Allergic Rhinitis, Conjunctivitis
Conditions
Keywords
Birch Allergy
Brief summary
The primary objective is to assess the reduction of allergic symptoms as measured by combined symptom and medication score (CSMS) during birch pollen season after a single dose of REGN5713-5714-5715 versus placebo.
Interventions
Sponsors
Regeneron Pharmaceuticals
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 No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria 1. Documented or participant-reported history of birch pollen-triggered allergic rhinitis symptoms, with or without conjunctivitis, for at least 2 years 2. Positive Skin prick test (SPT) with birch pollen extract in the screening period, as defined in the protocol 3. Positive Allergen-specific IgE (sIgE) tests for birch pollen and Bet v 1 in the screening period, as defined in the protocol 4. Willing and able to comply with clinic visits and study-related procedures Key
Exclusion criteria
1. Participation in a prior REGN5713-5714-5715 clinical trial 2. Recurrent or chronic rhinitis or sinusitis not associated with birch pollen season, or due to daily contact with other allergens causing symptoms that are expected to coincide with birch pollen season, as assessed by the investigator 3. Participants who anticipate major changes in allergen exposure in their home or work environments that are expected to coincide with the study assessments as assessed by the investigator 4. Persistent chronic or recurring acute infection requiring treatment with antibiotics, antivirals, or antifungals, or any untreated respiratory infections (at the discretion of the investigator) within 4 weeks prior to screening visit. Participants may be re-evaluated for eligibility after symptoms resolve 5. Documentation of active SARS-CoV-2 infection, as defined in the protocol 6. A clinical history of asthma with 2 or more asthma exacerbations requiring hospitalizations or systemic corticosteroids in the previous year 7. History of birch allergy immunotherapy as defined in the protocol 8. Use of anti-IgE or other biological therapy in treatment of asthma or allergy within 6 months prior to screening NOTE: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Combined Symptom and Medication Score (CSMS) in Participants Who Receive a Single Dose of REGN5713-5714-5715 Versus Placebo | Until the end of Birch Pollen Season, up to Week 16 | The average CSMS will be calculated based on daily symptom score and daily medication score recorded over the duration of the birch pollen season (BPS). CSMS is calculated by adding the Daily Medication Score (DMS) and Total Symptom Score (TSS) together, with scores ranging between 0 (none) and 38 (severe). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total Nasal Symptom Score (TNSS), Averaged Over the Duration of the Birch Pollen Season, in Participants Who Receive a Single Dose of REGN5713-5714-5715 Versus Placebo | Until the end of Birch Pollen Season, up to Week 16 | Total nasal symptom score (TNSS) is from 0 to 12 and is based on assessment of 4 nasal symptoms graded on a Likert scale ranging from 0 (none) to 3 (severe) for congestion, itching, and rhinorrhea, and from 0 (none) to 3 (5 or more sneezes) for sneezing. |
| Total Ocular Symptom Score (TOSS), Averaged Over the Duration of the Birch Pollen Season, in Participants Who Receive a Single Dose of REGN5713-5714-5715 Versus Placebo | Until the end of Birch Pollen Season, up to Week 16 | Total ocular symptom score is 0 to 6 and is based on itching/redness/gritty feeling and tearing/watering; each of the 2 symptoms is graded 0 (absent), 1 (mild), 2 (moderate), and 3 (severe) |
| Daily Medication Score (DMS), Averaged Over the Duration of the Birch Pollen Season, in Participants Who Receive a Single Dose of REGN5713-5714-5715 Versus Placebo | Until the end of Birch Pollen Season, up to Week 16 | The Daily Medication Score (DMS) is calculated by adding points for each pre-specified medication taken as follows: desloratadine 5 mg 6 points/dose; maximum daily score 6 points, olopatadine 1 mg/mL each drop 1.5 points/drop; maximum daily score 6 points, mometasone furoate 50 ug/dose 2.0 points/spray; maximum daily score 8 points). The scale is 0 (minimum) to 20 (maximum) |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Throughout the Study | Up to Day 127 | Number of participants with any Treatment Emergent Adverse Events (TEAEs) from participating in study |
| Number of Participants With Serious TEAEs Throughout the Study | Up to Day 127 | Number of participants with any Serious Treatment Emergent Adverse Events (TEAEs) from participating in study |
| Change From Baseline to the End of Study in Birch SPT Mean Wheal Diameter in Participants Who Receive a Single Dose of REGN5713-5714-5715 Versus Placebo | Baseline through Day 127 | Number of participants who showed change from baseline to the end of the study in Birch Skin Prick Test (SPT) Mean Wheal Diameter, in participants who received REGN5713-5714-5715 compared to placebo |
| Percent Change From Baseline to the End of Study in Birch SPT Mean Wheal Diameter in Participants Who Receive a Single Dose of REGN5713-5714-5715 Versus Placebo | Baseline through Day 127 | — |
| Total Symptom Score (TSS), Averaged Over the Duration of the Birch Pollen Season, in Participants Who Receive a Single Dose of REGN5713-5714-5715 Versus Placebo | Until the end of Birch Pollen Season, up to Week 16 | TSS is a combined score of TOSS and TNSS. TNSS and TOSS are scored as in part 1 each for a combined TSS of 0 (none) to 18 (severe) |
| Serum Concentration of REGN5714 Over the Study Duration | Up to Day 127 | — |
| Serum Concentration of REGN5715 Over the Study Duration | Up to Day 127 | — |
| Percentage of Participants With Treatment Emergent Anti-drug Antibodies to REGN5713 Throughout the Study | Up to Day 127 | Percentage of participants who developed antibodies to intervention provided during study |
| Percentage of Participants With Treatment Emergent Anti-drug Antibodies to REGN5714 Throughout the Study | Up to Day 127 | Percentage of participants who developed antibodies to intervention provided during study |
| Percentage of Participants With Treatment Emergent Anti-drug Antibodies to REGN5715 Throughout the Study | Up to Day 127 | Percentage of participants who developed antibodies to intervention provided during study |
| Number of Well Days | Until the end of Birch Pollen Season, up to Week 16 | Well Days are defined as days when rescue medication is not utilized and the Total symptom score (TSS) is ≤2/18 |
| Serum Concentration of REGN5713 Over the Study Duration | Day 0, Day 56, Day 112 | — |
Countries
Belgium, Canada, Denmark, Germany, United States
Participant flow
Pre-assignment details
589 participants screened, 353 randomized and from these 349 treated. 4 participants were randomized but not treated. Reasons not randomized: 235 did not meet I/E criteria, 1 withdrew consent.
Participants by arm
| Arm | Count |
|---|---|
| REGN5713-5714-5715 REGN5713-5714-5715 administered subcutaneously | 176 |
| Placebo Only Placebo matching REGN5713-5714-5715 administered subcutaneously | 177 |
| Total | 353 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Lost to Follow-up | 2 | 2 |
| Overall Study | Protocol Violation | 1 | 1 |
| Overall Study | Withdrawal by Subject | 6 | 2 |
Baseline characteristics
| Characteristic | Placebo Only | Total | REGN5713-5714-5715 |
|---|---|---|---|
| Age, Continuous | 42.1 years STANDARD_DEVIATION 14.36 | 40.9 years STANDARD_DEVIATION 14.29 | 39.6 years STANDARD_DEVIATION 14.15 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 4 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 174 Participants | 346 Participants | 172 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 10 Participants | 13 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 3 Participants | 1 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 | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 9 Participants | 6 Participants |
| Race (NIH/OMB) White | 161 Participants | 326 Participants | 165 Participants |
| Sex: Female, Male Female | 102 Participants | 204 Participants | 102 Participants |
| Sex: Female, Male Male | 75 Participants | 149 Participants | 74 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 176 | 0 / 173 |
| other Total, other adverse events | 43 / 176 | 32 / 173 |
| serious Total, serious adverse events | 0 / 176 | 3 / 173 |
Outcome results
Primary
Combined Symptom and Medication Score (CSMS) in Participants Who Receive a Single Dose of REGN5713-5714-5715 Versus Placebo
The average CSMS will be calculated based on daily symptom score and daily medication score recorded over the duration of the birch pollen season (BPS). CSMS is calculated by adding the Daily Medication Score (DMS) and Total Symptom Score (TSS) together, with scores ranging between 0 (none) and 38 (severe).
Time frame: Until the end of Birch Pollen Season, up to Week 16
Population: All randomized participants with at least 1 e-diary entry with symptoms or medication score recorded during the birch pollen season.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| REGN5713-5714-5715 | Combined Symptom and Medication Score (CSMS) in Participants Who Receive a Single Dose of REGN5713-5714-5715 Versus Placebo | 7.503 Scores on a Scale | Standard Error 0.6545 |
| Placebo Only | Combined Symptom and Medication Score (CSMS) in Participants Who Receive a Single Dose of REGN5713-5714-5715 Versus Placebo | 8.498 Scores on a Scale | Standard Error 0.6534 |
p-value: 0.049795% CI: [-1.9886, -0.0011]LS Mean Difference
Secondary
Change From Baseline to the End of Study in Birch SPT Mean Wheal Diameter in Participants Who Receive a Single Dose of REGN5713-5714-5715 Versus Placebo
Number of participants who showed change from baseline to the end of the study in Birch Skin Prick Test (SPT) Mean Wheal Diameter, in participants who received REGN5713-5714-5715 compared to placebo
Time frame: Baseline through Day 127
Population: All randomized participants with at least 1 e-diary entry with symptoms or medication score recorded during the birch pollen season
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| REGN5713-5714-5715 | Change From Baseline to the End of Study in Birch SPT Mean Wheal Diameter in Participants Who Receive a Single Dose of REGN5713-5714-5715 Versus Placebo | -3.139 millimeters | Standard Error 0.5086 |
| Placebo Only | Change From Baseline to the End of Study in Birch SPT Mean Wheal Diameter in Participants Who Receive a Single Dose of REGN5713-5714-5715 Versus Placebo | 0.553 millimeters | Standard Error 0.5067 |
Secondary
Daily Medication Score (DMS), Averaged Over the Duration of the Birch Pollen Season, in Participants Who Receive a Single Dose of REGN5713-5714-5715 Versus Placebo
The Daily Medication Score (DMS) is calculated by adding points for each pre-specified medication taken as follows: desloratadine 5 mg 6 points/dose; maximum daily score 6 points, olopatadine 1 mg/mL each drop 1.5 points/drop; maximum daily score 6 points, mometasone furoate 50 ug/dose 2.0 points/spray; maximum daily score 8 points). The scale is 0 (minimum) to 20 (maximum)
Time frame: Until the end of Birch Pollen Season, up to Week 16
Population: All randomized participants with at least 1 e-diary entry with symptoms or medication score recorded during the birch pollen season
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| REGN5713-5714-5715 | Daily Medication Score (DMS), Averaged Over the Duration of the Birch Pollen Season, in Participants Who Receive a Single Dose of REGN5713-5714-5715 Versus Placebo | 2.316 Score on a Scale | Standard Error 0.3993 |
| Placebo Only | Daily Medication Score (DMS), Averaged Over the Duration of the Birch Pollen Season, in Participants Who Receive a Single Dose of REGN5713-5714-5715 Versus Placebo | 2.882 Score on a Scale | Standard Error 0.3986 |
Secondary
Number of Participants With Serious TEAEs Throughout the Study
Number of participants with any Serious Treatment Emergent Adverse Events (TEAEs) from participating in study
Time frame: Up to Day 127
Population: All participants in Safety Analysis Set (SAF) who received study drug and were recorded, if symptoms were displayed or not
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| REGN5713-5714-5715 | Number of Participants With Serious TEAEs Throughout the Study | 3 Count of Participants |
| Placebo Only | Number of Participants With Serious TEAEs Throughout the Study | 0 Count of Participants |
Secondary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Throughout the Study
Number of participants with any Treatment Emergent Adverse Events (TEAEs) from participating in study
Time frame: Up to Day 127
Population: All participants in Safety Analysis Set (SAF) who received study drug and were recorded, if symptoms were displayed or not
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| REGN5713-5714-5715 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Throughout the Study | 92 Count of Participants |
| Placebo Only | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Throughout the Study | 85 Count of Participants |
Secondary
Number of Well Days
Well Days are defined as days when rescue medication is not utilized and the Total symptom score (TSS) is ≤2/18
Time frame: Until the end of Birch Pollen Season, up to Week 16
Population: All randomized participants with at least 1 e-diary entry with symptoms or medication score recorded during the birch pollen season
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| REGN5713-5714-5715 | Number of Well Days | 8.3 Days | Standard Error 1.42 |
| Placebo Only | Number of Well Days | 8.6 Days | Standard Error 1.42 |
Secondary
Percentage of Participants With Treatment Emergent Anti-drug Antibodies to REGN5713 Throughout the Study
Percentage of participants who developed antibodies to intervention provided during study
Time frame: Up to Day 127
Population: All randomized and treated participants who recorded and contributed to each timepoint (+/- 14 days)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| REGN5713-5714-5715 | Percentage of Participants With Treatment Emergent Anti-drug Antibodies to REGN5713 Throughout the Study | 0 Percentage of Participants |
| Placebo Only | Percentage of Participants With Treatment Emergent Anti-drug Antibodies to REGN5713 Throughout the Study | 0 Percentage of Participants |
Secondary
Percentage of Participants With Treatment Emergent Anti-drug Antibodies to REGN5714 Throughout the Study
Percentage of participants who developed antibodies to intervention provided during study
Time frame: Up to Day 127
Population: All randomized and treated participants who recorded and contributed to each timepoint (+/- 14 days)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| REGN5713-5714-5715 | Percentage of Participants With Treatment Emergent Anti-drug Antibodies to REGN5714 Throughout the Study | 0 Percentage of Participants |
| Placebo Only | Percentage of Participants With Treatment Emergent Anti-drug Antibodies to REGN5714 Throughout the Study | 0 Percentage of Participants |
Secondary
Percentage of Participants With Treatment Emergent Anti-drug Antibodies to REGN5715 Throughout the Study
Percentage of participants who developed antibodies to intervention provided during study
Time frame: Up to Day 127
Population: All randomized and treated participants who recorded and contributed to each timepoint (+/- 14 days)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| REGN5713-5714-5715 | Percentage of Participants With Treatment Emergent Anti-drug Antibodies to REGN5715 Throughout the Study | 0 Percentage of Participants |
| Placebo Only | Percentage of Participants With Treatment Emergent Anti-drug Antibodies to REGN5715 Throughout the Study | 0 Percentage of Participants |
Secondary
Percent Change From Baseline to the End of Study in Birch SPT Mean Wheal Diameter in Participants Who Receive a Single Dose of REGN5713-5714-5715 Versus Placebo
Time frame: Baseline through Day 127
Population: All randomized participants with at least 1 e-diary entry with symptoms or medication score recorded during the birch pollen season
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| REGN5713-5714-5715 | Percent Change From Baseline to the End of Study in Birch SPT Mean Wheal Diameter in Participants Who Receive a Single Dose of REGN5713-5714-5715 Versus Placebo | -26.38 Percentage | Standard Error 5.179 |
| Placebo Only | Percent Change From Baseline to the End of Study in Birch SPT Mean Wheal Diameter in Participants Who Receive a Single Dose of REGN5713-5714-5715 Versus Placebo | 8.17 Percentage | Standard Error 5.16 |
Secondary
Serum Concentration of REGN5713 Over the Study Duration
Time frame: Day 0, Day 56, Day 112
Population: All randomized and treated participants who recorded and contributed to each timepoint (+/- 14 days)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| REGN5713-5714-5715 | Serum Concentration of REGN5713 Over the Study Duration | Day 0 | 0 mg/L | Standard Deviation 0 |
| REGN5713-5714-5715 | Serum Concentration of REGN5713 Over the Study Duration | Day 56 | 10.0 mg/L | Standard Deviation 3.97 |
| REGN5713-5714-5715 | Serum Concentration of REGN5713 Over the Study Duration | Day 112 | 2.53 mg/L | Standard Deviation 1.57 |
Secondary
Serum Concentration of REGN5714 Over the Study Duration
Time frame: Up to Day 127
Population: All randomized and treated participants who recorded and contributed to each timepoint (+/- 14 days)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| REGN5713-5714-5715 | Serum Concentration of REGN5714 Over the Study Duration | Day 0 | 0 mg/L | Standard Deviation 0 |
| REGN5713-5714-5715 | Serum Concentration of REGN5714 Over the Study Duration | Day 56 | 14.7 mg/L | Standard Deviation 4.68 |
| REGN5713-5714-5715 | Serum Concentration of REGN5714 Over the Study Duration | Day 112 | 4.82 mg/L | Standard Deviation 2.16 |
Secondary
Serum Concentration of REGN5715 Over the Study Duration
Time frame: Up to Day 127
Population: All randomized and treated participants who recorded and contributed to each timepoint (+/- 14 days)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| REGN5713-5714-5715 | Serum Concentration of REGN5715 Over the Study Duration | Day 0 | 0 mg/L | Standard Deviation 0 |
| REGN5713-5714-5715 | Serum Concentration of REGN5715 Over the Study Duration | Day 56 | 16.6 mg/L | Standard Deviation 5.34 |
| REGN5713-5714-5715 | Serum Concentration of REGN5715 Over the Study Duration | Day 112 | 5.34 mg/L | Standard Deviation 2.35 |
Secondary
Total Nasal Symptom Score (TNSS), Averaged Over the Duration of the Birch Pollen Season, in Participants Who Receive a Single Dose of REGN5713-5714-5715 Versus Placebo
Total nasal symptom score (TNSS) is from 0 to 12 and is based on assessment of 4 nasal symptoms graded on a Likert scale ranging from 0 (none) to 3 (severe) for congestion, itching, and rhinorrhea, and from 0 (none) to 3 (5 or more sneezes) for sneezing.
Time frame: Until the end of Birch Pollen Season, up to Week 16
Population: All randomized participants with at least 1 e-diary entry with symptoms or medication score recorded during the birch pollen season
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| REGN5713-5714-5715 | Total Nasal Symptom Score (TNSS), Averaged Over the Duration of the Birch Pollen Season, in Participants Who Receive a Single Dose of REGN5713-5714-5715 Versus Placebo | 3.76 Score on a scale | Standard Error 0.278 |
| Placebo Only | Total Nasal Symptom Score (TNSS), Averaged Over the Duration of the Birch Pollen Season, in Participants Who Receive a Single Dose of REGN5713-5714-5715 Versus Placebo | 4.00 Score on a scale | Standard Error 0.277 |
Secondary
Total Ocular Symptom Score (TOSS), Averaged Over the Duration of the Birch Pollen Season, in Participants Who Receive a Single Dose of REGN5713-5714-5715 Versus Placebo
Total ocular symptom score is 0 to 6 and is based on itching/redness/gritty feeling and tearing/watering; each of the 2 symptoms is graded 0 (absent), 1 (mild), 2 (moderate), and 3 (severe)
Time frame: Until the end of Birch Pollen Season, up to Week 16
Population: All randomized participants with at least 1 e-diary entry with symptoms or medication score recorded during the birch pollen season
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| REGN5713-5714-5715 | Total Ocular Symptom Score (TOSS), Averaged Over the Duration of the Birch Pollen Season, in Participants Who Receive a Single Dose of REGN5713-5714-5715 Versus Placebo | 1.43 Score on a scale | Standard Error 0.15 |
| Placebo Only | Total Ocular Symptom Score (TOSS), Averaged Over the Duration of the Birch Pollen Season, in Participants Who Receive a Single Dose of REGN5713-5714-5715 Versus Placebo | 1.62 Score on a scale | Standard Error 0.15 |
Secondary
Total Symptom Score (TSS), Averaged Over the Duration of the Birch Pollen Season, in Participants Who Receive a Single Dose of REGN5713-5714-5715 Versus Placebo
TSS is a combined score of TOSS and TNSS. TNSS and TOSS are scored as in part 1 each for a combined TSS of 0 (none) to 18 (severe)
Time frame: Until the end of Birch Pollen Season, up to Week 16
Population: All randomized participants with at least 1 e-diary entry with symptoms or medication score recorded during the birch pollen season
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| REGN5713-5714-5715 | Total Symptom Score (TSS), Averaged Over the Duration of the Birch Pollen Season, in Participants Who Receive a Single Dose of REGN5713-5714-5715 Versus Placebo | 5.19 Scores on a Scale | Standard Error 0.397 |
| Placebo Only | Total Symptom Score (TSS), Averaged Over the Duration of the Birch Pollen Season, in Participants Who Receive a Single Dose of REGN5713-5714-5715 Versus Placebo | 5.62 Scores on a Scale | Standard Error 0.396 |