Atopic Dermatitis
Conditions
Brief summary
A dose escalation, first-in-human study evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics and immunogenicity of AK120 in healthy subjects and subjects with moderate- to- severe atopic dermatitis
Detailed description
This is a phase 1, randomized, two-part, double-blind, placebo-controlled, dose-escalation, first-in-human study evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics and immunogenicity of AK120 in healthy subjects (part 1, single ascending dose) and subjects with moderate- to- severe atopic dermatitis(part 2, multiple ascending dose)
Interventions
DRUGAK120 or placebo- Part 1- Cohort 1
Single dose of 15mg AK120 or placebo is administered subcutaneously to healthy subjects
DRUGAK120 or placebo- Part 1- Cohort 2
Single dose of 50mg AK120 or placebo is administered subcutaneously to healthy subjects
DRUGAK120 or placebo- Part 1- Cohort 3
Single dose of 150mg AK120 or placebo is administered subcutaneously to healthy subjects
DRUGAK120 or placebo- Part 1- Cohort 4
Single dose of 300mg AK120 or placebo is administered subcutaneously to healthy subjects
DRUGAK120 or placebo- Part 1- Cohort 5
Single dose of 600mg AK120 or placebo is administered subcutaneously to healthy subjects
DRUGAK120 or placebo- Part 2- Cohort 1
Multiple low doses of AK120 or placebo are administered subcutaneously as a weekly dose for a total of four doses to subjects with moderate-to-severe atopic dermatitis
DRUGAK120 or placebo- Part 2- Cohort 2
Multiple medium doses of AK120 or placebo are administered subcutaneously as a weekly dose for a total of four doses to subjects with moderate-to-severe atopic dermatitis
DRUGAK120 or placebo- Part 2- Cohort 3
Multiple high doses of AK120 or placebo are administered subcutaneously as a weekly dose for a total of four doses to subjects with moderate-to-severe atopic dermatitis
DRUGAK120 or placebo- Part 2- Cohort 4
Multiple high doses of AK120 or placebo are administered subcutaneously as a bi-weekly dose for a total of three doses to subjects with moderate-to-severe atopic dermatitis.
Sponsors
Akesobio Australia Pty Ltd
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
OTHER
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Double-Blind
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
Major Inclusion Criteria: Subjects must meet all the following inclusion criteria (as applicable) to be eligible for participation in this study: Part 1: 1. Willing and able to understand and sign an Informed Consent Form (ICF). 2. Women or men between 18 and 55 years of age, inclusive, at screening. 3. Must have a calculated body mass index within 18.0 to 30.0 kg/m2 (inclusive) at screening, and a total body weight ≥50 kg for men or ≥45 kg for women at screening and Day -1 before randomization. 4. Women of childbearing potential who are sexually active must use one of the permitted methods of contraception from screening until at least 180 days after dosing of study medication. 5. Non-sterilized male subjects who are sexually active with a female partner of childbearing potential must use an effective method of contraception from Day 1 through 180 days after dosing of study medication. 6. Must, in the opinion of the Investigator, be in good general health based upon medical history, physical examination (including vital signs), and 12-lead ECG; and clinical laboratory tests Part 2: 1. Male or female, aged 18 to 65 years (inclusive) at time of Screening. 2. Chronic atopic dermatitis (AD) diagnosed by the revised Hanifin and Rajka criteria that has been present for at least 1 year before the Screening visit. 3. EASI score ≥12 at the screening and baseline visits. 4. IGA score ≥3 at the screening and baseline visits. 5. BSA of AD involvement ≥10% at the screening and baseline visits. 6. History of an inadequate response or medically inappropriate use of topical drug treatment, in the judgment of the Investigator, to AD treatment with a topical regimen of corticosteroids, phosphodiesterase inhibitors or calcineurin inhibitors or with phototherapy within 6 months of the Screening visit. 7. Subjects must be applying stable doses of an additive-free, basic bland emollient twice daily for at least 7 days before the baseline visit. Major
Exclusion criteria
Subjects who meet any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events(AEs)/serious adverse events(SAEs) | From signing of informed consent through through 12 weeks post-dose | Incidence of treatment emergent adverse events(AEs)/serious adverse events(SAEs) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Thymus and activation regulated chemokine (TARC)/Chemokine Ligand 17(CCL17) | From baseline through 12 weeks post-dose | Change from baseline in serum levels of thymus activation and regulated chemokine (TARC)/Chemokine Ligand 17 (CCL17) in serum |
| Maximum observed serum concentration (Cmax) | From baseline through 12 weeks post-dose | Maximum observed serum concentration (Cmax) of AK120 |
| Area under the concentration-time curve (AUC) | From baseline through 12 weeks postdose | Area under the concentration-time curve (AUC) of serum concentration of AK120 |
| Anti-drug antibodies(ADAs) | From baseline through 12 weeks postdose | Number and percentage of subjects who develop detectable anti-drug antibodies(ADAs) |
| Pruritus-Numeric Rating Scale (P-NRS) (part 2) | From baseline through 12 weeks postdose | The proportion of subjects with Pruritus-Numeric Rating Scale (P-NRS) improvement (reduction) from baseline of ≥ 3-point. Pruritus NRS is an assessment tool that is used to report the intensity of participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 \[0 = no itch; 10 = worst itch imaginable\]) |
| Change from baseline in Eczema Area and Severity Index (EASI) score(part 2) | From baseline through 12 weeks postdose | The EASI score was used to measure the severity and extent of atopic dermatitis (AD). The total EASI score range from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. |
| Change from baseline in body surface area (BSA) of AD involvement. (part 2) | From baseline through 12 weeks postdose | Body surface area determined by palm method where 1 palm is equivalent to 1%. Total body surface area ranges from 1% to 100%, with the higher body surface area reflecting the worse severity of AD. |
| Investigator global assessment (IGA) (part 2) | From baseline through 12 weeks postdose | The proportion of subjects with Investigator global assessment (IGA) 0 to 1 and subjects with IGA reduction from baseline of ≥ 2-point. IGA is an assessment scale used to determine severity of AD and clinical response to treatment on a static 6-point scale (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe；5 = very severe) based on erythema and papulation/infiltration. |
Countries
Australia, New Zealand
Outcome results
None listed