E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate to Severe Atopic Dermatitis |
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E.1.1.1 | Medical condition in easily understood language |
Moderate to Severe Atopic Dermatitis |
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E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10003639 |
E.1.2 | Term | Atopic dermatitis |
E.1.2 | System Organ Class | 100000004858 |
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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 |
The primary objective of the study is to assess the efficacy of REGN3500 monotherapy in atopic dermatitis (AD), as well as understand the dose-response relationship, compared with placebo treatment, in adult patients with moderate-to-severe AD. |
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E.2.2 | Secondary objectives of the trial |
-To assess the safety and tolerability of subcutaneous (SC) doses of REGN3500 monotherapy in adult patients with moderate-to-severe AD -To assess the pharmacokinetics (PK) of REGN3500 in adult patients with moderate-to-severe AD -To assess the immunogenicity of REGN3500 in adult patients with moderate-to-severe AD |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female, 18 to 75 years 2. Chronic AD, according to American Academy of Dermatology Consensus Criteria that has been present for at least 3 years before the screening visit 3. EASI score ≥16 at the screening and baseline visits 4. IGA score ≥3 (on the 0 to 4 IGA scale, in which 3 is moderate and 4 is severe) at screening and baseline visits 5. ≥10% BSA of AD involvement at the screening and baseline visits 6. Baseline peak Pruritus NRS score for maximum itch intensity ≥4 7. Documented recent history (within 6 months before the screening visit) of inadequate response to topical AD medication(s) or for whom topical treatments are medically inadvisable (eg, intolerance, because of important side effects, or safety risks). 8. Have applied a stable dose of topical bland emollient (moisturizer) at least twice daily for at least the 7 consecutive days immediately before the baseline visit (ie, baseline/randomization visit would be the eighth day; 9. Willing and able to comply with all clinic visits and study-related procedures 10. Provide informed consent signed by study patient or legally acceptable representative 11. Able to understand and complete study-related questionnaires |
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E.4 | Principal exclusion criteria |
1. Participation in a prior anti-IL-33 class medication clinical study 2. Body mass index <16 kg/m2 3. Treatment with an investigational drug within 8 weeks or within 5 half-lives (if known), whichever is longer, before the baseline visit 4. Having used any of the following treatments within 4 weeks before the baseline visit or any condition that, in the opinion of the investigator, is likely to require such treatment(s) during the first 4 weeks of study treatment:Immunosuppressive/immunomodulating drugs (eg, systemic corticosteroids, cyclosporine, mycophenolate-mofetil, IFN-γ, Janus kinase inhibitors, azathioprine, methotrexate, etc) Phototherapy for AD 5. Treatment with TCS, TCI, or topical crisaborole within 1 week before the baseline visit 6. Treatment with biologics as follows: Any cell-depleting agents including but not limited to rituximab: within 6 months before the baseline visit, or until lymphocyte count returns to normal, whichever is longer. Other biologics (including dupilumab): within 5 half-lives (if known) or 16 weeks prior to baseline visit, whichever is longer 7. Initiation of treatment of AD with prescription moisturizers or moisturizers containing additives such as ceramide, hyaluronic acid, urea, or filaggrin degradation products during the screening period 8. Regular use (more than 2 visits per week) of a tanning booth/parlor within 4 weeks of the baseline visit 9. Planned or anticipated use of any prohibited medications and procedures during study treatment 10. Treatment with a live (attenuated) vaccine within 12 weeks before the baseline visit 11. Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 2 weeks before the baseline visit, or superficial skin infections within 1 week before the baseline visit. 12. Known or suspected history of immunosuppression, including history of invasive opportunistic infections 13. History of human immunodeficiency virus (HIV) infection or positive HIV serology at screening 14. Positive with hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), or hepatitis C virus antibody (HCV Ab) at the screening visit 15. At baseline, presence of any conditions listed as criteria for study drug discontinuation 16. Presence of skin comorbidities that may interfere with study assessments 17. History of cancer, with the exceptions of: Patients with adequately treated basal cell carcinoma or carcinoma in situ of the cervix Patients with other malignancies that have been successfully treated for >10 years prior to screening where, in the judgement of both them investigator and the treating physician, appropriate follow-up has revealed no evidence of recurrence through time of screening. 18. Diagnosed active endoparasitic infections; suspected or high risk of endoparasitic infection, unless clinical and (if necessary) laboratory assessment have ruled out active infection before randomization 19. History of alcohol or drug abuse within 2 years of the screening visit 20. Severe concomitant illness(es) that, in the investigator’s judgment, would adversely affect the patient’s participation in the study. Examples include, but are not limited to, patients with short life expectancy, patients with uncontrolled diabetes (hemoglobin A1c [HbA1c] ≥9%), patients with uncontrolled cerebrocardio vascular conditions (eg, myocardial infarction [MI], unstable arterial hypertension, unstable angina, cerebrovascular accident, and stage III or IV cardiac failure according to the New York Heart Association classification), severe renal conditions (eg, patients on dialysis), hepatobiliary conditions (eg, Child-Pugh class B or C), neurological conditions (eg., demyelinating diseases), active major autoimmune diseases (eg, lupus, inflammatory bowel disease, rheumatoid arthritis, etc), other severe endocrinological, gastrointestinal, metabolic, pulmonary, or lymphatic diseases. 21. Any other medical or psychological condition (including relevant laboratory abnormalities at screening) that, in the opinion of the investigator, may suggest a new and/or insufficiently understood disease, may present an unreasonable risk to the study patient as a result of his/her participation in this clinical study, . 22. Planned or anticipated major surgical procedure during the patient’s participation in this study 23. Patient is a member of the investigational team or his/her immediate family 24. Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during the study 25. Women of childbearing potential 26. Known sensitivity to doxycycline and/or tetracycline or to any of the components of the investigational product formulation. 27. Patients who are committed to an institution by virtue of an order issued either by the judicial or the administrative authorities will be excluded from this study (as required by country regulations). |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint in the study is the percent change in Eczema Area and Severity Index (EASI) score from baseline to week 16 |
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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) |
The Efficacy secondary endpoints are: • Proportion of patients achieving EASI-50, EASI-75, and EASI-90 (≥50%, ≥75%, and ≥90% improvement from baseline) at week 16 • Absolute change in EASI scores from baseline to week 16 • Proportion of patients with both an IGA score of 0 or 1 (on a 5-point scale) and a reduction from baseline of ≥2 points at week 16 • Change (absolute and percent) from baseline to week 16 in weekly average of daily peak Pruritus Numerical Rating Scale (NRS) • Proportion of patients with improvement (reduction) of weekly average of daily peak pruritus NRS ≥4 from baseline at week 16 • Time to onset of effect on pruritus during the 16-week treatment period (≥4-point reduction of weekly average of daily peak Pruritus NRS from baseline) • Percent change from baseline to week 16 in SCORing Atopic Dermatitis (SCORAD) •Change from baseline to week 16 in percent Body Surface Area (BSA) of AD involvement Safety: •Incidence of treatment-emergent adverse events (TEAEs) from baseline through end of treatment (week 16) •Incidence of treatment-emergent serious adverse events (SAEs) from baseline through end of treatment (week 16) •Incidence of treatment-emergent adverse events of special interest (AESIs) from baseline through end of treatment (week 16) •Incidence of TEAEs from baseline through end of study (week 36) •Incidence of treatment-emergent SAEs from baseline through end of study (week 36) •Incidence of treatment-emergent AESIs from baseline through end of study (week 36) Pharmacokinetic (PK): •Concentrations of functional REGN3500 in serum by treatment regimen at each assessment time point from baseline to end of study (week 36)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | 18 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 45 |
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 |
Australia |
Canada |
Czech Republic |
France |
Germany |
Japan |
Korea, Republic of |
Poland |
Spain |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | No |
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 the study is defined as the date on which last subject completes the last visit |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |