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 |
Atopic dermatitis / Eczema |
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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 is to assess the long-term safety of dupilumab administered in adult patients with AD. |
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E.2.2 | Secondary objectives of the trial |
The secondary objective of the study is to assess the immunogenicity of dupilumab in adult patients with AD, in the context of re-treatment, and to monitor efficacy parameters associated with long-term treatment. |
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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 |
Optional Genomics Sub-Study was removed from Protocol Amendment 06
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E.3 | Principal inclusion criteria |
A patient must meet the following criteria to be eligible for inclusion in the study:
1. Participation in a prior clinical trial of dupilumab for AD and met one of the following:
a. Received study treatment and adequately completed the assessments required for both the treatment and follow-up periods of the parent studies (except studies listed in b) as defined in the parent protocols; specifically, patients must complete the primary endpoint visit and at least
50% of the scheduled in-clinic visits and at-home assessments*). Patients who discontinued a parent study prematurely (ie, patients who did not complete the protocol-defined end-of-study visit) cannot enroll into this open-label extension study before the date when the end-of-study visit would have normally occurred. Completion of the entire follow-up period is not required for parent studies where the protocol specifically allows for an earlier transition into the open-label extension, in which case these requirements apply up to the point of this early transition.
* For at-home assessments (eg, patient reported outcomes by IVRS calls), patients who completed less than 50% of the assessments may be eligible if technical issues (eg, IVRS system malfunction) or other documented objective circumstances
contributed to missing assessments, subject to approval by the medical monitor.
b. Received study treatment in any dupilumab AD study that has completed last patient last visit irrespective of duration of participation,
provided that patients complied with their investigator's instructions.
c. Underwent screening in R668-AD-1334 (Liberty AD SOLO 1) or R668-AD-1416 (Liberty AD SOLO 2), but could not be randomized due to randomization closure.
These patients must have met the inclusion criteria for the Liberty AD SOLO studies that were applicable at the screening visit, specifically:
• Chronic AD, (according to American Academy of Dermatology Consensus Criteria [Eichenfield 2014]), that has been present for at least 3 years before the screening visit
• Eczema Area and Severity Index (EASI) score ≥16 at the screening visit
• Investigator's Global Assessment (IGA) score ≥3 (on the 0 to 4 IGA scale, in which 3 is moderate and 4 is severe) at the screening visit
• ≥10% body surface area (BSA) of AD involvement at the screening visit
• Documented recent history (within 6 months before the screening visit) of inadequate response to treatment with topical medications or for whom topical treatments are otherwise medically inadvisable (eg, because of important side effects or safety risks)*
*With the clarification notes provided in the SOLO protocols.
For these patients, the following criteria must also apply at the baseline visit in this open-label study:
• EASI score ≥16
• IGA score ≥3
• ≥10% BSA of AD involvement
2. Must be ≥18 years of age at screening
3. Willing and able to comply with all clinic visits and study-related procedures
4. Able to understand and complete study-related questionnaires
5. Provide signed informed consent |
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E.4 | Principal exclusion criteria |
A patient who meets any of the following criteria will be excluded from the study:
1. Patients who, during their participation in a previous dupilumab clinical trial, developed a serious adverse event (SAE) deemed related to dupilumab*, which in the opinion of the investigator or of the medical monitor could indicate that continued treatment with dupilumab may present an unreasonable risk for the patient.
2. Patients who, during their participation in a previous dupilumab clinical trial, developed an AE that was deemed related to dupilumab* and led to study treatment discontinuation, which in the opinion of the investigator or of the medical monitor could indicate that continued treatment with dupilumab may present an unreasonable risk for the patient.
3. Conditions in the previous dupilumab study consistent with protocoldefined criteria for permanent study drug discontinuation, if deemed
related to dupilumab* or led to investigator - or sponsor-initiated withdrawal of patient from the study (eg, non-compliance, inability to
complete study assessments, etc.) unless such conditions are considered resolved and of no further consequence – subject to medical monitor review and approval.
*Note for exclusion criteria # 1, 2, and 3: In studies that are still blinded, conditions deemed related to the study treatment will be considered related to dupilumab.
4. Treatment with an investigational drug, other than dupilumab, within 8 weeks or within 5 half-lives (if known), whichever is longer, before the baseline visit.
5. Treatment with immunosuppressive/immunomodulating drugs (eg, cyclosporine, mycophenolate-mofetil, IFN-γ, azathioprine, methotrexate, JAK inhibitors) within 5 half-lives 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 in the current study.
6. Treatment with immunomodulating biologics, other than dupilumab, within 5 half-lives (if known) or 16 weeks (whichever is longer) before the first dose in the open-label extension study.
7. Treatment with a live (attenuated) vaccine within 12 weeks before the baseline visit.
8. Planned or anticipated use of any prohibited medications and procedures during study treatment.
9. Any active infection requiring systemic treatment; patients with such infection must have their infection resolved at least 1 week before baseline to be eligible to enroll in the study.
10. Known or suspected immunodeficiency, including history of invasive opportunistic infections (eg, tuberculosis, histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis, aspergillosis) despite infection resolution, or otherwise recurrent infections of abnormal frequency as judged by the investigator.
11. Known history of human immunodeficiency virus (HIV) infection or HIV seropositivity (HIV testing is not required at screening for patients with a negative HIV result within the past 1 year prior to baseline).
12. Known history of positive hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), or hepatitis C antibody. If a patient
has a documented negative result for any of these tests within 1 year of baseline, that particular test is not required at screening. Patients with isolated positive HBcAb or with positive hepatitis C antibody may undergo additional tests and consultations, and may enter the study only if active hepatitis B infection or carrier status has been definitively ruled out, subject to medical monitor's written approval.
Exclusion criteria 13-23 (see study protocol)
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint in the study is the incidence and rate (events per patient-year) of treatment-emergent adverse events (TEAEs) through the last study visit. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Throughout the duration of the study |
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E.5.2 | Secondary end point(s) |
Key secondary endpoints:
- Incidence and rate (events per patient-year) of SAEs and AEs of special interest
- Proportion of patients with IGA = 0-1 at each visit
- Proportion of patients with EASI-75 (≥75% reduction from baseline in EASI scores) at each visit |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Throughout the duration of the study |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
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 | Yes |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
E.8.2.3 | Other | No |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 225 |
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 |
Hong Kong |
Japan |
Korea, Republic of |
New Zealand |
Singapore |
United States |
Austria |
Estonia |
Finland |
France |
Lithuania |
Poland |
Sweden |
Bulgaria |
Netherlands |
Romania |
Spain |
Czechia |
Germany |
Italy |
Belgium |
Denmark |
Hungary |
Ireland |
Russian Federation |
Slovakia |
United Kingdom |
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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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |