Study to Assess the Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Effects of a Single Dose of REGN5713-5714-5715 in Healthy Adult Participants

Healthy Volunteers Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03969849
• Other study ID #: R5713-5714-5715-HV-1857
• Secondary ID: 2018-004681-34
• Status: Completed
• Phase: Phase 1
• Start date: June 3, 2019
• Est. completion date: March 27, 2020

Study information

• Verified date: April 2020
• Source: Regeneron Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 96
• Est. completion date: March 27, 2020
• Est. primary completion date: March 27, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• Birch Pollen Allergy
• Healthy Volunteers
• Rhinitis, Allergic, Seasonal

Intervention

Drug:
• REGN5713-5714-5715
Part A: Cohort 1 - 3: Single sequential ascending subcutaneous (SC) dose Part A: Cohort 4: Single intravenous (IV) dose Part B: Single SC dose
• Matching placebo
Part A: Cohort 1 - 3: Single sequential ascending subcutaneous (SC) dose Part A: Cohort 4: Single intravenous (IV) dose Part B: Single SC dose

Locations

Country	Name	City	State
Belgium	Regeneron Study Site	Antwerp
Belgium	Regeneron Study Site	Ghent
Belgium	Regeneron Study Site	Leuven

Sponsors (1)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence and severity of treatment-emergent adverse events (TEAEs)		Up to 16 Weeks
Primary	The number of participants with abnormal adverse events (AEs)		Up to 16 Weeks
Primary	The number of participants with abnormal vital signs	Vital signs include blood pressure, heart rate, body temperature, and respiratory rate	Up to 16 Weeks
Primary	The number of participants with abnormal 12-lead electrocardiograms (ECGs)		Up to 16 Weeks
Primary	The number or participants with abnormal physical examinations	The limited physical examination will include assessment of heart, lungs, abdomen, peripheral pulses, and skin	Up to 16 Weeks
Primary	The number of abnormal laboratory examination	Hematology, chemistry, urinalysis and pregnancy testing samples will be analyzed	Up to 16 Weeks
Primary	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	Up to 16 Weeks
Primary	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	Up to 16 Weeks
Primary	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.	Up to 16 Weeks
Primary	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.	Up to 16 Weeks
Primary	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.	Up to 16 Weeks
Primary	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.	Up to 16 Weeks
Secondary	Total concentration of REGN5713 in serum over time		Up to 16 Weeks
Secondary	Total concentration of REGN5714 in serum over time		Up to 16 Weeks
Secondary	Total concentration of REGN5715 in serum over time		Up to 16 Weeks
Secondary	Immunogenicity as measured by anti-drug antibodies (ADA) to REGN5713		Up to 16 Weeks
Secondary	Immunogenicity as measured by ADA to REGN5714		Up to 16 Weeks
Secondary	Immunogenicity as measured by ADA to REGN5715		Up to 16 Weeks
Secondary	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
Secondary	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
Secondary	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
Secondary	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