A Study to Evaluate the Efficacy and Safety of MEDI3506 in Adult Subjects with Moderate-to-severe Atopic Dermatitis

Phase 1

• Conditions: Atopic Dermatitis; MedDRA version: 21.1Level: LLTClassification code 10003639Term: Atopic dermatitisSystem Organ Class: 100000004858; Therapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]

• Registration Number: EUCTR2019-003304-12-GB
• Lead Sponsor: AstraZeneca AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-04-06
• Last Update Posted: 26 October 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 152

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 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 = 16 at both Visit 1 and 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 co

Exclusion Criteria

1 Subjects with a recent history of or who have a positive test for infective hepatitis 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 randomisation, 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 randomisation.
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 randomisation, 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.
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 s

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Efficacy<br>To assess the effects of MEDI3506 compared with placebo on Atopic Dermatitis (AD) disease severity, in adult subjects with moderate to severe AD.;Primary end point(s): Efficacy<br>• Percent change from baseline to Week 16 in EASI score.;Timepoint(s) of evaluation of this end point: baseline and at week 16;Secondary Objective: Efficacy<br>To further assess the effects of MEDI3506 compared with placebo on AD disease severity and symptoms, in adult subjects with moderate to severe AD.<br><br>Safety<br>To assess the safety and tolerability of MEDI3506 compared with placebo, in adult subjects with moderate to severe AD<br><br>PK<br>To evaluate the PK of MEDI3506 in adult subjects with moderate to severe AD.<br><br>Immunogenicity<br>To evaluate the immunogenicity of MEDI3506 in adult subjects with moderate to severe AD.