Evidence map›Paper›PMID 37668898›Full record

ArticleDermatology and therapy2023

Safety, Pharmacokinetics and Preliminary Efficacy of IL4-Rα 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.

Christopher John Wynne, Alexandra Cole, Charlotte Lemech, Guoqin Wang, Yu Zhang, Benchao Chen, Max Wang, Baiyong Li, Michelle Xia, Rodney Sinclair

Registry-linked trialOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Dermatology and therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04256174 (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), which is not on this map. Cited by 9 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 2 pooled it
3.1field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04256174 phase1completednot on this map

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

TypeinterventionalSponsorAkesobio Australia Pty LtdRan2020 to 2021Enrolled80ConditionsAtopic DermatitisArmsAK120 or placebo- Part 1- Cohort 1, AK120 or placebo- Part 1- Cohort 2, AK120 or placebo- Part 1- Cohort 3, AK120 or placebo- Part 1- Cohort 4, AK120 or placebo- Part 1- Cohort 5
3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 2 syntheses or guidelines pooled it, 11 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Review
  4. Article
  5. Article
  6. Review
  7. Review
  8. Review
  9. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 2 countries.

Christopher John WynneChristchurch Clinical Studies Trust, 4/264 Antigua Street, Christchurch, 8011, New Zealand.
Alexandra ColeChristchurch Clinical Studies Trust, 4/264 Antigua Street, Christchurch, 8011, New Zealand.
Charlotte LemechScientia Clinical Research Ltd, The Bright Building, Level 5, Corner High and Avoca Street, Randwick, NSW, 2031, Australia.
Guoqin WangAkeso Biopharma, Inc., Zhongshan, China.
Yu ZhangAkeso Biopharma, Inc., Zhongshan, China.
Benchao ChenAkeso Biopharma, Inc., Zhongshan, China.
Max WangAkeso Biopharma, Inc., Zhongshan, China.
Baiyong LiAkeso Biopharma, Inc., Zhongshan, China.
Michelle XiaAkeso Biopharma, Inc., Zhongshan, China.
Rodney SinclairSinclair Dermatology, 2 Wellington Parade, East Melbourne, VIC, 3002, Australia. Rodney.Sinclair@sinclairdermatology.com.au.
Christchurch Clinical Studies Trust · NZSinclair Dermatology · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionInterleukin-4 (IL-4) and interleukin-13 (IL-13) are two essential cytokines involved in the T helper 2 (Th2)-mediated inflammatory response to diseases, such as atopic dermatitis (AD). AK120 is a humanized immunoglobulin G subclass 4 (IgG4) monoclonal antibody (mAb) directed against the IL-4 receptor alpha (IL-4Rα) subunit shared by the IL-4 and IL-13 receptor complexes. This mAb inhibits the signaling of the IL-4 and IL-13 cytokines.

methodsThe study consisted of two parts. Part 1 was a single ascending dose (SAD) study with five cohorts (receiving 15, 50, 150, 300 or 600 mg of AK120, respectively) of healthy subjects; part 2 was a multiple ascending dose (MAD) study with four cohorts (receiving AK120 at doses of 300 mg once every 2 weeks [Q2W], 300 mg once weekly [QW], 150 mg QW or 75 mg QW) of subjects with AD. A total of 81 subjects (40 in part 1, 41 in part 2) were enrolled in the study.

resultsThe compound was safe and well tolerated in both a SAD up to 600 mg in healthy subjects and in a MAD from 75 to 600 mg in subjects with AD. The exposure of AK120 increased in an approximately dose-dependent manner upon subcutaneous dosing. The levels of the biomarkers serum thymus and activation-regulated chemokine ligand 17 (TARC/CCL17) and immunoglobulin E decreased from baseline after AK120 administration, indicating the inhibition of the IL-4/IL-13 signaling pathways. AK120 showed improved Eczema Area and Severity Index (EASI) scores, and the proportion of subjects with Investigator Global Assessment (IGA) score 0/1 increased after AK120 treatment.

conclusionsAK120 exhibited an acceptable safety profile in healthy and AD subjects, and showed preliminary efficacy. These findings support the continued investigation of AK120 for treating AD. CLINICAL

trial registrationClinicalTrials.gov identification number: NCT04256174.

Indexed as

Atopic dermatitisClinical studyFirst-in-humanInterleukin-13Interleukin-4Monoclonal antibody

Identifiers

PMID37668898
PMCPMC10539271
OpenAlexW4386439076

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.