E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
Atopic dermatitis / Eczema |
|
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 |
|
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. |
|
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. |
|
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:
The purpose of the genomic analyses is to identify genomic associations with clinical or biomarker response to IL4-R α inhibition, immunology, inflammation, eosinophil driven diseases, and atopic diseases. |
|
E.3 | Principal inclusion criteria |
A patient must meet the following criteria to be eligible for inclusion in the study:
1. Underwent study treatment in a prior clinical trial of dupilumab for AD and met one of the following:
a. 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.
b. Received study treatment in one the following studies: R668-AD-0914, R668-AD-1026, R668-AD-1117, R668-AD-1021, and R668-AD-1121, irrespective of duration of participation, provided that patients complied with their investigator’s instructions.
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 |
|
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 protocol-defined 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.).
*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 1 week 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. Active chronic or acute infection requiring systemic treatment with antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 2 weeks before day 1 visit, or superficial skin infections within 1 week before the screening visit. NOTE: patients may be rescreened after the infection resolves.
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. Hepatitis testing is not required at screening for patients with a negative result within 1 year prior to baseline.
Exclusion criteria 13-23 (see study protocol)
|
|
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. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Throughout the duration of the study |
|
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 |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Throughout the duration of the study |
|
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 150 |
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 |
Estonia |
Finland |
France |
Lithuania |
Poland |
Sweden |
Bulgaria |
Spain |
Czechia |
Germany |
Italy |
Denmark |
Hungary |
United Kingdom |
|
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 0 |