House Dust Mite Allergy, Rhinitis, Allergic, Perennial
Conditions
Brief summary
The objective of this study was to assess the efficacy and safety of 12 months of treatment with 300 IR of STG320 sublingual tablets compared with placebo in adults and adolescents with HDM-associated allergic rhinitis.
Detailed description
This study was a randomized, double-blind, placebo-controlled, phase III study with 2 parallel arms in adults and adolescents with HDM-associated allergic rhinitis (AR) for at least one year. The primary objective was to assess the efficacy of STG320 sublingual tablets at a daily dosage of 300 IR when administered for 12 months to adults and adolescents with HDM-associated AR. The primary efficacy variable was the average Total Combined Score.
Interventions
BIOLOGICAL300 IR
300 IR tablet of HDM Allergen Extracts
BIOLOGICALPlacebo
Placebo tablet
Sponsors
Stallergenes Greer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Main Inclusion Criteria: * Patients with HDM-associated allergic rhinitis (AR) for at least 1 year * Patients sensitized to D. pteronyssinus (D. pte) and/or D. farinae (D. far) defined on skin prick test and HDM-specific serum IgE Main
Exclusion criteria
* A history of rhinitis, rhinoconjunctivitis or asthma to allergens other than HDM, likely to result in rhinitis symptoms during the evaluation periods * Partly controlled or uncontrolled asthma * Controlled asthma requiring controller treatment(s) consistent with GINA 2014 treatment Steps 3 to 5
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Combined Score | 12 months | Average Total Combined Score (TCS), calculated for each patient as the average of the non-missing daily TCSs during the primary evaluation period. The daily TCS (scale 0-15) was the sum of the patient's daily Rhinitis Total Symptom Score (RTSS, scale 0-12) and daily Rescue Medication Score (RMS, scale 0-3). Lower is better. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Average Rhinitis Total Symptom Score (RTSS) | 12 months | Average RTSS during the primary evaluation period. The daily Total Symptom Scores (RTSS) was the sum of the 4 rhinitis symptom scores: sneezing, rhinorrhoea, nasal pruritus and nasal congestion, each graded on a 4-point scale (0-3; 0: absent, 1: mild, 2: moderate, 3: severe). It ranges from 0 to 12. Lower is better. |
| Average Rescue Medication Score (RMS) | 12 months | Average RMS during the primary evaluation period. Rescue Medication Score (RMS) ; range 0-3, lower is better. |
Countries
France, United States
Participant flow
Recruitment details
This study was conducted between 29 September 2015 (first patient, first visit) and 25 June 2018 (last patient, last visit).
Pre-assignment details
2,174 (50.9%) and 486 (11.4%) patients were excluded before and during the placebo run-in period, respectively. The main reason for screen failures at these two stages was a failure to meet randomization criteria.
Participants by arm
| Arm | Count |
|---|---|
| 300 IR 300 IR tablet of HDM Allergen Extracts | 711 |
| Placebo Placebo tablet | 765 |
| Total | 1,476 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 100 | 18 |
| Overall Study | Any other reason not above-mentioned | 3 | 2 |
| Overall Study | Lack of Efficacy | 1 | 1 |
| Overall Study | Lost to Follow-up | 19 | 14 |
| Overall Study | Non-compliance with study drug | 6 | 4 |
| Overall Study | Pregnancy | 6 | 5 |
| Overall Study | Protocol Violation | 2 | 4 |
| Overall Study | Withdrawal by parent/guardian | 3 | 5 |
| Overall Study | Withdrawal by Subject | 73 | 74 |
Baseline characteristics
| Characteristic | 300 IR | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 29.5 years STANDARD_DEVIATION 13.07 | 29.6 years STANDARD_DEVIATION 12.81 | 29.6 years STANDARD_DEVIATION 12.58 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 50 Participants | 96 Participants | 46 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 660 Participants | 1379 Participants | 719 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 21 Participants | 41 Participants | 20 Participants |
| Race (NIH/OMB) Black or African American | 25 Participants | 62 Participants | 37 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 5 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 4 Participants | 3 Participants |
| Race (NIH/OMB) White | 660 Participants | 1361 Participants | 701 Participants |
| Region of Enrollment Europe | 453 participants | 930 participants | 477 participants |
| Region of Enrollment Israel | 23 participants | 46 participants | 23 participants |
| Region of Enrollment North America | 212 participants | 452 participants | 240 participants |
| Region of Enrollment Russia | 23 participants | 48 participants | 25 participants |
| Sex: Female, Male Female | 360 Participants | 756 Participants | 396 Participants |
| Sex: Female, Male Male | 351 Participants | 720 Participants | 369 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 800 | 0 / 801 |
| other Total, other adverse events | 424 / 800 | 223 / 801 |
| serious Total, serious adverse events | 21 / 800 | 9 / 801 |
Outcome results
Primary
Total Combined Score
Average Total Combined Score (TCS), calculated for each patient as the average of the non-missing daily TCSs during the primary evaluation period. The daily TCS (scale 0-15) was the sum of the patient's daily Rhinitis Total Symptom Score (RTSS, scale 0-12) and daily Rescue Medication Score (RMS, scale 0-3). Lower is better.
Time frame: 12 months
Population: The FAS included all randomized patients (pts) who received at least one dose of the IP of treatment period and had at least one primary efficacy evaluation during the overall treatment period: 1,476 pts. Among these pts, only those with efficacy evaluation during the primary evaluation period were included in the primary analysis: 1,262 pts.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| 300 IR | Total Combined Score | 3.62 Units on a scale |
| Placebo | Total Combined Score | 4.35 Units on a scale |
p-value: <0.0001ANCOVA
Secondary
Average Rescue Medication Score (RMS)
Average RMS during the primary evaluation period. Rescue Medication Score (RMS) ; range 0-3, lower is better.
Time frame: 12 months
Population: The FAS included all randomized patients (pts) who received at least one dose of the IP of treatment period and had at least one primary efficacy evaluation during the overall treatment period: 1,476 pts. Among these pts, only those with efficacy evaluation during the primary evaluation period were included in the secondary analysis: 1,262 pts.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| 300 IR | Average Rescue Medication Score (RMS) | 0.21 Units on a scale |
| Placebo | Average Rescue Medication Score (RMS) | 0.30 Units on a scale |
Secondary
Average Rhinitis Total Symptom Score (RTSS)
Average RTSS during the primary evaluation period. The daily Total Symptom Scores (RTSS) was the sum of the 4 rhinitis symptom scores: sneezing, rhinorrhoea, nasal pruritus and nasal congestion, each graded on a 4-point scale (0-3; 0: absent, 1: mild, 2: moderate, 3: severe). It ranges from 0 to 12. Lower is better.
Time frame: 12 months
Population: The FAS included all randomized patients (pts) who received at least one dose of the IP of treatment period and had at least one primary efficacy evaluation during the overall treatment period: 1,476 pts. Among these pts, only those with efficacy evaluation during the primary evaluation period were included in the secondary analysis: 1,262 pts.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| 300 IR | Average Rhinitis Total Symptom Score (RTSS) | 3.16 Units on a scale |
| Placebo | Average Rhinitis Total Symptom Score (RTSS) | 3.79 Units on a scale |