Cat Allergy, Mild Asthma
Conditions
Brief summary
The primary objective is to evaluate the prophylactic efficacy of REGN1908-1909 (anti-Fel d 1) administered as a single dose on day 1 in cat-allergic asthmatic patients not living with a cat in the prevention of a Controlled Cat Allergen Challenge-induced early asthmatic response (EAR) assessed by measures of lung function (FEV1) compared to placebo-treated patients. Secondary Efficacy Objectives: * To evaluate the prophylactic efficacy of REGN1908-1909 administered as a single dose on day 1 in cat-allergic asthmatic patients not living with a cat, in the prevention of a Controlled Cat Allergen Challenge-induced: Allergic rhinitis and Ocular symptoms * To evaluate the prophylactic efficacy of REGN1908-1909 administered as a single dose on day 1 in cat-allergic asthmatic patients not living with a cat to increase the exposure to cat allergen, measured as a product of minute ventilation and time, required to induce EAR in a Controlled Cat Allergen Challenge as compared to placebo patients Secondary Safety Objective: * To evaluate the safety and tolerability of REGN1908-1909 vs. placebo in patients with cat allergen-triggered asthma
Interventions
DRUGREGN1908-1909
Single subcutaneous (SC) dose of REGN1908 and REGN1909
DRUGPlacebo
Single subcutaneous (SC) dose of matching placebo
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 65 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Documented or patient reported history (for at least 2 years) of symptomatic cat allergen-triggered asthma with rhinitis with or without conjunctivitis * No cat exposure at home for the past year and must continue having no exposure at home during the study; cat exposure outside of the home shall be avoided for at least one week prior to any Cat Allergen Challenge and during the defined follow-up period * Less than 10 pack-years of smoking history Key
Exclusion criteria
* Positive human immunodeficiency virus (HIV) test * Positive hepatitis test (HBsAg and hepatitis C antibody) * History of significant multiple and/or severe allergies (including latex gloves) or has had an anaphylactic reaction or significant intolerability to prescription or nonprescription drugs or food * Participation in a prior REGN1908-1909 clinical trial * History of severe anaphylactic or severe asthmatic reactions to cat exposure * Active lung disease other than asthma * Treatment with an investigational drug within 2 months or within 5 half-lives (if known), whichever is longer, prior to screening * Persistent chronic or recurring acute infection requiring treatment with antibiotics, antivirals, or antifungals, or any untreated respiratory infections within 4 weeks prior to screening * History of life-threatening asthma, defined as an asthma episode that required intubation and/or was associated with hypercapnia, respiratory arrest, and/or hypoxic seizures * Treatment of asthma requiring systemic (oral or parenteral) corticosteroid treatment more than twice within 12 months or once within 3 months prior to screening or has been hospitalized or has attended the ER/Urgent Care facility for asthma more than twice in prior 12 months before screening. * History of hypersensitivity to corticosteroids or antihistamines, or drug treatment excipient Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Early Asthmatic Response (EAR) Upon Controlled Cat Allergen Challenge in an Environmental Exposure Unit (EEU) on Day 8 | Day 8 | Time to EAR was defined as the time to a ≥20% reduction in FEV1 or when the participant voluntarily departed the EEU due to clinically significant allergic and/or asthmatic symptoms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to EAR Upon Controlled Cat Allergen Challenge in an EEU on Days 29, 57, and 85 | Days 29, 57 and 85 | Time to EAR was defined as the time to a ≥20% reduction in FEV1 or when the participant voluntarily departed the EEU due to clinically significant allergic and/or asthmatic symptoms |
| Percent Change in Normalized Area Under the Curve (AUC) of Forced Expiratory Volume in 1 Second (FEV1) Induced by a Controlled Cat Allergen Challenge Over Exposure Interval From Baseline to Controlled Cat Allergen Challenge on Days 8, 29, 57, and 85 | Days 8, 29, 57, and 85 | The AUC was analyzed by mixed-effect model repeated measures (MMRM) with the treatment, time, treatment-by-time interaction, and day of challenge as factors and baseline FEV1 AUC as a continuous covariate. |
| Change in Normalized Area Under the Curve (AUC) of Forced Expiratory Volume in 1 Second (FEV1) Induced by a Controlled Cat Allergen Challenge Over Exposure Interval From Baseline to Controlled Cat Allergen Challenge on Days 8, 29, 57, and 85 | Days 8, 29, 57, and 85 | The AUC was analyzed by mixed-effect model repeated measures (MMRM) with the treatment, time, treatment-by-time interaction, and day of challenge as factors and baseline FEV1 AUC as a continuous covariate. |
| Change From Baseline in the Normalized AUC of Patient-Assessed Nasal Symptoms Induced by a Controlled Cat Allergen Challenge Over the Exposure Interval to the Controlled Cat Allergen Challenge on Days 8, 29, 57, and 85 | Days 8, 29, 57 and 85 | Individual nasal symptoms, including rhinorrhea, nasal congestion, nasal itching, and sneezing were evaluated on a 4-point Likert scale (0, none; 1, mild; 2, moderate; and 3, severe) and combined to give the Total Nasal Symptom Score (TNSS) with a maximum score of 12. Scale range is 0-12. The higher the score, the more severe the symptoms. |
| Change From Baseline in the Normalized AUC in Patient-Assessed Ocular Symptoms Induced by a Controlled Cat Allergen Challenge Over the Exposure Interval to the Controlled Cat Allergen Challenge on Days 8, 29, 57, and 85 | Days 8, 29, 57 and 85 | Individual ocular symptoms for itching/burning, redness, swelling/puffiness, and tearing/watery eyes were evaluated on a 4-point Likert scale (0, none; 1, mild; 2, moderate; and 3, severe) and combined to give the TOSS, with a maximum score of 12. Score range is 0-12. The higher the score, the more severe the symptoms. |
| Mean Change From Baseline in Cat Allergen Quantity as Experienced by Participants During Exposure on Days 8, 29, 57, and 85 | Days 8, 29, 57 and 85 | Cat Allergen Exposure Tolerated in ng = Minute Ventilation (L/min) x Allergen Concentration (ng/m3) x Time in EEU (minutes), where 1 L/min = 0.001 m3/min. The change in cat allergen quantity (tolerated exposure) from the baseline Cat Allergen Challenge, will be analyzed using a similar MMRM model with treatment, visit and treatment by-visit interaction as factors and the cat allergen quantity tolerated in the baseline Controlled Cat Allergen Challenge as a covariate. |
| Percent Change in Cat Allergen Quantity as Experienced by Participants During Exposure on Days 8, 29, 57, and 85 | Days 8, 29, 57 and 85 | Cat Allergen Exposure Tolerated in ng = Minute Ventilation (L/min) x Allergen Concentration (ng/m3) x Time in EEU (minutes), where 1 L/min = 0.001 m3/min. The change in cat allergen quantity (tolerated exposure) from the baseline Cat Allergen Challenge, will be analyzed using a similar MMRM model with treatment, visit and treatment by-visit interaction as factors and the cat allergen quantity tolerated in the baseline Controlled Cat Allergen Challenge as a covariate. |
| Number of Non-Serious and Serious Treatment-Emergent Adverse Events (TEAEs) Through End of Study | Baseline to 16 weeks | Adverse events and serious adverse events were collected from the time of informed consent signature and then at each visit until the end of the study with the exception of symptoms that occurred in response to the EEU within 24 hours following the EEU. |
Countries
France
Participant flow
Recruitment details
A total of 130 participants were screened for study eligibility. Screen failures were mostly attributed to eligibility criteria not being met. The study was conducted at one site in France.
Pre-assignment details
A total of 56 participants were randomized in a 1:1 ratio to receive a single dose of either 600 milligrams (mg) of REGN1908-1909 or matching placebo.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received a single dose of matching placebo | 27 |
| REGN1908-1909 600 mg Participants received a single 600 mg dose of REGN1908-1909 | 29 |
| Total | 56 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Pregnancy | 0 | 1 |
| Overall Study | Withdrawal of consent | 1 | 0 |
Baseline characteristics
| Characteristic | REGN1908-1909 600 mg | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 28.4 Years STANDARD_DEVIATION 7.1 | 29.3 Years STANDARD_DEVIATION 8 | 30.2 Years STANDARD_DEVIATION 8.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 2 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 28 Participants | 54 Participants | 26 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 3 Participants | 3 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 27 Participants | 51 Participants | 24 Participants |
| Sex: Female, Male Female | 18 Participants | 35 Participants | 17 Participants |
| Sex: Female, Male Male | 11 Participants | 21 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 27 | 0 / 29 |
| other Total, other adverse events | 19 / 27 | 22 / 29 |
| serious Total, serious adverse events | 0 / 27 | 0 / 29 |
Outcome results
Primary
Time to Early Asthmatic Response (EAR) Upon Controlled Cat Allergen Challenge in an Environmental Exposure Unit (EEU) on Day 8
Time to EAR was defined as the time to a ≥20% reduction in FEV1 or when the participant voluntarily departed the EEU due to clinically significant allergic and/or asthmatic symptoms.
Time frame: Day 8
Population: Full analysis set: included all randomized participants who received any investigational product and had completed the Day 8 Cat Allergen Challenge.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to Early Asthmatic Response (EAR) Upon Controlled Cat Allergen Challenge in an Environmental Exposure Unit (EEU) on Day 8 | 51 Minutes |
| REGN1908-1909 600 mg | Time to Early Asthmatic Response (EAR) Upon Controlled Cat Allergen Challenge in an Environmental Exposure Unit (EEU) on Day 8 | NA Minutes |
p-value: =0.008395% CI: [0.17, 0.77]Cox Proportional Hazard
Secondary
Change From Baseline in the Normalized AUC in Patient-Assessed Ocular Symptoms Induced by a Controlled Cat Allergen Challenge Over the Exposure Interval to the Controlled Cat Allergen Challenge on Days 8, 29, 57, and 85
Individual ocular symptoms for itching/burning, redness, swelling/puffiness, and tearing/watery eyes were evaluated on a 4-point Likert scale (0, none; 1, mild; 2, moderate; and 3, severe) and combined to give the TOSS, with a maximum score of 12. Score range is 0-12. The higher the score, the more severe the symptoms.
Time frame: Days 8, 29, 57 and 85
Population: Full analysis set; Here 'n' = number of evaluable participants analyzed at each time point. For each participant at each controlled cat allergen challenge, AUC was calculated over the time period of 0 to 2 hours, with last observation carried forward used to impute values out to 2 hours if participants remained in EEU for less than 2 hours. AUCs were calculated using trapezoidal rule and were normalized by dividing by the length of time (2 hours).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in the Normalized AUC in Patient-Assessed Ocular Symptoms Induced by a Controlled Cat Allergen Challenge Over the Exposure Interval to the Controlled Cat Allergen Challenge on Days 8, 29, 57, and 85 | Day 8 | -0.37 Scores on a scale | Standard Error 0.17 |
| Placebo | Change From Baseline in the Normalized AUC in Patient-Assessed Ocular Symptoms Induced by a Controlled Cat Allergen Challenge Over the Exposure Interval to the Controlled Cat Allergen Challenge on Days 8, 29, 57, and 85 | Day 29 | -0.43 Scores on a scale | Standard Error 0.15 |
| Placebo | Change From Baseline in the Normalized AUC in Patient-Assessed Ocular Symptoms Induced by a Controlled Cat Allergen Challenge Over the Exposure Interval to the Controlled Cat Allergen Challenge on Days 8, 29, 57, and 85 | Day 57 | -0.40 Scores on a scale | Standard Error 0.15 |
| Placebo | Change From Baseline in the Normalized AUC in Patient-Assessed Ocular Symptoms Induced by a Controlled Cat Allergen Challenge Over the Exposure Interval to the Controlled Cat Allergen Challenge on Days 8, 29, 57, and 85 | Day 85 | -0.36 Scores on a scale | Standard Error 0.11 |
| REGN1908-1909 600 mg | Change From Baseline in the Normalized AUC in Patient-Assessed Ocular Symptoms Induced by a Controlled Cat Allergen Challenge Over the Exposure Interval to the Controlled Cat Allergen Challenge on Days 8, 29, 57, and 85 | Day 85 | -0.51 Scores on a scale | Standard Error 0.1 |
| REGN1908-1909 600 mg | Change From Baseline in the Normalized AUC in Patient-Assessed Ocular Symptoms Induced by a Controlled Cat Allergen Challenge Over the Exposure Interval to the Controlled Cat Allergen Challenge on Days 8, 29, 57, and 85 | Day 8 | -0.23 Scores on a scale | Standard Error 0.17 |
| REGN1908-1909 600 mg | Change From Baseline in the Normalized AUC in Patient-Assessed Ocular Symptoms Induced by a Controlled Cat Allergen Challenge Over the Exposure Interval to the Controlled Cat Allergen Challenge on Days 8, 29, 57, and 85 | Day 57 | -0.34 Scores on a scale | Standard Error 0.15 |
| REGN1908-1909 600 mg | Change From Baseline in the Normalized AUC in Patient-Assessed Ocular Symptoms Induced by a Controlled Cat Allergen Challenge Over the Exposure Interval to the Controlled Cat Allergen Challenge on Days 8, 29, 57, and 85 | Day 29 | -0.43 Scores on a scale | Standard Error 0.14 |
Comparison: Day 8p-value: =0.57295% CI: [-0.35, 0.63]MMRM
Comparison: Day 29p-value: =0.99795% CI: [-0.41, 0.41]MMRM
Comparison: Day 57p-value: =0.75695% CI: [-0.36, 0.49]MMRM
Comparison: Day 85p-value: =0.33395% CI: [-0.46, 0.16]MMRM
Secondary
Change From Baseline in the Normalized AUC of Patient-Assessed Nasal Symptoms Induced by a Controlled Cat Allergen Challenge Over the Exposure Interval to the Controlled Cat Allergen Challenge on Days 8, 29, 57, and 85
Individual nasal symptoms, including rhinorrhea, nasal congestion, nasal itching, and sneezing were evaluated on a 4-point Likert scale (0, none; 1, mild; 2, moderate; and 3, severe) and combined to give the Total Nasal Symptom Score (TNSS) with a maximum score of 12. Scale range is 0-12. The higher the score, the more severe the symptoms.
Time frame: Days 8, 29, 57 and 85
Population: Full analysis set; Here 'n' = number of evaluable participants analyzed at each time point. For each participant at each controlled cat allergen challenge, AUC was calculated over the time period of 0 to 2 hours, with last observation carried forward used to impute values out to 2 hours if participants remained in EEU for less than 2 hours. AUCs were calculated using trapezoidal rule and were normalized by dividing by the length of time (2 hours).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in the Normalized AUC of Patient-Assessed Nasal Symptoms Induced by a Controlled Cat Allergen Challenge Over the Exposure Interval to the Controlled Cat Allergen Challenge on Days 8, 29, 57, and 85 | Day 8 | -0.71 Scores on a scale | Standard Error 0.38 |
| Placebo | Change From Baseline in the Normalized AUC of Patient-Assessed Nasal Symptoms Induced by a Controlled Cat Allergen Challenge Over the Exposure Interval to the Controlled Cat Allergen Challenge on Days 8, 29, 57, and 85 | Day 29 | -0.70 Scores on a scale | Standard Error 0.37 |
| Placebo | Change From Baseline in the Normalized AUC of Patient-Assessed Nasal Symptoms Induced by a Controlled Cat Allergen Challenge Over the Exposure Interval to the Controlled Cat Allergen Challenge on Days 8, 29, 57, and 85 | Day 57 | -0.93 Scores on a scale | Standard Error 0.43 |
| Placebo | Change From Baseline in the Normalized AUC of Patient-Assessed Nasal Symptoms Induced by a Controlled Cat Allergen Challenge Over the Exposure Interval to the Controlled Cat Allergen Challenge on Days 8, 29, 57, and 85 | Day 85 | -0.49 Scores on a scale | Standard Error 0.43 |
| REGN1908-1909 600 mg | Change From Baseline in the Normalized AUC of Patient-Assessed Nasal Symptoms Induced by a Controlled Cat Allergen Challenge Over the Exposure Interval to the Controlled Cat Allergen Challenge on Days 8, 29, 57, and 85 | Day 85 | -1.37 Scores on a scale | Standard Error 0.41 |
| REGN1908-1909 600 mg | Change From Baseline in the Normalized AUC of Patient-Assessed Nasal Symptoms Induced by a Controlled Cat Allergen Challenge Over the Exposure Interval to the Controlled Cat Allergen Challenge on Days 8, 29, 57, and 85 | Day 8 | -0.49 Scores on a scale | Standard Error 0.38 |
| REGN1908-1909 600 mg | Change From Baseline in the Normalized AUC of Patient-Assessed Nasal Symptoms Induced by a Controlled Cat Allergen Challenge Over the Exposure Interval to the Controlled Cat Allergen Challenge on Days 8, 29, 57, and 85 | Day 57 | -0.83 Scores on a scale | Standard Error 0.43 |
| REGN1908-1909 600 mg | Change From Baseline in the Normalized AUC of Patient-Assessed Nasal Symptoms Induced by a Controlled Cat Allergen Challenge Over the Exposure Interval to the Controlled Cat Allergen Challenge on Days 8, 29, 57, and 85 | Day 29 | -1.39 Scores on a scale | Standard Error 0.34 |
Comparison: Day 8p-value: =0.67595% CI: [-0.85, 1.29]MMRM
Comparison: Day 29p-value: =0.18295% CI: [-1.7, 0.33]MMRM
Comparison: Day 57p-value: =0.86695% CI: [-1.12, 1.32]MMRM
Comparison: Day 85p-value: =0.14695% CI: [-2.08, 0.32]MMRM
Secondary
Change in Normalized Area Under the Curve (AUC) of Forced Expiratory Volume in 1 Second (FEV1) Induced by a Controlled Cat Allergen Challenge Over Exposure Interval From Baseline to Controlled Cat Allergen Challenge on Days 8, 29, 57, and 85
The AUC was analyzed by mixed-effect model repeated measures (MMRM) with the treatment, time, treatment-by-time interaction, and day of challenge as factors and baseline FEV1 AUC as a continuous covariate.
Time frame: Days 8, 29, 57, and 85
Population: Full analysis set; Here n = number of evaluable participants analyzed at each time point. For each participant at each controlled cat allergen challenge, AUC was calculated over the time period of 0 to 2 hours, with last observation carried forward used to impute values out to 2 hours if the patients remained in EEU for less than 2 hours. The AUCs were calculated using the trapezoidal rule and were normalized by dividing by the length of time (2 hours).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change in Normalized Area Under the Curve (AUC) of Forced Expiratory Volume in 1 Second (FEV1) Induced by a Controlled Cat Allergen Challenge Over Exposure Interval From Baseline to Controlled Cat Allergen Challenge on Days 8, 29, 57, and 85 | Day 8 | 0.01 Liters (L) | Standard Error 0.06 |
| Placebo | Change in Normalized Area Under the Curve (AUC) of Forced Expiratory Volume in 1 Second (FEV1) Induced by a Controlled Cat Allergen Challenge Over Exposure Interval From Baseline to Controlled Cat Allergen Challenge on Days 8, 29, 57, and 85 | Day 29 | -0.03 Liters (L) | Standard Error 0.08 |
| Placebo | Change in Normalized Area Under the Curve (AUC) of Forced Expiratory Volume in 1 Second (FEV1) Induced by a Controlled Cat Allergen Challenge Over Exposure Interval From Baseline to Controlled Cat Allergen Challenge on Days 8, 29, 57, and 85 | Day 57 | 0.00 Liters (L) | Standard Error 0.08 |
| Placebo | Change in Normalized Area Under the Curve (AUC) of Forced Expiratory Volume in 1 Second (FEV1) Induced by a Controlled Cat Allergen Challenge Over Exposure Interval From Baseline to Controlled Cat Allergen Challenge on Days 8, 29, 57, and 85 | Day 85 | -0.05 Liters (L) | Standard Error 0.08 |
| REGN1908-1909 600 mg | Change in Normalized Area Under the Curve (AUC) of Forced Expiratory Volume in 1 Second (FEV1) Induced by a Controlled Cat Allergen Challenge Over Exposure Interval From Baseline to Controlled Cat Allergen Challenge on Days 8, 29, 57, and 85 | Day 85 | 0.32 Liters (L) | Standard Error 0.08 |
| REGN1908-1909 600 mg | Change in Normalized Area Under the Curve (AUC) of Forced Expiratory Volume in 1 Second (FEV1) Induced by a Controlled Cat Allergen Challenge Over Exposure Interval From Baseline to Controlled Cat Allergen Challenge on Days 8, 29, 57, and 85 | Day 8 | 0.38 Liters (L) | Standard Error 0.06 |
| REGN1908-1909 600 mg | Change in Normalized Area Under the Curve (AUC) of Forced Expiratory Volume in 1 Second (FEV1) Induced by a Controlled Cat Allergen Challenge Over Exposure Interval From Baseline to Controlled Cat Allergen Challenge on Days 8, 29, 57, and 85 | Day 57 | 0.34 Liters (L) | Standard Error 0.07 |
| REGN1908-1909 600 mg | Change in Normalized Area Under the Curve (AUC) of Forced Expiratory Volume in 1 Second (FEV1) Induced by a Controlled Cat Allergen Challenge Over Exposure Interval From Baseline to Controlled Cat Allergen Challenge on Days 8, 29, 57, and 85 | Day 29 | 0.43 Liters (L) | Standard Error 0.08 |
Comparison: Day 8p-value: <0.00195% CI: [0.21, 0.53]MMRM
Comparison: Day 29p-value: <0.00195% CI: [0.23, 0.68]MMRM
Comparison: Day 57p-value: =0.00295% CI: [0.13, 0.55]MMRM
Comparison: Day 85p-value: =0.00295% CI: [0.15, 0.47]MMRM
Secondary
Mean Change From Baseline in Cat Allergen Quantity as Experienced by Participants During Exposure on Days 8, 29, 57, and 85
Cat Allergen Exposure Tolerated in ng = Minute Ventilation (L/min) x Allergen Concentration (ng/m3) x Time in EEU (minutes), where 1 L/min = 0.001 m3/min. The change in cat allergen quantity (tolerated exposure) from the baseline Cat Allergen Challenge, will be analyzed using a similar MMRM model with treatment, visit and treatment by-visit interaction as factors and the cat allergen quantity tolerated in the baseline Controlled Cat Allergen Challenge as a covariate.
Time frame: Days 8, 29, 57 and 85
Population: Full analysis set: included all randomized participants who received any investigational product and had completed the Day 8 Cat Allergen Challenge; Here n = number of evaluable participants analyzed at each time point
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Change From Baseline in Cat Allergen Quantity as Experienced by Participants During Exposure on Days 8, 29, 57, and 85 | Day 8 | 19.55 Nanograms (ng) | Standard Error 8.93 |
| Placebo | Mean Change From Baseline in Cat Allergen Quantity as Experienced by Participants During Exposure on Days 8, 29, 57, and 85 | Day 29 | 14.14 Nanograms (ng) | Standard Error 8.67 |
| Placebo | Mean Change From Baseline in Cat Allergen Quantity as Experienced by Participants During Exposure on Days 8, 29, 57, and 85 | Day 57 | 21.94 Nanograms (ng) | Standard Error 10.23 |
| Placebo | Mean Change From Baseline in Cat Allergen Quantity as Experienced by Participants During Exposure on Days 8, 29, 57, and 85 | Day 85 | 12.93 Nanograms (ng) | Standard Error 9.29 |
| REGN1908-1909 600 mg | Mean Change From Baseline in Cat Allergen Quantity as Experienced by Participants During Exposure on Days 8, 29, 57, and 85 | Day 85 | 54.03 Nanograms (ng) | Standard Error 8.94 |
| REGN1908-1909 600 mg | Mean Change From Baseline in Cat Allergen Quantity as Experienced by Participants During Exposure on Days 8, 29, 57, and 85 | Day 8 | 59.05 Nanograms (ng) | Standard Error 8.7 |
| REGN1908-1909 600 mg | Mean Change From Baseline in Cat Allergen Quantity as Experienced by Participants During Exposure on Days 8, 29, 57, and 85 | Day 57 | 55.38 Nanograms (ng) | Standard Error 9.93 |
| REGN1908-1909 600 mg | Mean Change From Baseline in Cat Allergen Quantity as Experienced by Participants During Exposure on Days 8, 29, 57, and 85 | Day 29 | 68.21 Nanograms (ng) | Standard Error 8.21 |
Comparison: Day 8p-value: =0.00395% CI: [14.36, 64.65]MMRM
Comparison: Day 29p-value: <0.00195% CI: [30.01, 78.12]MMRM
Comparison: Day 57p-value: =0.02395% CI: [4.79, 62.08]MMRM
Comparison: Day 85p-value: =0.00395% CI: [15.1, 67.09]MMRM
Secondary
Number of Non-Serious and Serious Treatment-Emergent Adverse Events (TEAEs) Through End of Study
Adverse events and serious adverse events were collected from the time of informed consent signature and then at each visit until the end of the study with the exception of symptoms that occurred in response to the EEU within 24 hours following the EEU.
Time frame: Baseline to 16 weeks
Population: Safety Analysis Set (SAF): included all participants who received any investigational product and were analyzed as treated.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Non-Serious and Serious Treatment-Emergent Adverse Events (TEAEs) Through End of Study | Non-serious TEAEs | 66 Events |
| Placebo | Number of Non-Serious and Serious Treatment-Emergent Adverse Events (TEAEs) Through End of Study | Serious TEAEs | 0 Events |
| REGN1908-1909 600 mg | Number of Non-Serious and Serious Treatment-Emergent Adverse Events (TEAEs) Through End of Study | Non-serious TEAEs | 76 Events |
| REGN1908-1909 600 mg | Number of Non-Serious and Serious Treatment-Emergent Adverse Events (TEAEs) Through End of Study | Serious TEAEs | 0 Events |
Secondary
Percent Change in Cat Allergen Quantity as Experienced by Participants During Exposure on Days 8, 29, 57, and 85
Cat Allergen Exposure Tolerated in ng = Minute Ventilation (L/min) x Allergen Concentration (ng/m3) x Time in EEU (minutes), where 1 L/min = 0.001 m3/min. The change in cat allergen quantity (tolerated exposure) from the baseline Cat Allergen Challenge, will be analyzed using a similar MMRM model with treatment, visit and treatment by-visit interaction as factors and the cat allergen quantity tolerated in the baseline Controlled Cat Allergen Challenge as a covariate.
Time frame: Days 8, 29, 57 and 85
Population: Full analysis set: included all randomized participants who received any investigational product and had completed the Day 8 Cat Allergen Challenge; Here n = number of evaluable participants analyzed at each time point
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change in Cat Allergen Quantity as Experienced by Participants During Exposure on Days 8, 29, 57, and 85 | Day 8 | 119.86 Percentage of change | Standard Error 73.22 |
| Placebo | Percent Change in Cat Allergen Quantity as Experienced by Participants During Exposure on Days 8, 29, 57, and 85 | Day 29 | 93.62 Percentage of change | Standard Error 71.48 |
| Placebo | Percent Change in Cat Allergen Quantity as Experienced by Participants During Exposure on Days 8, 29, 57, and 85 | Day 57 | 118.08 Percentage of change | Standard Error 69.58 |
| Placebo | Percent Change in Cat Allergen Quantity as Experienced by Participants During Exposure on Days 8, 29, 57, and 85 | Day 85 | 76.75 Percentage of change | Standard Error 82.08 |
| REGN1908-1909 600 mg | Percent Change in Cat Allergen Quantity as Experienced by Participants During Exposure on Days 8, 29, 57, and 85 | Day 85 | 317.76 Percentage of change | Standard Error 78.84 |
| REGN1908-1909 600 mg | Percent Change in Cat Allergen Quantity as Experienced by Participants During Exposure on Days 8, 29, 57, and 85 | Day 8 | 325.29 Percentage of change | Standard Error 70.79 |
| REGN1908-1909 600 mg | Percent Change in Cat Allergen Quantity as Experienced by Participants During Exposure on Days 8, 29, 57, and 85 | Day 57 | 301.11 Percentage of change | Standard Error 67.11 |
| REGN1908-1909 600 mg | Percent Change in Cat Allergen Quantity as Experienced by Participants During Exposure on Days 8, 29, 57, and 85 | Day 29 | 338.22 Percentage of change | Standard Error 68.26 |
Comparison: Day 8p-value: =0.04995% CI: [0.69, 410.17]MMRM
Comparison: Day 29p-value: =0.01795% CI: [45.6, 443.59]MMRM
Comparison: Day 57p-value: =0.06495% CI: [-11.29, 377.35]MMRM
Comparison: Day 85p-value: =0.03995% CI: [12.44, 469.57]MMRM
Secondary
Percent Change in Normalized Area Under the Curve (AUC) of Forced Expiratory Volume in 1 Second (FEV1) Induced by a Controlled Cat Allergen Challenge Over Exposure Interval From Baseline to Controlled Cat Allergen Challenge on Days 8, 29, 57, and 85
The AUC was analyzed by mixed-effect model repeated measures (MMRM) with the treatment, time, treatment-by-time interaction, and day of challenge as factors and baseline FEV1 AUC as a continuous covariate.
Time frame: Days 8, 29, 57, and 85
Population: Full analysis set; Here 'n' = number of evaluable participants analyzed at each time point. For each participant at each controlled cat allergen challenge, AUC was calculated over the time period of 0 to 2 hours, with last observation carried forward used to impute values out to 2 hours if the patients remained in EEU for less than 2 hours. The AUCs were calculated using the trapezoidal rule and were normalized by dividing by the length of time (2 hours).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change in Normalized Area Under the Curve (AUC) of Forced Expiratory Volume in 1 Second (FEV1) Induced by a Controlled Cat Allergen Challenge Over Exposure Interval From Baseline to Controlled Cat Allergen Challenge on Days 8, 29, 57, and 85 | Day 8 | 1.59 Percentage of change | Standard Error 2.58 |
| Placebo | Percent Change in Normalized Area Under the Curve (AUC) of Forced Expiratory Volume in 1 Second (FEV1) Induced by a Controlled Cat Allergen Challenge Over Exposure Interval From Baseline to Controlled Cat Allergen Challenge on Days 8, 29, 57, and 85 | Day 29 | 0.46 Percentage of change | Standard Error 3.6 |
| Placebo | Percent Change in Normalized Area Under the Curve (AUC) of Forced Expiratory Volume in 1 Second (FEV1) Induced by a Controlled Cat Allergen Challenge Over Exposure Interval From Baseline to Controlled Cat Allergen Challenge on Days 8, 29, 57, and 85 | Day 57 | 1.77 Percentage of change | Standard Error 3.55 |
| Placebo | Percent Change in Normalized Area Under the Curve (AUC) of Forced Expiratory Volume in 1 Second (FEV1) Induced by a Controlled Cat Allergen Challenge Over Exposure Interval From Baseline to Controlled Cat Allergen Challenge on Days 8, 29, 57, and 85 | Day 85 | 0.20 Percentage of change | Standard Error 3.28 |
| REGN1908-1909 600 mg | Percent Change in Normalized Area Under the Curve (AUC) of Forced Expiratory Volume in 1 Second (FEV1) Induced by a Controlled Cat Allergen Challenge Over Exposure Interval From Baseline to Controlled Cat Allergen Challenge on Days 8, 29, 57, and 85 | Day 85 | 12.73 Percentage of change | Standard Error 3.14 |
| REGN1908-1909 600 mg | Percent Change in Normalized Area Under the Curve (AUC) of Forced Expiratory Volume in 1 Second (FEV1) Induced by a Controlled Cat Allergen Challenge Over Exposure Interval From Baseline to Controlled Cat Allergen Challenge on Days 8, 29, 57, and 85 | Day 8 | 15.15 Percentage of change | Standard Error 2.5 |
| REGN1908-1909 600 mg | Percent Change in Normalized Area Under the Curve (AUC) of Forced Expiratory Volume in 1 Second (FEV1) Induced by a Controlled Cat Allergen Challenge Over Exposure Interval From Baseline to Controlled Cat Allergen Challenge on Days 8, 29, 57, and 85 | Day 57 | 14.07 Percentage of change | Standard Error 3.43 |
| REGN1908-1909 600 mg | Percent Change in Normalized Area Under the Curve (AUC) of Forced Expiratory Volume in 1 Second (FEV1) Induced by a Controlled Cat Allergen Challenge Over Exposure Interval From Baseline to Controlled Cat Allergen Challenge on Days 8, 29, 57, and 85 | Day 29 | 16.67 Percentage of change | Standard Error 3.43 |
p-value: <0.00195% CI: [6.35, 20.77]MMRM
p-value: =0.00295% CI: [6.18, 26.24]MMRM
p-value: =0.01695% CI: [2.4, 22.2]MMRM
p-value: =0.00895% CI: [3.43, 21.65]MMRM
Secondary
Time to EAR Upon Controlled Cat Allergen Challenge in an EEU on Days 29, 57, and 85
Time to EAR was defined as the time to a ≥20% reduction in FEV1 or when the participant voluntarily departed the EEU due to clinically significant allergic and/or asthmatic symptoms
Time frame: Days 29, 57 and 85
Population: Full analysis set: included all randomized participants who received any investigational product and had completed the Day 8 Cat Allergen Challenge. Here n = number of evaluable participants analyzed at each time point
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Time to EAR Upon Controlled Cat Allergen Challenge in an EEU on Days 29, 57, and 85 | Day 29 | 41 Minutes |
| Placebo | Time to EAR Upon Controlled Cat Allergen Challenge in an EEU on Days 29, 57, and 85 | Day 57 | 56 Minutes |
| Placebo | Time to EAR Upon Controlled Cat Allergen Challenge in an EEU on Days 29, 57, and 85 | Day 85 | 41 Minutes |
| REGN1908-1909 600 mg | Time to EAR Upon Controlled Cat Allergen Challenge in an EEU on Days 29, 57, and 85 | Day 29 | NA Minutes |
| REGN1908-1909 600 mg | Time to EAR Upon Controlled Cat Allergen Challenge in an EEU on Days 29, 57, and 85 | Day 57 | 232 Minutes |
| REGN1908-1909 600 mg | Time to EAR Upon Controlled Cat Allergen Challenge in an EEU on Days 29, 57, and 85 | Day 85 | NA Minutes |
Comparison: Day 29p-value: <0.000195% CI: [0.12, 0.48]Cox Hazard Model
Comparison: Day 57p-value: =0.022295% CI: [0.22, 0.89]Cox Hazard Model
Comparison: Day 85p-value: =0.000395% CI: [0.13, 0.56]Cox Hazard Model