A Phase 1, Randomized, Two-Part, Double-Blind, Placebo-Controlled, Dose-Escalation, Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Immunogenicity of AK120 in Healthy Subjects and Subjects With Moderate- to- Severe Atopic Dermatitis
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Akesobio Australia Pty Ltd
- Enrollment
- 80
- Locations
- 13
- Primary Endpoint
- Adverse events(AEs)/serious adverse events(SAEs)
Study Overview
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)
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Other
- Masking
- Triple (Participant, Care Provider, Investigator)
Masking Description
Double-Blind
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Subjects must meet all the following inclusion criteria (as applicable) to be eligible for participation in this study:
- •Willing and able to understand and sign an Informed Consent Form (ICF).
- •Women or men between 18 and 55 years of age, inclusive, at screening.
- •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.
- •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.
- •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.
- •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
- •Male or female, aged 18 to 65 years (inclusive) at time of Screening.
- •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.
- •EASI score ≥12 at the screening and baseline visits.
- •IGA score ≥3 at the screening and baseline visits.
- •BSA of AD involvement ≥10% at the screening and baseline visits.
- •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.
- •Subjects must be applying stable doses of an additive-free, basic bland emollient twice daily for at least 7 days before the baseline visit.
Exclusion Criteria
- •Subjects who meet any of the following exclusion criteria will not be enrolled in this study:
- •Clinically significant clinical safety laboratory result, or blood pressure or electrocardiogram (ECG) abnormalities.
- •Current acute infection or history of acute infection within 7 days prior to receipt of the study drug.
- •Have a recent history of conjunctivitis or keratitis within 6 months prior to screening.
- •History or complications of tuberculosis, or evidence of latent tuberculosis by QuantiFERON®-TB Gold screening.
- •Are positive for hepatitis B surface antigen, hepatitis C antibodies, or human immunodeficiency virus (HIV) at screening.
- •The washout period for prior drug therapy (eg. corticosteroids, immunosuppressive/immunomodulating, biologics, phototherapy, Chinese medicine，anti-infective agents) is inadequate.
- •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.
- •History of exposure to active TB, and/or history or current evidence of TB infection; and/or Chest X-ray showed old TB lesions at Screening or within 3 months before the Screening visit ..
- •Positive results at Screening for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb) or hepatitis C antibody with positive hepatitis C virus (HCV) RNA polymerase chain reaction; positive HIV serology at screening.
- •Any history of vernal keratoconjunctivitis (VKC) and 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
Arms & Interventions
Part 1:15mg cohort
Single dose of 15mg AK120 or placebo is administered subcutaneously to healthy subjects.
Intervention: AK120 or placebo- Part 1- Cohort 1 (Drug)
Part 1: 50mg cohort
Single dose of 50mg AK120 or placebo is administered subcutaneously to healthy subjects.
Intervention: AK120 or placebo- Part 1- Cohort 2 (Drug)
Part 1: 150mg cohort
Single dose of 150mg AK120 or placebo is administered subcutaneously to healthy subjects.
Intervention: AK120 or placebo- Part 1- Cohort 3 (Drug)
Part 1: 300 mg cohort
Single dose of 300mg AK120 or placebo is administered subcutaneously to healthy subjects.
Intervention: AK120 or placebo- Part 1- Cohort 4 (Drug)
Part 1: 600 mg cohort
Single dose of 600mg AK120 or placebo is administered subcutaneously to healthy subjects.
Intervention: AK120 or placebo- Part 1- Cohort 5 (Drug)
Part 2: low dose cohort
Multiple low doses of AK120 or placebo are administered subcutaneously to subjects with moderate- to- severe atopic dermatitis.
Intervention: AK120 or placebo- Part 2- Cohort 1 (Drug)
Part 2: medium dose cohort
Multiple medium doses of AK120 or placebo are administered subcutaneously to subjects with moderate- to- severe atopic dermatitis.
Intervention: AK120 or placebo- Part 2- Cohort 2 (Drug)
Part 2: high dose cohort
Multiple high doses of AK120 or placebo are administered subcutaneously to subjects with moderate- to- severe atopic dermatitis.
Intervention: AK120 or placebo- Part 2- Cohort 3 (Drug)
Part 2: Loading dose cohort
A loading dose followed by multiple high doses of AK120 or placebo are administered subcutaneously to subjects with moderate- to- severe atopic dermatitis.
Intervention: AK120 or placebo- Part 2- Cohort 4 (Drug)
Outcomes
Primary Outcomes
Adverse events(AEs)/serious adverse events(SAEs)
Time Frame: From signing of informed consent through through 12 weeks post-dose
Incidence of treatment emergent adverse events(AEs)/serious adverse events(SAEs)
Secondary Outcomes
- Area under the concentration-time curve (AUC)(From baseline through 12 weeks postdose)
- Anti-drug antibodies(ADAs)(From baseline through 12 weeks postdose)
- Maximum observed serum concentration (Cmax)(From baseline through 12 weeks post-dose)
- Thymus and activation regulated chemokine (TARC)/Chemokine Ligand 17(CCL17)(From baseline through 12 weeks post-dose)
- Investigator global assessment (IGA) (part 2)(From baseline through 12 weeks postdose)
- Change from baseline in Eczema Area and Severity Index (EASI) score(part 2)(From baseline through 12 weeks postdose)
- Change from baseline in body surface area (BSA) of AD involvement. (part 2)(From baseline through 12 weeks postdose)
- Pruritus-Numeric Rating Scale (P-NRS) (part 2)(From baseline through 12 weeks postdose)