Clinical trial NCT05544591: Evaluation of 611 in Chinese Adults With Moderate to Severe Atopic Dermatitis
Official title: A Multi-Centered, Randomized, Double-Blinded, Placebo-Controlled Phase II Clinical Trial, to Evaluate the Efficacy and Safety of 611 in Chinese Adults With Moderate to Severe Atopic Dermatitis.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Dermatitis, Atopic
Lead sponsor: Sunshine Guojian Pharmaceutical (Shanghai) Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2022-09-16
Enrollment: 93
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of the study was to evaluate the efficacy and safety of 611 in chinese adults with moderate to severe atopic dermatitis.

Detailed description: The maximum study duration was 28 weeks per participants, including a screening period of up to 4 weeks, a 16-week randomized treatment period, and a 8-week follow-up period.

Eligibility criteria: Inclusion Criteria:

* Subject must be able to understand and comply with the requirements of the study. and must participate voluntarily and sign the written informed consent.
* Male or female adults ages 18 to 64 years old when signing the informed consent.
* AD (according to American Academy of Dermatology Consensus Criteria, 2014) that had been present for at least 1 years before the screening visit.
* Eczema Area and Severity Index (EASI) score greater than or equal to (\>=) 16 at the screening and baseline visits.
* Investigator's Global Assessment (IGA) score \>=3 (on the 0 to 4 IGA scale, in which 3 was moderate and 4 was severe) at the screening and baseline visits.
* Participants with \>=10 percent (%) body surface area (BSA) of AD involvement at the screening and baseline visits.
* Baseline Pruritus Numerical Rating Scale (NRS) average score for maximum itch intensity \>=4.
* Recent history (within 12 months before the screening visit) of inadequate response to treatment with topical medications or for whom topical treatments were otherwise medically inadvisable (e.g., because of important side effects or safety risks).
* Have applied a stable dose of topical emollient (moisturizer) twice daily for at least the 7 consecutive days immediately before the baseline visit.
* Female subjects of reproductive age (and their male partners) and male subjects (and their female partners) must use highly effective contraception throughout the study period and for at least 3 months after the last dose. The subjects had no plans to pregnancy, donate sperm or donate egg during the whole study period and for at least 3 months after the last dose.

Exclusion Criteria:

* Presence of skin comorbidities that may interfere with study assessments
* Presence of active endoparasitic infections; or suspected endoparasitic.
* Any history of vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC).
* History of malignancy within 5 years before the baseline visit, except completely treated in situ carcinoma of the cervix at least 1 year, completely treated and resolved non-metastatic squamous or basal cell carcinoma of the skin at least 1 year.
* Active chronic or acute infection requiring treatment with systemic anti-infective therapy within 2 weeks before the baseline visit, or superficial skin infections within 1 week before the baseline visit.
* Known or suspected history of immunosuppression, including history of invasive opportunistic infections (e.g., histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis, aspergillosis) despite infection resolution: or unusually frequent infections, per investigator judgment.
* Active TB, unless that was well documented that the participants had adequately treated.
* Any medical condition that, in the opinion of the investigator, is serious or unstable and may affect the subject's safety and/or prevent the subject from completing the study
* Patients who have received any of the following treatments: a) Treatment with topical drugs such as corticosteroids, topical calcineurin inhibitors, PDE inhibitors, or Janus kinase (JAK) inhibitors within 2 weeks before baseline; b) Treatment with systemic traditional Chinese medicine (TCM) within 4 weeks before baseline or treatment with topical TCM; c) Have undergone bleaching baths ≥ twice within 2 weeks before baseline; d) Treatment with systemic corticosteroids or other immunosuppressive/immunomodulating substances (e.g., cyclosporine, mycophenolate mofetil, azathioprine, methotrexate, interferon-gamma \[IFN-γ\], oral JAK inhibitors, compound glycyrrhizin, azathioprine, mycophenolate mofetil, or methotrexate,) within 4 weeks before baseline or 5 drug half-lives (if known), whichever is longer; e) Treatment with phototherapy (narrow band ultraviolet B \[NBUVB\], ultraviolet B \[UVB\], ultraviolet A1 \[UVA1\], psoralen + ultraviolet A \[PUVA\]), sunbed or any other light emitting device (LED) therapy within 4 weeks before baseline; f) Treatment with cell depletion agents (e.g., rituximab) within 6 months before baseline. Treatment with other biological agents (e.g., dupilumab) within 3 months before baseline or 5 drug half-lives (if known), whichever is longer; g) History of inadequate response to treatment with anti-IL-4 and/or IL13 agents (e.g., dupilumab), in the opinion of the investigator. h) Treatment with allergen specific immunotherapy (SIT) within 6 months before the screening visit. i) 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 (participants may continue using stable doses of such moisturizers if initiated before the screening visit).
* Presence of any one of the following lab abnormalities at screening or baseline: a) Total bilirubin \> 1.5 times the upper limit of normal (ULN); b) Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 2 ULN; c) Serum creatinine (Cr) \> 1.5×ULN; d) White blood cell count below the lower limit of normal (LLN) , was judged clinically significant by the investigator, and not suitable for inclusion in the study;
* HBsAg-positive with HBV DNA copy number beyond normal limit of the HBV DNA test, or HCV antibodies (HCV Ab)-positive with HCV RNA copy number beyond normal limit of the HCV RNA test, human immunodeficiency virus antibody (HIV Ab) positive, serum syphilis helix antibody (TP Ab) positive with syphilis helix titrating positive at screening;
* History of alcohol or drug abuse within 6 months before baseline.
* History of hypersensitivity to 611 or their excipients.
* Have been vaccinated with live (attenuated) vaccine within 2 months before baseline or planned during the study period;
* Have used any investigational drug/treatment within 8 weeks before baseline;
* Planned or anticipated major surgical procedure during the patient's participation in this study.
* Pregnant or lactating women, or subjects with pregnancy or lactation plans during the study period.
* Any reason which, in the opinion of investigator, would prevent the subject from participating in the study.

Primary outcomes:
measure: Number of Participants With Eczema Area and Severity Index (EASI) - 75 Response (>= 75% Improvement in Score From Baseline) at Week 16
timeFrame: Baseline, Week 16
Secondary outcomes:
measure: Number of Participants With EASI-50 (>=50% Improvement From Baseline) at Week 16
timeFrame: Baseline, Week 16
measure: Number of Participants With EASI-90 (>=90% Improvement From Baseline) at Week 16
timeFrame: Baseline, Week 16
measure: Number of Participants With Investigator's Global Assessment (IGA) Score of "0" or "1" and Improvement From Baseline of Greater Than or Equal to (>=) 2 Points From Baseline to Week 16
timeFrame: Baseline to Week 16
measure: Number of Participants Who Achieve Improvement of IGA Score by >=2 From Baseline to Week 16
timeFrame: Baseline to Week 16
measure: Number of Participants Who Achieved >=4 Points With Improvement From Baseline in Weekly Average of Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 16
timeFrame: Baseline to Week 16
measure: Number of Participants Who Achieved >=3 Points With Improvement From Baseline in Weekly Average of Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 16
timeFrame: Baseline to Week 16
measure: Percentage Change From Baseline to Week 16 in EASI Score
timeFrame: Baseline to Week 16
measure: Change From Baseline to Week 16 in Percent Body Surface Area (BSA) of AD Involvement
timeFrame: Baseline to Week 16
measure: Change From Baseline at Week 16 in Weekly Average of Pruritus NRS
timeFrame: Baseline to Week 16
measure: Change From Baseline to Week 16 in Dermatology Life Quality Index (DLQI) Total Score
timeFrame: Baseline to Week 16
measure: Change From Baseline to Week 16 in Patient Oriented Eczema Measure (POEM)
timeFrame: Baseline to Week 16
measure: Adverse events (AEs), measurement of vital signs，physical examination，electrocardiogram and laboratory tests at each visit.
timeFrame: Up to 24 Weeks
measure: Maximum Concentration (Cmax).
timeFrame: Baseline to Week 24.
measure: Minimum concentration (Cmin).
timeFrame: Baseline to Week 24.
measure: Time to Reach the Maximum Concentration (Tmax).
timeFrame: Baseline to Week 24.
measure: Area under the serum concentration-time curve from 0 to the time of the last quantifiable concentration (AUC0-last).
timeFrame: Baseline to Week 24.
measure: AUC to the end of the dosing period (AUC0-tau)
timeFrame: Baseline to Week 24.
measure: Clearance rate (CL/F).
timeFrame: Baseline to Week 24.
measure: Percentage of Participants With Anti-drug Antibodies and Neutralizing Antibodies.
timeFrame: Baseline to Week 24.
measure: Change in serum concentrations of Thymus and activation regulated chemokine (TARC)
timeFrame: Baseline to Week 24.
measure: Change in serum concentrations of IL-4
timeFrame: Baseline to Week 24.
measure: Change in serum concentrations of IL-13
timeFrame: Baseline to Week 24.
measure: Change in serum concentrations of IgE
timeFrame: Baseline to Week 24.
measure: Change in whole blood eosinophil counts
timeFrame: Baseline to Week 24.
measure: Change in serum concentrations of lactate dehydrogenase (LDH)
timeFrame: Baseline to Week 24.
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University People's Hospital
state: Beijing
city: Guangzhou
country: China
facility: Dermatology Hospital of Southern Medical University
state: Guangdong
city: Nanchang
country: China
facility: Dermatology Hospital of Jiangxi Province
state: Jiangxi
city: Hangzhou
country: China
facility: Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine
state: Zhejiang
city: Jinhua
country: China
facility: The Fourth Affiliated Hospital Zhejiang University School of Medicine
state: Zhejiang
Study officials:
References: