total Nasal Symptom Score (TNSS) at Individual Timepoints During House Dust Mite Challenge in the EEC (0-180 Min) Between Single and Double Application of AM-301 and no Treatment. | 20 min in chamber | 2.3 TNSS (0-12) | Standard Deviation 2.42 |
| Treatment B | Difference of Total Nasal Symptom Score (TNSS) at Individual Timepoints During House Dust Mite Challenge in the EEC (0-180 Min) Between Single and Double Application of AM-301 and no Treatment. | 160 min in chamber | 4.9 TNSS (0-12) | Standard Deviation 3.8 |
| Treatment B | Difference of Total Nasal Symptom Score (TNSS) at Individual Timepoints During House Dust Mite Challenge in the EEC (0-180 Min) Between Single and Double Application of AM-301 and no Treatment. | 40 min in chamber | 3.6 TNSS (0-12) | Standard Deviation 2.85 |
| Treatment B | Difference of Total Nasal Symptom Score (TNSS) at Individual Timepoints During House Dust Mite Challenge in the EEC (0-180 Min) Between Single and Double Application of AM-301 and no Treatment. | Pre-chamber | 0.1 TNSS (0-12) | Standard Deviation 0.49 |
| Treatment B | Difference of Total Nasal Symptom Score (TNSS) at Individual Timepoints During House Dust Mite Challenge in the EEC (0-180 Min) Between Single and Double Application of AM-301 and no Treatment. | 20 min in chamber | 2.4 TNSS (0-12) | Standard Deviation 2.64 |
| Treatment B | Difference of Total Nasal Symptom Score (TNSS) at Individual Timepoints During House Dust Mite Challenge in the EEC (0-180 Min) Between Single and Double Application of AM-301 and no Treatment. | 60 min in chamber | 3.6 TNSS (0-12) | Standard Deviation 3.04 |
| Treatment B | Difference of Total Nasal Symptom Score (TNSS) at Individual Timepoints During House Dust Mite Challenge in the EEC (0-180 Min) Between Single and Double Application of AM-301 and no Treatment. | 80 min in chamber | 4.3 TNSS (0-12) | Standard Deviation 3.18 |
| Treatment B | Difference of Total Nasal Symptom Score (TNSS) at Individual Timepoints During House Dust Mite Challenge in the EEC (0-180 Min) Between Single and Double Application of AM-301 and no Treatment. | 100 min in chamber | 4.7 TNSS (0-12) | Standard Deviation 3.4 |
| Treatment B | Difference of Total Nasal Symptom Score (TNSS) at Individual Timepoints During House Dust Mite Challenge in the EEC (0-180 Min) Between Single and Double Application of AM-301 and no Treatment. | 120 min in chamber | 4.8 TNSS (0-12) | Standard Deviation 3.67 |
| Treatment B | Difference of Total Nasal Symptom Score (TNSS) at Individual Timepoints During House Dust Mite Challenge in the EEC (0-180 Min) Between Single and Double Application of AM-301 and no Treatment. | 140 min in chamber | 5.1 TNSS (0-12) | Standard Deviation 3.69 |
| Treatment B | Difference of Total Nasal Symptom Score (TNSS) at Individual Timepoints During House Dust Mite Challenge in the EEC (0-180 Min) Between Single and Double Application of AM-301 and no Treatment. | 180 min in chamber | 5.1 TNSS (0-12) | Standard Deviation 3.81 |
| Treatment C | Difference of Total Nasal Symptom Score (TNSS) at Individual Timepoints During House Dust Mite Challenge in the EEC (0-180 Min) Between Single and Double Application of AM-301 and no Treatment. | 100 min in chamber | 6.5 TNSS (0-12) | Standard Deviation 3.08 |
| Treatment C | Difference of Total Nasal Symptom Score (TNSS) at Individual Timepoints During House Dust Mite Challenge in the EEC (0-180 Min) Between Single and Double Application of AM-301 and no Treatment. | Pre-chamber | 0.2 TNSS (0-12) | Standard Deviation 0.39 |
| Treatment C | Difference of Total Nasal Symptom Score (TNSS) at Individual Timepoints During House Dust Mite Challenge in the EEC (0-180 Min) Between Single and Double Application of AM-301 and no Treatment. | 160 min in chamber | 6.3 TNSS (0-12) | Standard Deviation 3.03 |
| Treatment C | Difference of Total Nasal Symptom Score (TNSS) at Individual Timepoints During House Dust Mite Challenge in the EEC (0-180 Min) Between Single and Double Application of AM-301 and no Treatment. | 120 min in chamber | 6.2 TNSS (0-12) | Standard Deviation 3.32 |
| Treatment C | Difference of Total Nasal Symptom Score (TNSS) at Individual Timepoints During House Dust Mite Challenge in the EEC (0-180 Min) Between Single and Double Application of AM-301 and no Treatment. | 20 min in chamber | 2.3 TNSS (0-12) | Standard Deviation 2.25 |
| Treatment C | Difference of Total Nasal Symptom Score (TNSS) at Individual Timepoints During House Dust Mite Challenge in the EEC (0-180 Min) Between Single and Double Application of AM-301 and no Treatment. | 60 min in chamber | 4.8 TNSS (0-12) | Standard Deviation 3.42 |
| Treatment C | Difference of Total Nasal Symptom Score (TNSS) at Individual Timepoints During House Dust Mite Challenge in the EEC (0-180 Min) Between Single and Double Application of AM-301 and no Treatment. | 180 min in chamber | 6.2 TNSS (0-12) | Standard Deviation 3.32 |
| Treatment C | Difference of Total Nasal Symptom Score (TNSS) at Individual Timepoints During House Dust Mite Challenge in the EEC (0-180 Min) Between Single and Double Application of AM-301 and no Treatment. | 80 min in chamber | 5.6 TNSS (0-12) | Standard Deviation 2.77 |
| Treatment C | Difference of Total Nasal Symptom Score (TNSS) at Individual Timepoints During House Dust Mite Challenge in the EEC (0-180 Min) Between Single and Double Application of AM-301 and no Treatment. | 40 min in chamber | 4.2 TNSS (0-12) | Standard Deviation 3.09 |
| Treatment C | Difference of Total Nasal Symptom Score (TNSS) at Individual Timepoints During House Dust Mite Challenge in the EEC (0-180 Min) Between Single and Double Application of AM-301 and no Treatment. | 140 min in chamber | 6.3 TNSS (0-12) | Standard Deviation 2.96 |