Back to resultsStudy to Assess the Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Effects of a Single Dose of REGN5713-5714-5715 in Healthy Adult Participants
Primary Purpose
Healthy Volunteers, Birch Pollen Allergy
Status
Completed
Phase
Phase 1
Locations
Belgium
Study Type
Interventional
Intervention
REGN5713-5714-5715
Matching placebo
Sponsored by
About this trial
This is an interventional treatment trial for Healthy Volunteers
Eligibility Criteria
Key Inclusion Criteria:
- Participant is judged by the investigator to be in good health based on medical history, physical examination, vital sign measurements, and ECG performed prior to study drug dosing
- Participant is in good health based on laboratory safety testing obtained at the screening prior to study drug dosing
- Part B: Has a medical history of birch tree pollen-triggered allergic rhinitis (AR) symptoms with or without conjunctivitis (for at least 2 seasons) based on participant's recall
- Part B: Has positive skin prick test (SPT) with birch tree pollen extract (mean wheal diameter ≥5 mm greater than a negative control) in screening period
Key Exclusion Criteria:
- History of clinically significant cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, psychiatric, or neurological disease, as assessed by the investigator that may confound the results of the study or pose an additional risk to the participant by study participation
- Has any physical examination findings and/or history of any illness that, in the opinion of the study investigator, might confound the results of the study or pose an additional risk to the participant by study participation
- Participation in any clinical research study evaluating another investigational drug or therapy within 90 days or at least 5 half-lives (whichever is longer) for an investigational biologic drug, or at least 28 days for other investigational products, or within 6 months for immunotherapy prior to the screening visit of the current trial
- Pregnant or breastfeeding women
- Part B: Receipt of study drug REGN5713-5714-5715 in Part A
- Part B: Significant rhinitis or sinusitis outside of the birch pollen season or due to daily contact with other allergens causing symptoms, that is expected to coincide with the study NAC assessments as assessed by the investigator
- Part B: A clinical history of asthma requiring chronic medication such as regular, inhaled corticosteroids for >6 months per year
- Part B: History of birch allergy immunotherapy (SCIT, sublingual immunotherapy, or oral immunotherapy) in the 5 years prior to screening
NOTE: Other protocol defined inclusion/exclusion criteria apply.
Sites / Locations
- Regeneron Study Site
- Regeneron Study Site
- Regeneron Study Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
Part A: Cohort 1
Part A: Cohort 2
Part A: Cohort 3
Part A: Cohort 4
Part B
Arm Description
Part A: Cohort 1 randomized 3:1 will receive REGN5713-5714-5715 or matching placebo
Part A: Cohort 2 randomized 3:1 will receive REGN5713-5714-5715 or matching placebo
Part A: Cohort 3 randomized 3:1 will receive REGN5713-5714-5715 or matching placebo
Part A: Cohort 4 randomized 3:1 will receive REGN5713-5714-5715 or matching placebo
Part B: Randomized 1:1 will receive REGN5713-5714-5715 or matching placebo in Healthy Participants with birch pollen allergy
Outcomes
Primary Outcome Measures
Incidence and severity of treatment-emergent adverse events (TEAEs)
The number of participants with abnormal adverse events (AEs)
The number of participants with abnormal vital signs
Vital signs include blood pressure, heart rate, body temperature, and respiratory rate
The number of participants with abnormal 12-lead electrocardiograms (ECGs)
The number or participants with abnormal physical examinations
The limited physical examination will include assessment of heart, lungs, abdomen, peripheral pulses, and skin
The number of abnormal laboratory examination
Hematology, chemistry, urinalysis and pregnancy testing samples will be analyzed
Part B only - The number of participants with abnormal lung function using spirometry - forced vital capacity (FVC) litres (L)
Spirometry will be measured only in participants with a history of asthma prior to the NAC procedure. FVC is the total amount of air exhaled during the forced expiratory volume (FEV) test
Part B only - The number of participants with abnormal lung function using spirometry - forced expiratory volume in 1 second (FEV1)
Spirometry will be measured only in participants with a history of asthma prior to the NAC procedure. FEV in 1 second (FEV1) must be ≥80% predicted to perform the NAC. FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation
Part B only - The number of participants with abnormal lung function using spirometry - FEV1/FVC (%)
Spirometry will be measured only in participants with a history of asthma prior to the NAC procedure. FEV1 must be ≥80% predicted to perform the NAC.
Part B only - The number of participants with abnormal lung function using spirometry - peak expiratory flow (PEF) Litre/second (L/s)
Spirometry will be measured only in participants with a history of asthma prior to the NAC procedure. PEF is the maximum speed of expiration.
Part B only - The number of participants with abnormal lung function using spirometry - forced expiratory flow 25 to 75 (L/s)
Spirometry will be measured only in participants with a history of asthma prior to the NAC procedure. Forced expiratory flow during the mid (25 - 75%) portion of the FVC.
Part B only - The number of participants with poorly controlled asthma using asthma control test (ACT)
Performed prior to every NAC procedure in all participants. A multiple-choice questionnaire for patients with asthma, each choice is assigned a score 1-5. There are 5 questions to answer. The total score is calculated, ranging between 5 and 25. Lower scores indicate worse asthma control. Participants must have ACT ≥20 before undergoing the NAC.
Secondary Outcome Measures
Total concentration of REGN5713 in serum over time
Total concentration of REGN5714 in serum over time
Total concentration of REGN5715 in serum over time
Immunogenicity as measured by anti-drug antibodies (ADA) to REGN5713
Immunogenicity as measured by ADA to REGN5714
Immunogenicity as measured by ADA to REGN5715
Change in area under the curve (AUC) for TNSS (0 to 1 hour post-peak TNSS) in response to a nasal allergen challenge (NAC) from the pretreatment baseline TNSS AUC (0 to 1 hour post-peak TNSS) for REGN5713-5714-5715 as compared to placebo
Percent change in AUC for TNSS (0 to 1 hour post-peak TNSS) in response to a NAC from the pretreatment baseline TNSS AUC (0 to 1 hour post-peak TNSS) for REGN5713-5714-5715 as compared to placebo
Change in mean wheal diameters of the skin prick test with serial birch allergen titration from the pretreatment baseline for REGN5713-5714-5715 as compared to placebo
Percent change in mean wheal diameters of the skin prick test with serial birch allergen titration from the pretreatment baseline for REGN5713-5714-5715 as compared to placebo
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03969849
Brief Title
Study to Assess the Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Effects of a Single Dose of REGN5713-5714-5715 in Healthy Adult Participants
Official Title
A Two-Part, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Effects of a Single Dose of REGN5713-5714-5715 in Healthy Adult Subjects
Study Type
Interventional
2. Study Status
Record Verification Date
April 2020
Overall Recruitment Status
Completed
Study Start Date
June 3, 2019 (Actual)
Primary Completion Date
March 27, 2020 (Actual)
Study Completion Date
March 27, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Regeneron Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No
5. Study Description
Brief Summary
The primary objective of the study is to evaluate the safety and tolerability of REGN5713-5714-5715 in healthy adult participants.
The secondary objectives of the study are:
In Part A and Part B:
To characterize the concentration time profile of single doses of REGN5713-5714-5715 in healthy adults
To assess the immunogenicity of single dose of REGN5713-5714-5715.
In Part B:
To assess the inhibition of allergic symptoms as measured by total nasal symptom score (TNSS) provoked by a birch allergen nasal allergen challenge (NAC) in birch-sensitized allergic subjects after a single subcutaneous (SC) dose of REGN5713-5714-5715
To assess the skin test reactivity provoked by a skin prick test (SPT) with serial birch allergen titration after a single SC dose of REGN5713-5714-5715.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Healthy Volunteers, Birch Pollen Allergy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
96 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Part A: Cohort 1
Arm Type
Experimental
Arm Description
Part A: Cohort 1 randomized 3:1 will receive REGN5713-5714-5715 or matching placebo
Arm Title
Part A: Cohort 2
Arm Type
Experimental
Arm Description
Part A: Cohort 2 randomized 3:1 will receive REGN5713-5714-5715 or matching placebo
Arm Title
Part A: Cohort 3
Arm Type
Experimental
Arm Description
Part A: Cohort 3 randomized 3:1 will receive REGN5713-5714-5715 or matching placebo
Arm Title
Part A: Cohort 4
Arm Type
Experimental
Arm Description
Part A: Cohort 4 randomized 3:1 will receive REGN5713-5714-5715 or matching placebo
Arm Title
Part B
Arm Type
Experimental
Arm Description
Part B: Randomized 1:1 will receive REGN5713-5714-5715 or matching placebo in Healthy Participants with birch pollen allergy
Intervention Type
Drug
Intervention Name(s)
REGN5713-5714-5715
Intervention Description
Part A: Cohort 1 - 3: Single sequential ascending subcutaneous (SC) dose Part A: Cohort 4: Single intravenous (IV) dose Part B: Single SC dose
Intervention Type
Drug
Intervention Name(s)
Matching placebo
Intervention Description
Part A: Cohort 1 - 3: Single sequential ascending subcutaneous (SC) dose Part A: Cohort 4: Single intravenous (IV) dose Part B: Single SC dose
Primary Outcome Measure Information:
Title
Incidence and severity of treatment-emergent adverse events (TEAEs)
Time Frame
Up to 16 Weeks
Title
The number of participants with abnormal adverse events (AEs)
Time Frame
Up to 16 Weeks
Title
The number of participants with abnormal vital signs
Description
Vital signs include blood pressure, heart rate, body temperature, and respiratory rate
Time Frame
Up to 16 Weeks
Title
The number of participants with abnormal 12-lead electrocardiograms (ECGs)
Time Frame
Up to 16 Weeks
Title
The number or participants with abnormal physical examinations
Description
The limited physical examination will include assessment of heart, lungs, abdomen, peripheral pulses, and skin
Time Frame
Up to 16 Weeks
Title
The number of abnormal laboratory examination
Description
Hematology, chemistry, urinalysis and pregnancy testing samples will be analyzed
Time Frame
Up to 16 Weeks
Title
Part B only - The number of participants with abnormal lung function using spirometry - forced vital capacity (FVC) litres (L)
Description
Spirometry will be measured only in participants with a history of asthma prior to the NAC procedure. FVC is the total amount of air exhaled during the forced expiratory volume (FEV) test
Time Frame
Up to 16 Weeks
Title
Part B only - The number of participants with abnormal lung function using spirometry - forced expiratory volume in 1 second (FEV1)
Description
Spirometry will be measured only in participants with a history of asthma prior to the NAC procedure. FEV in 1 second (FEV1) must be ≥80% predicted to perform the NAC. FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation
Time Frame
Up to 16 Weeks
Title
Part B only - The number of participants with abnormal lung function using spirometry - FEV1/FVC (%)
Description
Spirometry will be measured only in participants with a history of asthma prior to the NAC procedure. FEV1 must be ≥80% predicted to perform the NAC.
Time Frame
Up to 16 Weeks
Title
Part B only - The number of participants with abnormal lung function using spirometry - peak expiratory flow (PEF) Litre/second (L/s)
Description
Spirometry will be measured only in participants with a history of asthma prior to the NAC procedure. PEF is the maximum speed of expiration.
Time Frame
Up to 16 Weeks
Title
Part B only - The number of participants with abnormal lung function using spirometry - forced expiratory flow 25 to 75 (L/s)
Description
Spirometry will be measured only in participants with a history of asthma prior to the NAC procedure. Forced expiratory flow during the mid (25 - 75%) portion of the FVC.
Time Frame
Up to 16 Weeks
Title
Part B only - The number of participants with poorly controlled asthma using asthma control test (ACT)
Description
Performed prior to every NAC procedure in all participants. A multiple-choice questionnaire for patients with asthma, each choice is assigned a score 1-5. There are 5 questions to answer. The total score is calculated, ranging between 5 and 25. Lower scores indicate worse asthma control. Participants must have ACT ≥20 before undergoing the NAC.
Time Frame
Up to 16 Weeks
Secondary Outcome Measure Information:
Title
Total concentration of REGN5713 in serum over time
Time Frame
Up to 16 Weeks
Title
Total concentration of REGN5714 in serum over time
Time Frame
Up to 16 Weeks
Title
Total concentration of REGN5715 in serum over time
Time Frame
Up to 16 Weeks
Title
Immunogenicity as measured by anti-drug antibodies (ADA) to REGN5713
Time Frame
Up to 16 Weeks
Title
Immunogenicity as measured by ADA to REGN5714
Time Frame
Up to 16 Weeks
Title
Immunogenicity as measured by ADA to REGN5715
Time Frame
Up to 16 Weeks
Title
Change in area under the curve (AUC) for TNSS (0 to 1 hour post-peak TNSS) in response to a nasal allergen challenge (NAC) from the pretreatment baseline TNSS AUC (0 to 1 hour post-peak TNSS) for REGN5713-5714-5715 as compared to placebo
Time Frame
At day 8, 29 and 57
Title
Percent change in AUC for TNSS (0 to 1 hour post-peak TNSS) in response to a NAC from the pretreatment baseline TNSS AUC (0 to 1 hour post-peak TNSS) for REGN5713-5714-5715 as compared to placebo
Time Frame
At day 8, 29 and 57
Title
Change in mean wheal diameters of the skin prick test with serial birch allergen titration from the pretreatment baseline for REGN5713-5714-5715 as compared to placebo
Time Frame
At day 8, 29 and 57
Title
Percent change in mean wheal diameters of the skin prick test with serial birch allergen titration from the pretreatment baseline for REGN5713-5714-5715 as compared to placebo
Time Frame
At day 8, 29 and 57
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Key Inclusion Criteria:
Participant is judged by the investigator to be in good health based on medical history, physical examination, vital sign measurements, and ECG performed prior to study drug dosing
Participant is in good health based on laboratory safety testing obtained at the screening prior to study drug dosing
Part B: Has a medical history of birch tree pollen-triggered allergic rhinitis (AR) symptoms with or without conjunctivitis (for at least 2 seasons) based on participant's recall
Part B: Has positive skin prick test (SPT) with birch tree pollen extract (mean wheal diameter ≥5 mm greater than a negative control) in screening period
Key Exclusion Criteria:
History of clinically significant cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, psychiatric, or neurological disease, as assessed by the investigator that may confound the results of the study or pose an additional risk to the participant by study participation
Has any physical examination findings and/or history of any illness that, in the opinion of the study investigator, might confound the results of the study or pose an additional risk to the participant by study participation
Participation in any clinical research study evaluating another investigational drug or therapy within 90 days or at least 5 half-lives (whichever is longer) for an investigational biologic drug, or at least 28 days for other investigational products, or within 6 months for immunotherapy prior to the screening visit of the current trial
Pregnant or breastfeeding women
Part B: Receipt of study drug REGN5713-5714-5715 in Part A
Part B: Significant rhinitis or sinusitis outside of the birch pollen season or due to daily contact with other allergens causing symptoms, that is expected to coincide with the study NAC assessments as assessed by the investigator
Part B: A clinical history of asthma requiring chronic medication such as regular, inhaled corticosteroids for >6 months per year
Part B: History of birch allergy immunotherapy (SCIT, sublingual immunotherapy, or oral immunotherapy) in the 5 years prior to screening
NOTE: Other protocol defined inclusion/exclusion criteria apply.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trial Management
Organizational Affiliation
Regeneron Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Regeneron Study Site
City
Antwerp
Country
Belgium
Facility Name
Regeneron Study Site
City
Ghent
Country
Belgium
Facility Name
Regeneron Study Site
City
Leuven
Country
Belgium
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
All individual participant data (IPD) that underlie publicly available results will be considered for sharing
IPD Sharing Time Frame
Individual anonymized participant data will be considered for sharing once the indication has been approved by a regulatory body, if there is legal authority to share the data and there is not a reasonable likelihood of participant re-identification.
IPD Sharing Access Criteria
Qualified researchers may request access to anonymized patient level data or aggregate study data when Regeneron has received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc) for the product and indication, has the legal authority to share the data, and has made the study results publicly available (eg, scientific publication, scientific conference, clinical trial registry).
IPD Sharing URL
https://vivli.org/
Citations:
PubMed Identifier
34126156
Citation
Gevaert P, De Craemer J, De Ruyck N, Rottey S, de Hoon J, Hellings PW, Volckaert B, Lesneuck K, Orengo JM, Atanasio A, Kamal MA, Abdallah H, Kamat V, Dingman R, DeVeaux M, Ramesh D, Perlee L, Wang CQ, Weinreich DM, Herman G, Yancopoulos GD, O'Brien MP. Novel antibody cocktail targeting Bet v 1 rapidly and sustainably treats birch allergy symptoms in a phase 1 study. J Allergy Clin Immunol. 2022 Jan;149(1):189-199. doi: 10.1016/j.jaci.2021.05.039. Epub 2021 Jun 11.
Results Reference
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Study to Assess the Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Effects of a Single Dose of REGN5713-5714-5715 in Healthy Adult Participants
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