A Study of AK120 (IL-4Rα) in Healthy Subjects and Subjects With Moderate- to- Severe Atopic Dermatitis

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

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

Study Overview

• Status: Completed
• Conditions: Atopic Dermatitis
• Intervention / Treatment: Drug: AK120 or placebo- Part 1- Cohort 1; Drug: AK120 or placebo- Part 1- Cohort 2; Drug: AK120 or placebo- Part 1- Cohort 3; Drug: AK120 or placebo- Part 1- Cohort 4; Drug: AK120 or placebo- Part 1- Cohort 5; Drug: AK120 or placebo- Part 2- Cohort 1; Drug: AK120 or placebo- Part 2- Cohort 2; Drug: AK120 or placebo- Part 2- Cohort 3; Drug: AK120 or placebo- Part 2- Cohort 4

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 Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Adelaide, Australia
    • CMAX Clinical Research
  • East Melbourne, Australia
    • Sinclair Dermatology
  • Kippa-Ring, Australia
    • Peninsula Specialist Centre
  • Randwick, Australia, 2031
    • Scientia Clinical Research Ltd
  • New South Wales
    • Botany, New South Wales, Australia, 2019
      • Emeritus Sydney
  • Victoria
    • Camberwell, Victoria, Australia, 3145
      • Emeritus Melbourne
• New Zealand
  • Auckland, New Zealand
    • Optimal Clinical Trials
  • Christchurch, New Zealand, 8011
    • Christchurch Clinical Studies Trust
  • Christchurch, New Zealand, 8013
    • Southern Clinical Trials - Christchurch
  • Havelock North, New Zealand, 4130
    • P3 Research Hawkes Bay
  • Tauranga, New Zealand, 3110
    • P3 Research Tauranga
  • Wellington, New Zealand, 6021
    • P3 Research Wellington
  • Auckland
    • Birkenhead, Auckland, New Zealand, 0626
      • Southern Clinical Trials - Waitemata

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 exclusion criteria will not be enrolled in this study:

Part 1:

1. Clinically significant clinical safety laboratory result, or blood pressure or electrocardiogram (ECG) abnormalities.
2. Current acute infection or history of acute infection within 7 days prior to receipt of the study drug.
3. Have a recent history of conjunctivitis or keratitis within 6 months prior to screening.
4. History or complications of tuberculosis, or evidence of latent tuberculosis by QuantiFERON®-TB Gold screening.
5. Are positive for hepatitis B surface antigen, hepatitis C antibodies, or human immunodeficiency virus (HIV) at screening.

Part 2:

1. The washout period for prior drug therapy (eg. corticosteroids, immunosuppressive/immunomodulating, biologics, phototherapy, Chinese medicine，anti-infective agents) is inadequate.
2. 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.
3. 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 ..
4. 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.
5. Any history of vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC) within 6 months before the baseline visit.
6. History of clinical parasite infection, recent or planned travel to an area with endemic parasite infection within 6 months before the Screening visit

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Triple

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1:15mg cohort; Single dose of 15mg AK120 or placebo is administered subcutaneously to healthy subjects.	Drug: AK120 or placebo- Part 1- Cohort 1; Single dose of 15mg AK120 or placebo is administered subcutaneously to healthy subjects
Experimental: Part 1: 50mg cohort; Single dose of 50mg AK120 or placebo is administered subcutaneously to healthy subjects.	Drug: AK120 or placebo- Part 1- Cohort 2; Single dose of 50mg AK120 or placebo is administered subcutaneously to healthy subjects
Experimental: Part 1: 150mg cohort; Single dose of 150mg AK120 or placebo is administered subcutaneously to healthy subjects.	Drug: AK120 or placebo- Part 1- Cohort 3; Single dose of 150mg AK120 or placebo is administered subcutaneously to healthy subjects
Experimental: Part 1: 300 mg cohort; Single dose of 300mg AK120 or placebo is administered subcutaneously to healthy subjects.	Drug: AK120 or placebo- Part 1- Cohort 4; Single dose of 300mg AK120 or placebo is administered subcutaneously to healthy subjects
Experimental: Part 1: 600 mg cohort; Single dose of 600mg AK120 or placebo is administered subcutaneously to healthy subjects.	Drug: AK120 or placebo- Part 1- Cohort 5; Single dose of 600mg AK120 or placebo is administered subcutaneously to healthy subjects
Experimental: Part 2: low dose cohort; Multiple low doses of AK120 or placebo are administered subcutaneously to subjects with moderate- to- severe atopic dermatitis.	Drug: AK120 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
Experimental: Part 2: medium dose cohort; Multiple medium doses of AK120 or placebo are administered subcutaneously to subjects with moderate- to- severe atopic dermatitis.	Drug: AK120 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
Experimental: Part 2: high dose cohort; Multiple high doses of AK120 or placebo are administered subcutaneously to subjects with moderate- to- severe atopic dermatitis.	Drug: AK120 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
Experimental: 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.	Drug: AK120 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events(AEs)/serious adverse events(SAEs)	Incidence of treatment emergent adverse events(AEs)/serious adverse events(SAEs)	From signing of informed consent through through 12 weeks post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Thymus and activation regulated chemokine (TARC)/Chemokine Ligand 17(CCL17)	Change from baseline in serum levels of thymus activation and regulated chemokine (TARC)/Chemokine Ligand 17 (CCL17) in serum	From baseline through 12 weeks post-dose
Maximum observed serum concentration (Cmax)	Maximum observed serum concentration (Cmax) of AK120	From baseline through 12 weeks post-dose
Area under the concentration-time curve (AUC)	Area under the concentration-time curve (AUC) of serum concentration of AK120	From baseline through 12 weeks postdose
Anti-drug antibodies(ADAs)	Number and percentage of subjects who develop detectable anti-drug antibodies(ADAs)	From baseline through 12 weeks postdose
Investigator global assessment (IGA) (part 2)	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.	From baseline through 12 weeks postdose
Pruritus-Numeric Rating Scale (P-NRS) (part 2)	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])	From baseline through 12 weeks postdose
Change from baseline in Eczema Area and Severity Index (EASI) score(part 2)	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.	From baseline through 12 weeks postdose
Change from baseline in body surface area (BSA) of AD involvement. (part 2)	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.	From baseline through 12 weeks postdose

Collaborators and Investigators

• Sponsor: Akesobio Australia Pty Ltd

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2020
• Primary Completion (Actual): October 29, 2021
• Study Completion (Actual): October 29, 2021

Study Registration Dates

• First Submitted: February 3, 2020
• First Submitted That Met QC Criteria: February 3, 2020
• First Posted (Actual): February 5, 2020

Study Record Updates

• Last Update Posted (Actual): August 17, 2022
• Last Update Submitted That Met QC Criteria: August 15, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Genetic; Hypersensitivity; Skin Diseases, Eczematous; Dermatitis; Eczema; Dermatitis, Atopic
• Other Study ID Numbers: AK120-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No