Trial Outcomes & Findings for Study in Cat-Allergic Patients With Asthma to Evaluate the Efficacy of a Single Dose of REGN1908-1909 to Reduce Bronchoconstriction Upon Cat Allergen Challenge (NCT NCT03838731)

NCT ID: NCT03838731

Last Updated: 2021-07-01

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

56 participants

Primary outcome timeframe

Day 8

Results posted on

2021-07-01

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure
Placebo
Participants received a single dose of matching placebo
REGN1908-1909 600 mg
Participants received a single 600 mg dose of REGN1908-1909
Overall Study
STARTED
27
29
Overall Study
COMPLETED
26
28
Overall Study
NOT COMPLETED
1
1

Reasons for withdrawal

Reasons for withdrawal
Measure
Placebo
Participants received a single dose of matching placebo
REGN1908-1909 600 mg
Participants received a single 600 mg dose of REGN1908-1909
Overall Study
Pregnancy
0
1
Overall Study
Withdrawal of consent
1
0

Baseline Characteristics

Study in Cat-Allergic Patients With Asthma to Evaluate the Efficacy of a Single Dose of REGN1908-1909 to Reduce Bronchoconstriction Upon Cat Allergen Challenge

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Placebo
n=27 Participants
Participants received a single dose of matching placebo
REGN1908-1909 600 mg
n=29 Participants
Participants received a single 600 mg dose of REGN1908-1909
Total
n=56 Participants
Total of all reporting groups
Age, Continuous
30.2 Years
STANDARD_DEVIATION 8.8 • n=5 Participants
28.4 Years
STANDARD_DEVIATION 7.1 • n=7 Participants
29.3 Years
STANDARD_DEVIATION 8.0 • n=5 Participants
Sex: Female, Male
Female
17 Participants
n=5 Participants
18 Participants
n=7 Participants
35 Participants
n=5 Participants
Sex: Female, Male
Male
10 Participants
n=5 Participants
11 Participants
n=7 Participants
21 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
1 Participants
n=5 Participants
1 Participants
n=7 Participants
2 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
26 Participants
n=5 Participants
28 Participants
n=7 Participants
54 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race/Ethnicity, Customized
American Indian or Alaska Native
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race/Ethnicity, Customized
Asian
0 Participants
n=5 Participants
1 Participants
n=7 Participants
1 Participants
n=5 Participants
Race/Ethnicity, Customized
Native Hawaiian or Other Pacific Islander
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race/Ethnicity, Customized
Black or African American
3 Participants
n=5 Participants
0 Participants
n=7 Participants
3 Participants
n=5 Participants
Race/Ethnicity, Customized
White
24 Participants
n=5 Participants
27 Participants
n=7 Participants
51 Participants
n=5 Participants
Race/Ethnicity, Customized
Other
0 Participants
n=5 Participants
1 Participants
n=7 Participants
1 Participants
n=5 Participants
Race/Ethnicity, Customized
Unknown or Not Reported
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants

PRIMARY outcome

Timeframe: Day 8

Population: Full analysis set: included all randomized participants who received any investigational product and had completed the Day 8 Cat Allergen Challenge.

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.

Outcome measures

Outcome measures
Measure
Placebo
n=27 Participants
Participants received a single dose of matching placebo
REGN1908-1909 600 mg
n=29 Participants
Participants received a single 600 mg dose of REGN1908-1909
Time to Early Asthmatic Response (EAR) Upon Controlled Cat Allergen Challenge in an Environmental Exposure Unit (EEU) on Day 8
51 Minutes
Interval 33.92 to 70.7
NA Minutes
Interval 130.87 to
The median time to EAR could not be estimated in the REGN1908-1909 arm at the day 8 visit since a majority of participants were able to tolerate the full 4 hours of cat allergen exposure, the maximum time allowed in the EEU per protocol, without experiencing an EAR (censored at 4 hours)

SECONDARY outcome

Timeframe: 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

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

Outcome measures

Outcome measures
Measure
Placebo
n=27 Participants
Participants received a single dose of matching placebo
REGN1908-1909 600 mg
n=29 Participants
Participants received a single 600 mg dose of REGN1908-1909
Time to EAR Upon Controlled Cat Allergen Challenge in an EEU on Days 29, 57, and 85
Day 29
41 Minutes
Interval 31.38 to 61.13
NA Minutes
Interval 131.22 to
Time to EAR, post-baseline, was censored at 4 hours if the participant remained in the EEU for the maximum time and did not experience an EAR. Baseline EEU maximum exposure was 2 hours.
Time to EAR Upon Controlled Cat Allergen Challenge in an EEU on Days 29, 57, and 85
Day 57
56 Minutes
Interval 40.52 to 80.63
232 Minutes
Interval 81.05 to
Time to EAR, post-baseline, was censored at 4 hours if the participant remained in the EEU for the maximum time and did not experience an EAR. Baseline EEU maximum exposure was 2 hours.
Time to EAR Upon Controlled Cat Allergen Challenge in an EEU on Days 29, 57, and 85
Day 85
41 Minutes
Interval 31.03 to 60.93
NA Minutes
Interval 90.97 to
Time to EAR, post-baseline, was censored at 4 hours if the participant remained in the EEU for the maximum time and did not experience an EAR. Baseline EEU maximum exposure was 2 hours.

SECONDARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure
Placebo
n=27 Participants
Participants received a single dose of matching placebo
REGN1908-1909 600 mg
n=29 Participants
Participants received a single 600 mg dose of REGN1908-1909
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
15.15 Percentage of change
Standard Error 2.50
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 3.60
16.67 Percentage of change
Standard Error 3.43
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
14.07 Percentage of change
Standard Error 3.43
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
12.73 Percentage of change
Standard Error 3.14

SECONDARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure
Placebo
n=27 Participants
Participants received a single dose of matching placebo
REGN1908-1909 600 mg
n=29 Participants
Participants received a single 600 mg dose of REGN1908-1909
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
0.38 Liters (L)
Standard Error 0.06
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
0.43 Liters (L)
Standard Error 0.08
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
0.34 Liters (L)
Standard Error 0.07
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
0.32 Liters (L)
Standard Error 0.08

SECONDARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure
Placebo
n=27 Participants
Participants received a single dose of matching placebo
REGN1908-1909 600 mg
n=29 Participants
Participants received a single 600 mg dose of REGN1908-1909
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
-0.49 Scores on a scale
Standard Error 0.38
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
-1.39 Scores on a scale
Standard Error 0.34
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
-0.83 Scores on a scale
Standard Error 0.43
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
-1.37 Scores on a scale
Standard Error 0.41

SECONDARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure
Placebo
n=25 Participants
Participants received a single dose of matching placebo
REGN1908-1909 600 mg
n=28 Participants
Participants received a single 600 mg dose of REGN1908-1909
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
-0.23 Scores on a scale
Standard Error 0.17
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
-0.43 Scores on a scale
Standard Error 0.14
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
-0.34 Scores on a scale
Standard Error 0.15
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
-0.51 Scores on a scale
Standard Error 0.10

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Outcome measures
Measure
Placebo
n=27 Participants
Participants received a single dose of matching placebo
REGN1908-1909 600 mg
n=29 Participants
Participants received a single 600 mg dose of REGN1908-1909
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
59.05 Nanograms (ng)
Standard Error 8.70
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
68.21 Nanograms (ng)
Standard Error 8.21
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
55.38 Nanograms (ng)
Standard Error 9.93
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
54.03 Nanograms (ng)
Standard Error 8.94

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Outcome measures
Measure
Placebo
n=27 Participants
Participants received a single dose of matching placebo
REGN1908-1909 600 mg
n=29 Participants
Participants received a single 600 mg dose of REGN1908-1909
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
325.29 Percentage of change
Standard Error 70.79
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
338.22 Percentage of change
Standard Error 68.26
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
301.11 Percentage of change
Standard Error 67.11
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
317.76 Percentage of change
Standard Error 78.84

SECONDARY outcome

Timeframe: Baseline to 16 weeks

Population: Safety Analysis Set (SAF): included all participants who received any investigational product and were analyzed as treated.

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.

Outcome measures

Outcome measures
Measure
Placebo
n=27 Participants
Participants received a single dose of matching placebo
REGN1908-1909 600 mg
n=29 Participants
Participants received a single 600 mg dose of REGN1908-1909
Number of Non-Serious and Serious Treatment-Emergent Adverse Events (TEAEs) Through End of Study
Non-serious TEAEs
66 Events
76 Events
Number of Non-Serious and Serious Treatment-Emergent Adverse Events (TEAEs) Through End of Study
Serious TEAEs
0 Events
0 Events

Adverse Events

Placebo

Serious events: 0 serious events
Other events: 19 other events
Deaths: 0 deaths

REGN1908-1909 600mg

Serious events: 0 serious events
Other events: 22 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Placebo
n=27 participants at risk
Participants received a single dose of matching placebo
REGN1908-1909 600mg
n=29 participants at risk
Participants received a single 600 mg dose of REGN1908-1909
Respiratory, thoracic and mediastinal disorders
Asthma
59.3%
16/27 • Number of events 35 • Baseline (day 1) to the end of study (week 16)
37.9%
11/29 • Number of events 19 • Baseline (day 1) to the end of study (week 16)
Respiratory, thoracic and mediastinal disorders
Asthma exercise induced
11.1%
3/27 • Number of events 3 • Baseline (day 1) to the end of study (week 16)
3.4%
1/29 • Number of events 1 • Baseline (day 1) to the end of study (week 16)
Respiratory, thoracic and mediastinal disorders
Rhinitis allergic
7.4%
2/27 • Number of events 2 • Baseline (day 1) to the end of study (week 16)
17.2%
5/29 • Number of events 5 • Baseline (day 1) to the end of study (week 16)
General disorders
Influenza like illness
14.8%
4/27 • Number of events 4 • Baseline (day 1) to the end of study (week 16)
10.3%
3/29 • Number of events 3 • Baseline (day 1) to the end of study (week 16)
General disorders
Injection site pain
3.7%
1/27 • Number of events 1 • Baseline (day 1) to the end of study (week 16)
6.9%
2/29 • Number of events 2 • Baseline (day 1) to the end of study (week 16)
Infections and infestations
Gastroenteritis
7.4%
2/27 • Number of events 2 • Baseline (day 1) to the end of study (week 16)
3.4%
1/29 • Number of events 1 • Baseline (day 1) to the end of study (week 16)
Infections and infestations
Nasopharyngitis
7.4%
2/27 • Number of events 2 • Baseline (day 1) to the end of study (week 16)
6.9%
2/29 • Number of events 2 • Baseline (day 1) to the end of study (week 16)
Nervous system disorders
Headache
7.4%
2/27 • Number of events 2 • Baseline (day 1) to the end of study (week 16)
17.2%
5/29 • Number of events 5 • Baseline (day 1) to the end of study (week 16)
Eye disorders
Conjunctivitis allergic
0.00%
0/27 • Baseline (day 1) to the end of study (week 16)
10.3%
3/29 • Number of events 3 • Baseline (day 1) to the end of study (week 16)
Gastrointestinal disorders
Nausea
0.00%
0/27 • Baseline (day 1) to the end of study (week 16)
6.9%
2/29 • Number of events 2 • Baseline (day 1) to the end of study (week 16)
Investigations
Blood creatine phosphokinase increased
0.00%
0/27 • Baseline (day 1) to the end of study (week 16)
6.9%
2/29 • Number of events 2 • Baseline (day 1) to the end of study (week 16)

Additional Information

Clinical Trials Administrator

Regeneron Pharmaceuticals, Inc.

Phone: 844-734-6643

Results disclosure agreements

  • Principal investigator is a sponsor employee The investigator has the right to independently publish study results from the investigator's site after a multi-center publication, or a defined period after the completion of the study by all sites. The investigator must provide the sponsor a copy of any such publication derived from the study for review and comment in advance of any submission, and delay publication, if requested, to allow the Sponsor to preserve its proprietary rights.
  • Publication restrictions are in place

Restriction type: OTHER