E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Allergic Rhino conjunctivitis due to Cat Allergy |
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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] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | HLGT |
E.1.2 | Classification code | 10001708 |
E.1.2 | Term | Allergic conditions |
E.1.2 | System Organ Class | 10021428 - Immune system disorders |
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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 |
To determine the efficacy of REGN1908-1909, as compared to placebo, to reduce allergic rhinitis/conjunctivitis symptoms and allergy rescue medication use during natural cat exposure |
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E.2.2 | Secondary objectives of the trial |
The key secondary objectives are: • The key secondary objectives are: • To assess the reduction of allergic symptoms and use of allergy rescue medications after treatment with REGN1908-1909 versus placebo, as measured by the individual components of the combined symptom and medication score (CSMS) • To assess health-related quality of life (HRQoL) as measured by the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ[S]) • To determine the efficacy of REGN1908-1909, as compared to placebo, to inhibit a wheal-and-flare response to a skin prick test (SPT) with cat allergen • To assess the durability of effect in allergic rhinitis and conjunctivitis symptom and medication scores after multiple doses of REGN 1908-1909 compared to placebo given every 12 weeks (Q12W) • To determine the efficacy following multiple doses of REGN1908-1909 compared to placebo at inhibiting a wheal-and-flare response to a skin prick test with cat allergen |
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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) Patients 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.
Pharmacogenomic Analysis (Optional) Patients who agree to participate in the genomics sub-study will be required to consent to this optional sub-study before collection of the samples. |
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E.3 | Principal inclusion criteria |
1. Generally healthy males and females who are 12 years and older at the time of screening. Note that for those countries where local regulations or approvals permit enrollment of adults only, subject recruitment will be restricted to those who are ≥18 years of age. 2. Weight must be ≥40 kg at the time of screening 3. Documented or patient reported history (for at least 2 years) of symptomatic cat allergen triggered allergic rhinitis with or without conjunctivitis and with or without asthma as defined in the protocol 4. At least 1 generally healthy cat (that is unlikely to die during the study) living in the home resulting in regular exposure 5. A daily total rhinitis/conjunctivitis symptom score (total symptom score [TSS]) of at least 8 of 18 during at least 8 days of the 15-day baseline assessment period and use of standard, therapeutic doses of pharmacotherapy for the treatment of allergic rhinoconjunctivitis on at least 8 days of the 15-day baseline assessment period 6. Willing and able to comply with clinic visits and study-related procedures 7. Provide informed consent signed by study patient or legally acceptable representative as described in the protocol 8. Able to understand and complete study-related questionnaires
Additional protocol-defined inclusion criteria apply |
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E.4 | Principal exclusion criteria |
1. History of significant multiple and/or severe allergies that would potentially interfere with the assessments during the baseline and 12week efficacy assessment periods or confound results, per investigator discretion, including significant rhinitis or sinusitis due to daily contact with other allergens causing symptoms that are expected to coincide with the baseline period or any of the efficacy assessment periods 2. Received REGN1908-1909 in a prior REGN1908-1909 clinical trial (receipt of placebo in a previous trial is allowed) 3. Active lung disease other than asthma 4. Forced expiratory volume (FEV)1 less than 70% of predicted at screening or randomization 5. Treatment with an investigational drug within 2 months or within 5 half-lives (if known), whichever is longer, prior to screening 6. Persistent chronic or recurring acute infection requiring treatment with antibiotics, antivirals, or antifungals, or any untreated respiratory infections within 4 weeks prior to screening. Patients may be reevaluated after resolution of symptoms and specified time duration 7. Any laboratory findings showing evidence of organ dysfunction or any clinically significant deviation from the normal range, as decided by the Investigator at the screening visit as defined in the protocol 8. Any medical illness, which in the judgment of the investigator could preclude participation in the study or in whom treatment with epinephrine or beta-2 agonists or systemic corticosteroids would pose an increased risk (eg, history of clinically significant cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, psychiatric or neurological disease etc.) 9. History of life-threatening asthma, defined as an asthma episode that required intubation, and/or was associated with hypercapnia, respiratory arrest, and/or hypoxic seizures 10. History of intensive care hospitalization for asthma within past 2 years 11. Positive serum human chorionic gonadotropin pregnancy test at the screening visit or randomization visit for women of childbearing 1. History of significant multiple and/or severe allergies that would potentially interfere with the assessments during the baseline and 12week efficacy assessment periods or confound results, per investigator potential (WOCBP) as described in the protocol
Additional protocol-defined exclusion criteria apply
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E.5 End points |
E.5.1 | Primary end point(s) |
Daily combined symptom and medication score (CSMS) averaged over the last 12 weeks of the treatment period in patients who receive REGN1908-1909 versus placebo |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
•1. Daily total nasal symptom score (TNSS), averaged over the last 12 weeks of treatment period, in patients who receive REGN1908-1909 versus placebo 2. Percent change from pre-treatment baseline in average CSMS, over the last 12 weeks of the treatment period, in patients who receive REGN1908-1909 versus placebo 3. Percent change from pre-treatment baseline in average TNSS, over the last 12 weeks of the treatment period, in patients who receive REGN1908-1909 versus placebo 4. Daily total symptom score (TSS), averaged over the last 12 weeks of the treatment period, in patients who receive REGN1908-1909 versus placebo 5. Percent change from pre-treatment baseline in average TSS, over the last 12 weeks of the treatment period, in patients who receive REGN1908-1909 versus placebo 6. Percent change from baseline to the end of treatment in cat SPT mean wheal diameter in patients who receive REGN1908-1909 versus placebo 7. Daily CSMS, averaged over the initial 12 weeks of the treatment period, in patients who receive REGN1908-1909 versus placebo 8. Daily TNSS, averaged over the initial 12 weeks of treatment period, in patients who receive REGN1908-1909 versus placebo 9. Percent change from pre-treatment baseline in average CSMS, over the initial 12 weeks of the treatment period, in patients who receive REGN1908-1909 versus placebo 10. Percent change from pre-treatment baseline in average TNSS, over the initial 12 weeks of the treatment period, in patients who receive REGN1908-1909 versus placebo 11. Percent change from pre-treatment baseline in average TSS, over the initial 12 weeks of the treatment period, in patients who receive REGN1908-1909 versus placebo 12. Daily TSS score, averaged over the initial 12 weeks of the treatment period, in patients who receive REGN1908-1909 versus placebo 13. Percent change from pre-treatment baseline in average TOSS, over the initial 12 weeks of the treatment period, in patients who receive REGN1908-1909 versus placebo 14. Daily total ocular symptom score (TOSS), averaged over the last 12 weeks of the treatment period, in patients who receive REGN1908-1909 versus placebo 15. Percent change from pre-treatment baseline in average TOSS, over the last 12 weeks of the treatment period, in patients who receive REGN1908-1909 versus placebo 16. Percent change in FEV1 in patients with asthma who receive REGN1908-1909 versus placebo 17. Percent change in FEV1 in patients with asthma who receive REGN1908-1909 versus placebo 18. Percent change in cat skin prick test (SPT) mean wheal diameter in patients who receive REGN1908-1909 versus placebo 19. Change in FEV1 in patients with asthma who receive REGN1908-1909 versus placebo 20. Change in FEV1 in patients with asthma who receive REGN1908-1909 versus placebo 21. Change in RQLQ(S)+12 in patients who receive REGN1908-1909 versus placebo 22. Daily medication score (DMS), averaged over the initial 12 weeks of the treatment period, in patients who receive REGN1908-1909 versus placebo 23. DMS, averaged over the last 12 weeks of the treatment period, in patients who receive REGN1908-1909 versus placebo 24. Percent change from pre-treatment baseline in average DMS, averaged over the last 12 weeks of the treatment period, in patients who receive REGN1908-1909 versus placebo 25. Percent change from baseline to end of study in cat SPT mean wheal diameter in patients who receive REGN1908-1909 versus placebo 26. Asthma daily symptom (ADS) score, averaged over the initial 12 weeks of the treatment period, using Asthma Daytime Symptom Diary (ADSD) and the Asthma Nighttime Symptom Diary (ANSD), in patients with asthma who receive REGN1908-1909 versus placebo 27. ADS score, averaged over the last 12 weeks of the treatment period, using ADSD and the ANSD, in patients with asthma who receive REGN1908-1909 versus placebo 28. Daily TOSS, averaged over the initial 12 weeks of the treatment period, in patients who receive REGN1908-1909 versus placebo 29. Change in Asthma Control Questionnaire 5 Question Version (ACQ-5) in patients with asthma who receive REGN1908-1909 versus placebo 30. Daily number of nighttime awakenings, averaged over the initial 12 weeks of the treatment period, in patients with asthma who receive REGN1908-1909 versus placebo 31. Daily number of nighttime awakenings, averaged over the last 12 weeks of the treatment period, in patients with asthma who receive REGN1908-1909 versus placebo 32. Incidence of treatment-emergent adverse events (TEAEs), adverse event of special interest (AESIs), and serious TEAEs throughout the study 33. Total REGN1908 and REGN1909 concentration in serum over the study duration 34. Incidence of treatment-emergent anti-drug antibodies (ADAs) to REGN1908 and REGN1909 throughout the study |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-5: Weeks 48 to 60 6. Week 60 7-13: Weeks 0 to 12 14-15: Weeks 48 to 60 16. Baseline to week 12 17. Baseline to week 60 18-19: Baseline to week 12 20-21: Change from baseline to week 60 22: Weeks 0 to 12 23-24: Weeks 48 to 60 25: Week 72 26: Weeks 0 to 12 27: Weeks 48 to 60 28: Weeks 0 to 12 29: Baseline to week 60 30: Weeks 0 to 12 31: Weeks 48 to 60 32-34: Weeks 0 to 72 |
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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 | No |
E.6.7 | Pharmacodynamic | No |
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 | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 15 |
E.8.5 | The trial involves multiple Member States | No |
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 |
Belgium |
Canada |
France |
Germany |
Poland |
United States |
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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 patient completes the last study visit or withdraws from the study, or is lost to follow-up (ie, the study patient 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 | 23 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 25 |