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

NCT03969849 | Completed Phase 1

• 2 other identifiers: R5713-5714-5715-HV-18572018-004681-34
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 3

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.

Conditions

Healthy Volunteers; Birch Pollen Allergy

Outcome Measures

Primary Outcomes (12)

• Incidence and severity of treatment-emergent adverse events (TEAEs)

  Up to 16 Weeks

• The number of participants with abnormal adverse events (AEs)

  Up to 16 Weeks

• The number of participants with abnormal vital signs

  Vital signs include blood pressure, heart rate, body temperature, and respiratory rate

  Up to 16 Weeks

• The number of participants with abnormal 12-lead electrocardiograms (ECGs)

  Up to 16 Weeks

• 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

• The number of abnormal laboratory examination

  Hematology, chemistry, urinalysis and pregnancy testing samples will be analyzed

  Up to 16 Weeks

• 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

• 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

• 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

• 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

• 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

• 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 Outcomes (10)

• Total concentration of REGN5713 in serum over time

  Up to 16 Weeks

• Total concentration of REGN5714 in serum over time

  Up to 16 Weeks

• Total concentration of REGN5715 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

Study Arms (5)

Part A: Cohort 1

EXPERIMENTAL

Part A: Cohort 1 randomized 3:1 will receive REGN5713-5714-5715 or matching placebo

Drug: REGN5713-5714-5715; Drug: Matching placebo

Part A: Cohort 2

EXPERIMENTAL

Part A: Cohort 2 randomized 3:1 will receive REGN5713-5714-5715 or matching placebo

Drug: REGN5713-5714-5715; Drug: Matching placebo

Part A: Cohort 3

EXPERIMENTAL

Part A: Cohort 3 randomized 3:1 will receive REGN5713-5714-5715 or matching placebo

Drug: REGN5713-5714-5715; Drug: Matching placebo

Part A: Cohort 4

EXPERIMENTAL

Part A: Cohort 4 randomized 3:1 will receive REGN5713-5714-5715 or matching placebo

Drug: REGN5713-5714-5715; Drug: Matching placebo

Part B

EXPERIMENTAL

Part B: Randomized 1:1 will receive REGN5713-5714-5715 or matching placebo in Healthy Participants with birch pollen allergy

Drug: REGN5713-5714-5715; Drug: Matching placebo

Interventions

REGN5713-5714-5715 DRUG

Part A: Cohort 1 - 3: Single sequential ascending subcutaneous (SC) dose Part A: Cohort 4: Single intravenous (IV) dose Part B: Single SC dose

Part A: Cohort 1; Part A: Cohort 2; Part A: Cohort 3; Part A: Cohort 4; Part B

Matching placebo DRUG

Part A: Cohort 1 - 3: Single sequential ascending subcutaneous (SC) dose Part A: Cohort 4: Single intravenous (IV) dose Part B: Single SC dose

Part A: Cohort 1; Part A: Cohort 2; Part A: Cohort 3; Part A: Cohort 4; Part B

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Regeneron Pharmaceuticals: lead

Study Sites (3)

Regeneron Study Site

Antwerp, Belgium

Location

Regeneron Study Site

Ghent, Belgium

Location

Regeneron Study Site

Leuven, Belgium

Location

Related Publications (1)

• 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.

  PMID: 34126156 DERIVED

Study Officials

• Clinical Trial Management

  Regeneron Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 28, 2019
• First Posted: May 31, 2019
• Study Start: June 3, 2019
• Primary Completion: March 27, 2020
• Study Completion: March 27, 2020
• Last Updated: April 28, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• 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.
• 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).

Locations

BE (3)