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

NCT04256174 | Completed Phase 1

• 1 other identifier: AK120-101
• Study Type: interventional
• Target: 80
• Locations: 2 countries
• Sites: 13

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

Conditions

Atopic Dermatitis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• Thymus and activation regulated chemokine (TARC)/Chemokine Ligand 17(CCL17)

  From baseline through 12 weeks post-dose

• Maximum observed serum concentration (Cmax)

  From baseline through 12 weeks post-dose

• Area under the concentration-time curve (AUC)

  From baseline through 12 weeks postdose

• Anti-drug antibodies(ADAs)

  From baseline through 12 weeks postdose

• Investigator global assessment (IGA) (part 2)

  From baseline through 12 weeks postdose

Study Arms (9)

Part 1:15mg cohort

EXPERIMENTAL

Single dose of 15mg AK120 or placebo is administered subcutaneously to healthy subjects.

Drug: AK120 or placebo- Part 1- Cohort 1

Part 1: 50mg cohort

EXPERIMENTAL

Single dose of 50mg AK120 or placebo is administered subcutaneously to healthy subjects.

Drug: AK120 or placebo- Part 1- Cohort 2

Part 1: 150mg cohort

EXPERIMENTAL

Single dose of 150mg AK120 or placebo is administered subcutaneously to healthy subjects.

Drug: AK120 or placebo- Part 1- Cohort 3

Part 1: 300 mg cohort

EXPERIMENTAL

Single dose of 300mg AK120 or placebo is administered subcutaneously to healthy subjects.

Drug: AK120 or placebo- Part 1- Cohort 4

Part 1: 600 mg cohort

EXPERIMENTAL

Single dose of 600mg AK120 or placebo is administered subcutaneously to healthy subjects.

Drug: AK120 or placebo- Part 1- Cohort 5

Part 2: low dose cohort

EXPERIMENTAL

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

Part 2: medium dose cohort

EXPERIMENTAL

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

Part 2: high dose cohort

EXPERIMENTAL

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

Part 2: Loading dose cohort

EXPERIMENTAL

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

Interventions

AK120 or placebo- Part 1- Cohort 1 DRUG

Single dose of 15mg AK120 or placebo is administered subcutaneously to healthy subjects

Part 1:15mg cohort

AK120 or placebo- Part 1- Cohort 2 DRUG

Single dose of 50mg AK120 or placebo is administered subcutaneously to healthy subjects

Part 1: 50mg cohort

AK120 or placebo- Part 1- Cohort 3 DRUG

Single dose of 150mg AK120 or placebo is administered subcutaneously to healthy subjects

Part 1: 150mg cohort

AK120 or placebo- Part 1- Cohort 4 DRUG

Single dose of 300mg AK120 or placebo is administered subcutaneously to healthy subjects

Part 1: 300 mg cohort

AK120 or placebo- Part 1- Cohort 5 DRUG

Single dose of 600mg AK120 or placebo is administered subcutaneously to healthy subjects

Part 1: 600 mg cohort

AK120 or placebo- Part 2- Cohort 1 DRUG

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

Part 2: low dose cohort

AK120 or placebo- Part 2- Cohort 2 DRUG

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

Part 2: medium dose cohort

AK120 or placebo- Part 2- Cohort 3 DRUG

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

Part 2: high dose cohort

AK120 or placebo- Part 2- Cohort 4 DRUG

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.

Part 2: Loading dose cohort

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Part 1:
• 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
• Part 2:
• 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.

You may not qualify if:

• Part 1:
• 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.
• Part 2:
• 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

Sponsors & Collaborators

• Akesobio Australia Pty Ltd: lead

Study Sites (13)

Emeritus Sydney

Botany, New South Wales, 2019, Australia

Location

Emeritus Melbourne

Camberwell, Victoria, 3145, Australia

Location

CMAX Clinical Research

Adelaide, Australia

Location

Sinclair Dermatology

East Melbourne, Australia

Location

Peninsula Specialist Centre

Kippa-Ring, Australia

Location

Scientia Clinical Research Ltd

Randwick, 2031, Australia

Location

Southern Clinical Trials - Waitemata

Birkenhead, Auckland, 0626, New Zealand

Location

Optimal Clinical Trials

Auckland, New Zealand

Location

Christchurch Clinical Studies Trust

Christchurch, 8011, New Zealand

Location

Southern Clinical Trials - Christchurch

Christchurch, 8013, New Zealand

Location

P3 Research Hawkes Bay

Havelock North, 4130, New Zealand

Location

P3 Research Tauranga

Tauranga, 3110, New Zealand

Location

P3 Research Wellington

Wellington, 6021, New Zealand

Location

Related Publications (1)

• Wynne CJ, Cole A, Lemech C, Wang G, Zhang Y, Chen B, Wang M, Li B, Xia M, Sinclair R. Safety, Pharmacokinetics and Preliminary Efficacy of IL4-Ralpha Monoclonal Antibody AK120 in Both Healthy and Atopic Dermatitis Subjects: A Phase I, Randomized, Two-Part, Double-Blind, Placebo-Controlled, Dose-Escalation, First-In-Human Clinical Study. Dermatol Ther (Heidelb). 2023 Oct;13(10):2357-2373. doi: 10.1007/s13555-023-01010-1. Epub 2023 Sep 5.

  PMID: 37668898 DERIVED

MeSH Terms

Conditions

Dermatitis, Atopic

Condition Hierarchy (Ancestors)

Skin Diseases, Genetic; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Dermatitis; Skin Diseases; Skin and Connective Tissue Diseases; Skin Diseases, Eczematous; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Double-Blind
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 3, 2020
• First Posted: February 5, 2020
• Study Start: June 15, 2020
• Primary Completion: October 29, 2021
• Study Completion: October 29, 2021
• Last Updated: August 17, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

AU (6); NZ (7)