A Study to Evaluate the Safety, Pharmacokinetics and Efficacy of AK120 in Subjects With Atopic Dermatitis

Study Overview
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Brief Summary
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This is a randomized, double-blind, placebo-controlled, multicenter phase Ib/II clinical study to evaluate the safety, pharmacokinetics and efficacy of AK120 in the treatment of subjects with moderate to severe atopic dermatitis.

Detailed Description
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This is a randomized, double-blind, placebo-controlled, multicenter phase Ib/II clinical study to evaluate the safety, pharmacokinetics and efficacy of AK120 in subjects with moderate to severe atopic dermatitis.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Multicenter Phase Ib/II Clinical Study to Evaluate the Safety, Pharmacokinetics and Efficacy of AK120 in the Treatment of Subjects With Moderate to Severe Atopic Dermatitis

Conditions
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Atopic Dermatitis

Intervention / Treatment
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* Drug: AK120
* Drug: AK120
* Drug: Placebo
* Drug: AK120
* Drug: AK120
* Drug: AK120
* Drug: Placebo
* Drug: AK120
* Drug: AK120
* Drug: AK120


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female with age 18 - 75 years (inclusive). Atopic dermatitis (AD) diagnosed at least half an year before screening. Subject with EASI score ≥16, IGA ≥ 3, BSA ≥ 10% at screening and baseline. Subjects with a history of an inadequate response or medically inappropriate use of topical drug treatment within 6 months. Exclusion Criteria: Suffering from other inflammatory diseases that may affect efficacy outcomes (such as rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, scleroderma, inflammatory myopathy, mixed connective tissue disease, overlap syndrome, etc.). History of exposure to active TB, and/or history or current evidence of TB infection. Positive serology results at Screening for hepatitis B, hepatitis C or HIV. Any history of vernal keratoconjunctivitis (VKC) or atopic keratoconjunctivitis (AKC) within 6 months before the baseline visit. History of clinical parasite infection, recent or planned travel to an area with endemic parasite infection within 6 months before the Screening visit Any medical or psychiatric condition, laboratory, or ECG parameter which, in the opinion of the Investigator or the Sponsor's medical monitor, would place the subject at risk, interfere with participation in the study, or interfere with the interpretation of study results.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AK120 150 mg in phase Ib<br>subcutaneous injection once a week for 4 weeks. | Drug: AK120<br>* subcutaneous injection once a week<br>|
| Experimental: AK120 300mg in phase Ib<br>subcutaneous injection once a week for 4 weeks. | Drug: AK120<br>* subcutaneous injection once a week<br>|
| Placebo Comparator: Placebo Comparator: Placebo in phase Ib<br>subcutaneous injection once a week for 4 weeks. | Drug: Placebo<br>* subcutaneous injection once a week.<br>|
| Experimental: AK120 150mg in phase II<br>subcutaneous injection every 2 weeks for 50 weeks. | Drug: AK120<br>* subcutaneous injection every 2 weeks.<br>|
| Experimental: AK120 300mg in phase II<br>subcutaneous injection every 2 weeks for 50 weeks. | Drug: AK120<br>* subcutaneous injection every 2 weeks.<br>|
| Experimental: AK120 450mg in phase II<br>subcutaneous injection every 2 weeks for 50 weeks. | Drug: AK120<br>* subcutaneous injection every 2 weeks.<br>|
| Placebo Comparator: Placebo Comparator: Placebo in phase II<br>subcutaneous injection every 2 weeks, then crossover to AK120 Regimen 4 and Regimen 5, subcutaneous injection at week 16, after primary endpoint evaluation. | Drug: Placebo<br>* subcutaneous injection every 2 weeks for 16 weeks then crossover to AK120 Regimen 4 and Regimen 5.<br>|
| Experimental: AK120 150mg in phase II extension<br>subcutaneous injection every 2 weeks for 14 weeks. | Drug: AK120<br>* subcutaneous injection every 2 weeks<br>|
| Experimental: AK120 300mg in phase II extension<br>subcutaneous injection every 2 weeks for 14 weeks. | Drug: AK120<br>* subcutaneous injection every 2 weeks.<br>|
| Experimental: AK120 450mg in phase II extension<br>subcutaneous injection every 2 weeks for 14 weeks. | Drug: AK120<br>* subcutaneous injection every 2 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase Ib | Incidence of treatment emergent AE . An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product temporally associated with the use of study treatment, whether or not considered related to the study treatment. | Baseline to week 12 | 
| Phase Ib | T1/2 of AK120. Assessment of half-life(t1/2) of AK120. | Baseline to week 12 | 
| Phase Ib | AUC of AK120. Assessment of Area under the curve(AUC) of AK120 | Baseline to week 12 | 
| Phase Ib | Cmax of AK120. Assessment of Peak concentration(Cmax) of AK120 | Baseline to week 12 | 
| Phase Ib | Tmax of AK120. Assessment of Time to peak(Tmax) of AK120 | Baseline to week 12 | 
| Phase II | Percentage of subjects who achieved (Eczema Area and Severity Index)EASI-75 | at week 16 | 
| Phase II Extension Study | Incidence of treatment emergent AE . An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product temporally associated with the use of study treatment, whether or not considered related to the study treatment. | Baseline to week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase Ib | Percentage of subjects with detectable anti AK120 antibodies (ADA). | Baseline to week 12 | 
| Phase Ib | Percentage of subjects who achieved 0/1 in the Investigator's Global Assessment (IGA)(on a 6-point scale) . Lower score of IGA mean better outcome, higher score mean worse outcome | Baseline to week 12 | 
| Phase II | Percentage of subjects who achieved EASI-50 (≥50% improvement from baseline) /EASI-75 (≥75% improvement from baseline) response at each visit. Higher score mean better outcome, lower score mean worse outcome | Baseline to week 58 | 
| Phase II | Percentage change in EASI scores from baseline at each visit. Higher score mean better outcome, lower score mean worse outcome | Baseline to week 58 | 
| Phase II Extension Study | Percentage of subjects who achieved EASI-50 (≥50% improvement from baseline) /EASI-75 (≥75% improvement from baseline) response at each visit. Higher score mean better outcome, lower score mean worse outcome | Baseline to week 24 | 
| Phase II Extension Study | Percentage change in EASI scores from baseline at each visit. Higher score mean better outcome, lower score mean worse outcome | Baseline to week 24 |