E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective is to assess the reduction of allergic symptoms as measured by combined symptom and medication score (CSMS) during birch pollen season after a single dose of REGN5713-5714-5715 versus placebo. |
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E.2.2 | Secondary objectives of the trial |
• To assess the reduction of allergic symptoms and use of allergy-relieving medications after a single dose of REGN5713-5714-5715 versus placebo • To evaluate the safety and tolerability of REGN5713-5714-5715, including the incidence of hypersensitivity reactions and local injection site reactions • To evaluate the reduction in early allergic response to birch allergen after a single dose of REGN5713-5714-5715 versus placebo • To determine systemic exposure of total antibody (ie, free and antigen-bound) in the form of concentration of REGN5713, REGN5714, and REGN5715 in serum • To assess the immunogenicity to REGN5713, REGN5714, and REGN5715 in subjects after a single dose of REGN5713-5714-5715 • To evaluate “well days” |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Future Biomedical Research (Optional) Subjects who agree to participate in the future biomedical research (FBR) sub-study will be required to consent to this optional sub-study before samples are banked for FBR. Additional samples will be collected for FBR. Residual biomarker samples for study-related research, as well as unused PK and ADA samples, will be stored for up to 15 years after the final date of the database lock (or for a shorter time period if required per regional laws and regulations). The samples may be utilized for FBR that may or may not be directly related to the study, including being used as reference samples and assay development or validation. The results of these future biomedical research analyses will not be presented in the CSR.
Pharmacogenomic Analysis (Optional) Subjects who agree to participate in the genomics sub-study will be required to consent to this optional sub-study before collection of the samples. Whole blood samples for DNA extraction should be collected on day 1/baseline (predose), but can be collected at a later study visit. The purpose of the pharmacogenomic analyses is to identify genomic associations with clinical or biomarker response to REGN5713-5714-5715, other birch allergy clinical outcome measures and possible AEs. In addition, associations between genomic variants and prognosis or progression of birch allergy as well as related allergic diseases may also be studied. These data may be used or combined with data collected from other studies to identify and validate genomic markers related to the study drug, target pathway, or birch allergy and related diseases. |
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E.3 | Principal inclusion criteria |
1. Documented or subject-reported history of birch pollen-triggered allergic rhinitis symptoms, with or without conjunctivitis, for at least 2 years 2. Positive SPT with birch pollen extract in the screening period, as defined in protocol 3. Positive Allergen-specific IgE (sIgE) tests for birch pollen and Bet v 1 in the screening period, as defined in the protocol 4. Willing and able to comply with clinic visits and study-related procedures
NOTE: Other protocol defined inclusion criteria apply |
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E.4 | Principal exclusion criteria |
1. Participation in a prior REGN5713-5714-5715 clinical trial 2. Recurrent or chronic rhinitis or sinusitis not associated with birch pollen season, or due to daily contact with other allergens causing symptoms that are expected to coincide with birch pollen season, as assessed by the investigator 3. Subjects who anticipate major changes in allergen exposure in their home or work environments that are expected to coincide with study assessments, per investigator discretion 4. Persistent chronic or recurring acute infection requiring treatment with antibiotics, antivirals, or antifungals, or any untreated respiratory infections (at the discretion of the investigator) within 4 weeks prior to screening. Subjects may be re-evaluated for eligibility after symptoms resolve 5. Documentation of active SARS-CoV-2 infection Note: A subject with a documented, positive PCR or serology test for SARS-CoV-2 may be enrolled, provided that the subject has: • Recovered from COVID-19 (all COVID-19-related symptoms and major clinical findings which can potentially affect the safety of the patient should be resolved to baseline), and • Had 2 negative results from a health authority-authorized nucleic acid amplification (PCR) test for COVID-19 taken at least 48 hours apart 6. A clinical history of asthma with 2 or more asthma exacerbations requiring hospitalizations or systemic corticosteroids in the previous year 7. History of birch allergy immunotherapy, as defined in the protocol 8. Use of anti-IgE or other biological therapy in treatment of asthma or allergy within 6 months prior to screening
NOTE: Other protocol defined exclusion criteria apply |
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E.5 End points |
E.5.1 | Primary end point(s) |
The daily Combined symptom and medication score (CSMS) in subjects who receive a single dose of REGN5713-5714-5715 versus placebo |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Visit 2 to the end of Birch Pollen Season, approximately 28 weeks |
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E.5.2 | Secondary end point(s) |
1-3. Total symptom score (TSS), Total nasal symptom score (TNSS), and Total ocular symptom score (TOSS), averaged over the duration of the birch pollen season, in subjects who receive a single dose of REGN5713-5714-5715 versus placebo 4.Daily medication score (DMS), averaged over the duration of the birch pollen season, in subjects who receive a single dose of REGN5713-5714-5715 versus placebo 5-6. Incidence of Treatment-emergent adverse event (TEAEs) and serious TEAEs throughout the study 7-8. Change and percent change from baseline to the end of study in birch Skin prick test (SPT) mean wheal diameter in subjects who receive a single dose of REGN5713-5714-5715 versus placebo 9-11. Total REGN5713, REGN5714, and REGN5715 concentration in serum over the study duration 12-14. Incidence of treatment emergent anti-drug antibodies (ADAs) to REGN5713, REGN5714, or REGN 5715 throughout the study 15. The number of “well days”. “Well days” are defined as days when rescue medication is not utilized and the TSS is ≤2/18 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1 - 6. Up to Week 28 7-8. Visit 2 to the end of Birch Pollen Season, approximately 28 weeks 9-15. Up to Week 28 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of study is defined as the date the last subject completes the last study visit, withdraws from the study, or is lost to follow-up (ie, the study subject can no longer be contacted by the investigator). |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 7 |