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
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Regeneron Pharmaceuticals
- Enrollment
- 96
- Locations
- 1
- Primary Endpoint
- The number of participants with abnormal adverse events (AEs)
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 60 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
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
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.
Arms & Interventions
Part A: Cohort 4
Part A: Cohort 4 randomized 3:1 will receive REGN5713-5714-5715 or matching placebo
Intervention: Matching placebo (Drug)
Part A: Cohort 1
Part A: Cohort 1 randomized 3:1 will receive REGN5713-5714-5715 or matching placebo
Intervention: REGN5713-5714-5715 (Drug)
Part A: Cohort 1
Part A: Cohort 1 randomized 3:1 will receive REGN5713-5714-5715 or matching placebo
Intervention: Matching placebo (Drug)
Part A: Cohort 2
Part A: Cohort 2 randomized 3:1 will receive REGN5713-5714-5715 or matching placebo
Intervention: REGN5713-5714-5715 (Drug)
Part A: Cohort 2
Part A: Cohort 2 randomized 3:1 will receive REGN5713-5714-5715 or matching placebo
Intervention: Matching placebo (Drug)
Part A: Cohort 3
Part A: Cohort 3 randomized 3:1 will receive REGN5713-5714-5715 or matching placebo
Intervention: REGN5713-5714-5715 (Drug)
Part A: Cohort 3
Part A: Cohort 3 randomized 3:1 will receive REGN5713-5714-5715 or matching placebo
Intervention: Matching placebo (Drug)
Part A: Cohort 4
Part A: Cohort 4 randomized 3:1 will receive REGN5713-5714-5715 or matching placebo
Intervention: REGN5713-5714-5715 (Drug)
Part B
Part B: Randomized 1:1 will receive REGN5713-5714-5715 or matching placebo in Healthy Participants with birch pollen allergy
Intervention: REGN5713-5714-5715 (Drug)
Part B
Part B: Randomized 1:1 will receive REGN5713-5714-5715 or matching placebo in Healthy Participants with birch pollen allergy
Intervention: Matching placebo (Drug)
Outcomes
Primary Outcomes
The number of participants with abnormal adverse events (AEs)
Time Frame: Up to 16 Weeks
The number of participants with abnormal 12-lead electrocardiograms (ECGs)
Time Frame: Up to 16 Weeks
The number or participants with abnormal physical examinations
Time Frame: Up to 16 Weeks
The limited physical examination will include assessment of heart, lungs, abdomen, peripheral pulses, and skin
The number of participants with abnormal vital signs
Time Frame: Up to 16 Weeks
Vital signs include blood pressure, heart rate, body temperature, and respiratory rate
Part B only - The number of participants with poorly controlled asthma using asthma control test (ACT)
Time Frame: Up to 16 Weeks
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.
Incidence and severity of treatment-emergent adverse events (TEAEs)
Time Frame: Up to 16 Weeks
The number of abnormal laboratory examination
Time Frame: Up to 16 Weeks
Hematology, chemistry, urinalysis and pregnancy testing samples will be analyzed
Part B only - The number of participants with abnormal lung function using spirometry - forced expiratory volume in 1 second (FEV1)
Time Frame: Up to 16 Weeks
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 - forced expiratory flow 25 to 75 (L/s)
Time Frame: Up to 16 Weeks
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 abnormal lung function using spirometry - forced vital capacity (FVC) litres (L)
Time Frame: Up to 16 Weeks
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 - FEV1/FVC (%)
Time Frame: Up to 16 Weeks
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)
Time Frame: Up to 16 Weeks
Spirometry will be measured only in participants with a history of asthma prior to the NAC procedure. PEF is the maximum speed of expiration.
Secondary Outcomes
- Total concentration of REGN5715 in serum over time(Up to 16 Weeks)
- Total concentration of REGN5713 in serum over time(Up to 16 Weeks)
- Immunogenicity as measured by ADA to REGN5715(Up to 16 Weeks)
- 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(At day 8, 29 and 57)
- 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(At day 8, 29 and 57)
- Total concentration of REGN5714 in serum over time(Up to 16 Weeks)
- Immunogenicity as measured by anti-drug antibodies (ADA) to REGN5713(Up to 16 Weeks)
- Immunogenicity as measured by ADA to REGN5714(Up to 16 Weeks)
- 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(At day 8, 29 and 57)
- 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(At day 8, 29 and 57)