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] - 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 |
Efficacy To assess the effects of MEDI3506 compared with placebo on Atopic Dermatitis (AD) disease severity, in adult subjects with moderate to severe AD. |
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E.2.2 | Secondary objectives of the trial |
Efficacy To further assess the effects of MEDI3506 compared with placebo on AD disease severity and symptoms, in adult subjects with moderate to severe AD.
Safety To assess the safety and tolerability of MEDI3506 compared with placebo, in adult subjects with moderate to severe AD
PK To evaluate the PK of MEDI3506 in adult subjects with moderate to severe AD.
Immunogenicity To evaluate the immunogenicity of MEDI3506 in adult subjects with moderate to severe AD. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects must meet all of the following criteria:
If any criterion cannot be fully assessed at screening Visit 1 (eg, due to awaiting information from the subject's usual physician), the criterion must be fully assessed prior to randomization.
1 Written informed consent and any locally required authorization (eg, data privacy) prior to performing any protocol-related procedure, including screening. 2 Age 18 to 65 years inclusive at the time of consent. 3 Body mass index between 19.0 and 40.0 kg/m2 inclusive at screening Visit 1. 4 Documented history of chronic AD as defined using Hanifin and Rajka's criteria, for at least 1 year prior to screening Visit 1. 5 Meets at minimum 1 of the criteria, as follows: (a) A documented history, within the 6 months prior to screening Visit 1, of an IGA score of ≥ 3, despite treatment with daily, medium or high potency TCSs in the presence or absence of TCIs, applied for ≥ 4 weeks or for the maximum duration recommended by the product prescribing information, whichever is shorter, or (b) A documented history, within the 6 months prior to screening Visit 1, of requiring intermittent or continuous systemic corticosteroid therapy, (c) Subject intolerance to treatment with topical medications for AD, or (d) Topical medications are otherwise medically inadvisable (eg, due to important side effects or safety risks that outweigh the potential treatment benefits), as assessed by the investigator or by the physician who treats the subject's AD. 6 Able and willing to comply with the requirements of the protocol including ability to read, write, be fluent in the translated language of all subject facing questionnaires used at site, and use electronic devices. 7 AD that affects ≥ 10% of the body surface area (BSA) at both Visit 1 and Visit 3 (Day 1), as assessed by EASI. 8 An EASI score of ≥ 12 at Visit 1 and ≥ 16 at Visit 3 (Day 1). 9 An IGA score of ≥ 3 at both Visit 1 and Visit 3 (Day 1). 10 Female subjects, regardless of childbearing potential, must have negative pregnancy tests both at screening Visit 1 (serum pregnancy test) and pre-dose of investigational product at Visit 3 (Day 1; urine pregnancy test). 11 Female subjects of childbearing potential who are sexually active with a male partner must agree to use a highly effective method of contraception from screening until the end of the follow-up period at Visit 12 (Week 24) of the study. - In countries where spermicide is available, it is strongly recommended for the male partner of a female subject of childbearing potential to also use male condom plus spermicide throughout this period. - In countries where spermicide is not available, it is strongly recommended for the male partner of a female subject of childbearing potential to also use male condom throughout this period. 12 Female subjects of childbearing potential who are sexually active with a male partner must agree to use a highly effective method of contraception. - In countries where spermicide is available, male subjects who are sexually active with a female partner of childbearing potential must agree to use a male condom with spermicide and another highly effective method of contraception during the treatment and follow-up periods from Visit 3 (Day 1) through to Visit 12 (Week 24) of the study. - In countries where spermicide is not available, male subjects who are sexually active with a female partner of childbearing potential must agree to use a male condom and another highly effective method of contraception during the treatment and follow-up periods from Visit 3 (Day 1) through to Visit 12 (Week 24) of the study. 13 As confirmed from electronic diary (eDiary) entries, the subject has applied a stable dose of topical emollient (moisturizer) twice daily for ≥ 7 consecutive days immediately before baseline at Visit 3 (Day 1) with a minimum of (85%) compliance. |
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E.4 | Principal exclusion criteria |
1 Subjects with a recent history of or who have a positive test for infective hepatitis, HIV or unexplained jaundice, or subjects who have been treated for hepatitis B, hepatitis C, or HIV. For the hepatitis B testing (hepatitis B surface antigen [HBsAg], hepatitis B surface antibody [anti-HBs], and hepatitis B core antibody [anti-HBc]), any of the following would exclude the subject from the study: (a) Subjects positive for HBsAg. (b) Subjects positive for anti-HBc. Subjects with a history of hepatitis B vaccination without a history of hepatitis B are permitted. 2 Evidence of active or latent tuberculosis (TB). 3 N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) level greater than the upper limit of the laboratory reference range at screening Visit 1. 4 A left ventricular ejection fraction < 45% measured by echocardiogram during screening, between the time of signing informed consent and prior to randomization. 5 A family history of heart failure defined as either of the following: (a) ≥ 2 first degree relatives with clinically significant heart failure, or (b) ≥ 1 first degree relative with heart failure known to be heritable (eg, hypertrophic cardiomyopathy), unless inheritance is excluded by genetic testing. 6 Concurrent enrollment in another clinical study involving an investigational product. 7 Participated in a clinical study for a medical device within 3 months, prior to screening at Visit 1. 8 Subject is a participating investigator, sub-investigator, study coordinator, or employee of the participating site, or is a first-degree relative of the aforementioned. 9 Subject has been committed to an institution by virtue of an order issued either by the courts or by a public authority. 10 Any active medical or psychiatric condition, or other reason, prior to randomization, that, in the opinion of the investigator, would interfere with evaluation of the investigational product or interpretation of subject safety or study results. (a) Significant risk factors for COVID-19, such that study participation is not in the best interests of the subject in the opinion of the investigator. (b) Known or clinically suspected COVID-19 infection within 3 months of randomization. 11 Any other clinically relevant abnormal findings from physical examination (including vital signs and electrocardiogram [ECG]) or from safety laboratory analysis (including hematology, coagulation, serum chemistry, or urinalysis) between informed consent and randomization, that in the opinion of the investigator or medical monitor might compromise the safety of the subject in the study or interfere with evaluation of the investigational product. 12 A known history of severe reaction to any medication including biologic agents or human gamma globulin therapy. 13 Active dermatologic conditions that might confound the diagnosis of AD or would interfere with the assessment of the skin, for example scabies, seborrheic dermatitis, cutaneous lymphoma, or psoriasis. 14 Known active allergic or irritant contact dermatitis. 15 Known history of allergy or reaction to any component of the investigational product formulation,including hereditary fructose intolerance. 16 Pregnancy or intention to become pregnant during the course of the study, breastfeeding, or unwillingness to use a highly effective method of contraception throughout the study in female subjects of childbearing potential. 17 History of, or a reason to believe a subject has a history of, drug or alcohol abuse within the past 2 years prior to screening. 18 Major surgery within 8 weeks prior to screening at Visit 1, or planned inpatient surgery or hospitalization during the TCS/TCI wash out, treatment, or follow-up periods. 19 Donation of blood or blood products in excess of 500 mL within 3 months prior to screening Visit 1. 20 Current diagnosis of cancer. 21 History of cancer, except if treated with apparent success with curative therapy (response duration of > 5 years). 22 History of allogeneic bone marrow transplant. 23 History of herpes zoster within 3 months prior to randomization at Visit 3 (Day 1). 24 A helminth parasitic infection diagnosed within 6 months prior to randomization at Visit 3 (Day 1) that has not been treated, or has not responded to standard of care therapy. 25 Receiving any prohibited concomitant medications or therapies as specified in the protocol (Section 4.7.3). 26 History of a clinically significant non-skin infection within 4 weeks prior to Visit 3 (Day 1; including unexplained diarrhea) or clinical suspicion of a non-skin infection at the time of dosing of investigational product. 27 History of a skin infection that requires systemic antibiotics, antiviral medication, or antifungal medication for > 7 days within 4 weeks prior to Visit 3 (Day 1) or clinical suspicion of a skin-infection at time of dosing of investigational product. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy • Percent change from baseline to Week 16 in EASI score. |
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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) |
Efficacy • EASI: Percentage of subjects achieving a 90% reduction from baseline in EASI score (EASI 90) at Week 16. Percentage of subjects achieving a 75% reduction from baseline in EASI score (EASI 75) at Week 16. Percentage of subjects achieving a 50% reduction from baseline in EASI score (EASI 50) at Week 16. Percent change from baseline to Week 8 in EASI score. • Percentage of subjects achieving an IGA of 0 (clear) or 1 (almost clear) with at least a 2 grade reduction from baseline score at Week 16. • Peak pruritus NRS: Percentage of subjects achieving a reduction of ≥ 3 from baseline to Week 16 in weekly mean of daily peak pruritus NRS. • Peak pruritus NRS: Change from baseline to Week 16 in weekly mean of daily peak pruritus NRS. • Skin pain NRS: Change from baseline to Week 16 in weekly mean of daily peak skin pain NRS. • SCORAD: Percent change from baseline to Week 16. • PGI-S at Week 16. • Change from baseline to Week 16 in: % BSA affected by AD. 5-D itch. POEM. DLQI.
Safety During the treatment and follow-up periods: • TEAEs and TESAEs. • Vital signs. • Safety laboratory analysis. • ECGs. Left ventricular ejection fraction as measured by echocardiogram.
PK Serum MEDI3506 concentration profiles during the treatment and follow-up periods.
Immunogenicity Incidence of ADA during the treatment and follow-up periods. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Efficacy baseline and at week 8 and 16
PK and Immunogenicity baseline and at week 2,4,8,12,16,20,24
Safety Throughout 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 | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | 4 |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 26 |
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 |
United States |
Germany |
Poland |
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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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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 | 0 |
E.8.9.1 | In the Member State concerned days | 1 |
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 | 5 |