Clinical trial NCT03969849: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Birch Pollen Allergy
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2019-05-31
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Incidence and severity of treatment-emergent adverse events (TEAEs)
timeFrame: Up to 16 Weeks
measure: The number of participants with abnormal adverse events (AEs)
timeFrame: Up to 16 Weeks
measure: The number of participants with abnormal vital signs
timeFrame: Up to 16 Weeks
measure: The number of participants with abnormal 12-lead electrocardiograms (ECGs)
timeFrame: Up to 16 Weeks
measure: The number or participants with abnormal physical examinations
timeFrame: Up to 16 Weeks
measure: The number of abnormal laboratory examination
timeFrame: Up to 16 Weeks
measure: Part B only - The number of participants with abnormal lung function using spirometry - forced vital capacity (FVC) litres (L)
timeFrame: Up to 16 Weeks
measure: Part B only - The number of participants with abnormal lung function using spirometry - forced expiratory volume in 1 second (FEV1)
timeFrame: Up to 16 Weeks
measure: Part B only - The number of participants with abnormal lung function using spirometry - FEV1/FVC (%)
timeFrame: Up to 16 Weeks
measure: Part B only - The number of participants with abnormal lung function using spirometry - peak expiratory flow (PEF) Litre/second (L/s)
timeFrame: Up to 16 Weeks
measure: Part B only - The number of participants with abnormal lung function using spirometry - forced expiratory flow 25 to 75 (L/s)
timeFrame: Up to 16 Weeks
measure: Part B only - The number of participants with poorly controlled asthma using asthma control test (ACT)
timeFrame: Up to 16 Weeks
Secondary outcomes:
measure: Total concentration of REGN5713 in serum over time
timeFrame: Up to 16 Weeks
measure: Total concentration of REGN5714 in serum over time
timeFrame: Up to 16 Weeks
measure: Total concentration of REGN5715 in serum over time
timeFrame: Up to 16 Weeks
measure: Immunogenicity as measured by anti-drug antibodies (ADA) to REGN5713
timeFrame: Up to 16 Weeks
measure: Immunogenicity as measured by ADA to REGN5714
timeFrame: Up to 16 Weeks
measure: Immunogenicity as measured by ADA to REGN5715
timeFrame: Up to 16 Weeks
measure: 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
timeFrame: At day 8, 29 and 57
measure: 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
timeFrame: At day 8, 29 and 57
measure: 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
timeFrame: At day 8, 29 and 57
measure: 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
timeFrame: At day 8, 29 and 57
Other outcomes:
Locations:
city: Antwerp
country: Belgium
facility: Regeneron Study Site
city: Ghent
country: Belgium
facility: Regeneron Study Site
city: Leuven
country: Belgium
facility: Regeneron Study Site
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References:
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.