Clinical trial NCT04256174: A Study of AK120 (IL-4Rα) in Healthy Subjects and Subjects With Moderate- to- Severe Atopic Dermatitis
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Atopic Dermatitis
Lead sponsor: Akeso
Sponsor class: INDUSTRY
First posted: 2020-02-05
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: OTHER

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)

Eligibility 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 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

Primary outcomes:
measure: Adverse events(AEs)/serious adverse events(SAEs)
timeFrame: From signing of informed consent through through 12 weeks post-dose
Secondary outcomes:
measure: Thymus and activation regulated chemokine (TARC)/Chemokine Ligand 17(CCL17)
timeFrame: From baseline through 12 weeks post-dose
measure: Maximum observed serum concentration (Cmax)
timeFrame: From baseline through 12 weeks post-dose
measure: Area under the concentration-time curve (AUC)
timeFrame: From baseline through 12 weeks postdose
measure: Anti-drug antibodies(ADAs)
timeFrame: From baseline through 12 weeks postdose
measure: Investigator global assessment (IGA) (part 2)
timeFrame: From baseline through 12 weeks postdose
measure: Pruritus-Numeric Rating Scale (P-NRS) (part 2)
timeFrame: From baseline through 12 weeks postdose
measure: Change from baseline in Eczema Area and Severity Index (EASI) score(part 2)
timeFrame: From baseline through 12 weeks postdose
measure: Change from baseline in body surface area (BSA) of AD involvement. (part 2)
timeFrame: From baseline through 12 weeks postdose
Other outcomes:
Locations:
city: Botany
country: Australia
facility: Emeritus Sydney
state: New South Wales
city: Camberwell
country: Australia
facility: Emeritus Melbourne
state: Victoria
city: Adelaide
country: Australia
facility: CMAX Clinical Research
city: East Melbourne
country: Australia
facility: Sinclair Dermatology
city: Kippa-Ring
country: Australia
facility: Peninsula Specialist Centre
city: Randwick
country: Australia
facility: Scientia Clinical Research Ltd
city: Birkenhead
country: New Zealand
facility: Southern Clinical Trials - Waitemata
state: Auckland
city: Auckland
country: New Zealand
facility: Optimal Clinical Trials
city: Christchurch
country: New Zealand
facility: Christchurch Clinical Studies Trust
city: Christchurch
country: New Zealand
facility: Southern Clinical Trials - Christchurch
city: Havelock North
country: New Zealand
facility: P3 Research Hawkes Bay
city: Tauranga
country: New Zealand
facility: P3 Research Tauranga
city: Wellington
country: New Zealand
facility: P3 Research Wellington
Study officials:
References: