Proof of Concept Study of AX-158 in Patients With Mild to Moderate Plaque Psoriasis

NCT05725057 | Completed Phase 1 DMC

• 1 other identifier: AX-158-1011
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 6

Brief Summary

Proof of concept study to assess the safety and tolerability of AX-158 in patients with mild to moderate psoriasis. Patients will be evaluated for a 28-day treatment period with either AX-158 or Placebo and then followed for an additional 30 days for safety.

Conditions

Psoriasis; Plaque Psoriasis

Outcome Measures

Primary Outcomes (1)

• Treatment-Emergent Adverse Events

  The frequency of treatment-emergent adverse events (TEAEs) either started after initial treatment or intensified in severity

  Baseline to 28 days of treatment

Secondary Outcomes (6)

• Psoriasis Area and Severity Index (PASI) -25

  Baseline to 28 days of treatment

• Psoriasis Area and Severity Index (PASI) -50

  Baseline to 28 days of treatment

• Psoriasis Area and Severity Index (PASI) -75

  Baseline to 28 days of treatment

• Psoriasis Area and Severity Index (PASI) - 100

  Baseline to 28 days of treatment

• Biomarkers

  Baseline to 28 days of treatment

Study Arms (2)

AX-158 - (Arm 1)

ACTIVE COMPARATOR

AX-158 Dosage:5 mg capsules Form: Capsule Frequency - 2 capsules daily taken orally Duration - 28 consecutive days

Drug: AX-158

Placebo - (Arm 2)

PLACEBO COMPARATOR

Placebo Dosage: NA Form: Capsule Frequency: 2 capsules daily taken orally Duration: 28 consecutive days

Drug: Placebo

Interventions

AX-158 DRUG

Subjects randomized to this arm will receive AX-158 treatment for 28 days with a 30 day safety follow-up period.

AX-158 - (Arm 1)

Placebo DRUG

Subjects randomized to this arm will receive placebo treatment for 28 days with a 30 day safety follow-up period.

Placebo - (Arm 2)

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Able to understand and willing to provide informed consent and able to comply with the study procedures and restrictions.
• Diagnosis of plaque psoriasis for ≥3 months at time of screening.
• Male or female subjects age 18 to 60 years, inclusive, at the time of informed consent.
• Body mass index (BMI) 18 to 40 kg/m2, inclusive, where BMI (kg/m2) is calculated by body weight (kg)/height2 (m2).
• Female subjects may be enroled if the following criteria are met:
• Documented to be surgically sterile or postmenopausal or practicing true abstinence for at least 28 days prior to investigational product (IP) administration until 30 days (duration of ovulatory cycle) after the last IP administration and having a negative serum pregnancy test at screening and a negative urine pregnancy test within 24 hours prior to the start of IP administration, or
• Women of childbearing potential (WOCBP) must have a negative serum pregnancy test at screening and a negative urine pregnancy test within 24 hours prior to the start of IP administration.
• WOCBP must agree to follow instructions for methods of contraception as described in Appendix 18.2 for the duration of treatment with IP plus 5 half-lives of IP (50 hours) plus 30 days (duration of ovulatory cycle) after the last IP administration.
• Women must not be pregnant, lactating, breastfeeding, or planning pregnancy during the study period.
• Male subjects who are sexually active with WOCBP may be enrolled if they are
• Documented to be surgically sterile (vasectomy), or
• Practicing true abstinence for 90 days after the last IP administration, or
• Males who are sexually active with WOCBP must agree to follow instructions for methods of contraception for the duration of treatment with IP plus 5 half-lives of the IP plus 90 days (duration of sperm turnover) after the last IP administration. In addition, male subjects must be willing to refrain from sperm donation during this time.
• Fully vaccinated for COVID-19 per local regulations and site standard of care (SOC).

You may not qualify if:

• Diagnosis of non-plaque psoriasis (guttate, inverse, pustular, erythrodermic).
• Diagnosis of psoriatic arthritis, uveitis, inflammatory bowel disease, or other immune-mediated conditions that are commonly associated with psoriasis for which a subject requires current systemic (oral, subcutaneous, or intravenous \[IV\]) (including corticosteroids, immunosuppressants, biologics) immunosuppressant medical treatment. Certain therapies such as non-steroidal anti-inflammatory drugs may be permitted at the discretion of the medical monitor.
• Psoriasis affecting the scalp only.
• Inability to tolerate oral medication.
• A clinically significant history of gastrointestinal disorder likely to influence absorption of IP.
• Evidence of renal, hepatic, central nervous system, respiratory, cardiovascular, or metabolic dysfunction.
• Participation in a clinical study and/or receipt of an IP within the previous 3 months or 5 half-lives, whichever is longer, before administration of the first dose of IP.
• History or evidence of active infection and/or febrile illness within 7 days of first administration of IP.
• History of serious bacterial, fungal, or viral infections that required hospitalization and IV antibiotic treatment within 90 days prior to screening, or any recent serious infection requiring antibiotic treatment within 30 days of IP administration.
• Has received a live vaccine within 60 days of first dose of IP.
• Current clinical radiographic or laboratory evidence of active tuberculosis (TB), or any history of or significant risk for TB.
• Any major surgery within 4 weeks of IP administration.
• Has unstable cardiovascular disease, defined as a recent clinical deterioration (eg, unstable angina, rapid atrial fibrillation) in the last 3 months or a cardiac hospitalization within the last 3 months.
• History of malignancy (solid organ or hematologic including myelodysplastic syndrome) or lymphoproliferative disease within the previous 5 years (other than resected cutaneous basal cell or squamous cell carcinoma that has been treated with no evidence of recurrence).
• Has used topical medications/treatments that could affect psoriasis or sPGA evaluation (including, but not limited to, mild to moderate corticosteroids \[eg, hydrocortisone cream, triamcinolone acetonide\], calcineurin inhibitor, calcipotriol, salicylic acid/other keratolytic, coal tar, short contact dithranol) within 4 weeks of the first administration of IP.

Sponsors & Collaborators

• Artax Biopharma Inc: lead

Study Sites (6)

Accellacare Northamptonshire

Corby, United Kingdom

Location

Accellacare Warwickshire

Coventry, United Kingdom

Location

MEU

Manchester, United Kingdom

Location

Accellacare North London

Northwood, United Kingdom

Location

Accellacare South London

Orpington, United Kingdom

Location

Accellacare Yorkshire

Shipley, United Kingdom

Location

Related Publications (9)

• Borroto A, Reyes-Garau D, Jimenez MA, Carrasco E, Moreno B, Martinez-Pasamar S, Cortes JR, Perona A, Abia D, Blanco S, Fuentes M, Arellano I, Lobo J, Heidarieh H, Rueda J, Esteve P, Cibrian D, Martinez-Riano A, Mendoza P, Prieto C, Calleja E, Oeste CL, Orfao A, Fresno M, Sanchez-Madrid F, Alcami A, Bovolenta P, Martin P, Villoslada P, Morreale A, Messeguer A, Alarcon B. First-in-class inhibitor of the T cell receptor for the treatment of autoimmune diseases. Sci Transl Med. 2016 Dec 21;8(370):370ra184. doi: 10.1126/scitranslmed.aaf2140.

  PMID: 28003549 BACKGROUND

• Roy E, Togbe D, Holdorf AD, Trubetskoy D, Nabti S, Kublbeck G, Klevenz A, Kopp-Schneider A, Leithauser F, Moller P, Bladt F, Hammerling G, Arnold B, Pawson T, Tafuri A. Nck adaptors are positive regulators of the size and sensitivity of the T-cell repertoire. Proc Natl Acad Sci U S A. 2010 Aug 31;107(35):15529-34. doi: 10.1073/pnas.1009743107. Epub 2010 Aug 13.

  PMID: 20709959 BACKGROUND

• Roy E, Togbe D, Holdorf A, Trubetskoy D, Nabti S, Kublbeck G, Schmitt S, Kopp-Schneider A, Leithauser F, Moller P, Bladt F, Hammerling GJ, Arnold B, Pawson T, Tafuri A. Fine tuning of the threshold of T cell selection by the Nck adapters. J Immunol. 2010 Dec 15;185(12):7518-26. doi: 10.4049/jimmunol.1000008. Epub 2010 Nov 15.

  PMID: 21078909 BACKGROUND

• Gil D, Schamel WW, Montoya M, Sanchez-Madrid F, Alarcon B. Recruitment of Nck by CD3 epsilon reveals a ligand-induced conformational change essential for T cell receptor signaling and synapse formation. Cell. 2002 Jun 28;109(7):901-12. doi: 10.1016/s0092-8674(02)00799-7.

  PMID: 12110186 BACKGROUND

• Juraske C, Wipa P, Morath A, Hidalgo JV, Hartl FA, Raute K, Oberg HH, Wesch D, Fisch P, Minguet S, Pongcharoen S, Schamel WW. Anti-CD3 Fab Fragments Enhance Tumor Killing by Human gammadelta T Cells Independent of Nck Recruitment to the gammadelta T Cell Antigen Receptor. Front Immunol. 2018 Jul 9;9:1579. doi: 10.3389/fimmu.2018.01579. eCollection 2018.

  PMID: 30038626 BACKGROUND

• Borroto A, Arellano I, Blanco R, Fuentes M, Orfao A, Dopfer EP, Prouza M, Suchanek M, Schamel WW, Alarcon B. Relevance of Nck-CD3 epsilon interaction for T cell activation in vivo. J Immunol. 2014 Mar 1;192(5):2042-53. doi: 10.4049/jimmunol.1203414. Epub 2014 Jan 27.

  PMID: 24470497 BACKGROUND

• Borroto A, Arellano I, Dopfer EP, Prouza M, Suchanek M, Fuentes M, Orfao A, Schamel WW, Alarcon B. Nck recruitment to the TCR required for ZAP70 activation during thymic development. J Immunol. 2013 Feb 1;190(3):1103-12. doi: 10.4049/jimmunol.1202055. Epub 2012 Dec 24.

  PMID: 23267019 BACKGROUND

• Lettau M, Pieper J, Gerneth A, Lengl-Janssen B, Voss M, Linkermann A, Schmidt H, Gelhaus C, Leippe M, Kabelitz D, Janssen O. The adapter protein Nck: role of individual SH3 and SH2 binding modules for protein interactions in T lymphocytes. Protein Sci. 2010 Apr;19(4):658-69. doi: 10.1002/pro.334.

  PMID: 20082308 BACKGROUND

• Yiemwattana I, Ngoenkam J, Paensuwan P, Kriangkrai R, Chuenjitkuntaworn B, Pongcharoen S. Essential role of the adaptor protein Nck1 in Jurkat T cell activation and function. Clin Exp Immunol. 2012 Jan;167(1):99-107. doi: 10.1111/j.1365-2249.2011.04494.x.

  PMID: 22132889 BACKGROUND

MeSH Terms

Conditions

Psoriasis

Condition Hierarchy (Ancestors)

Skin Diseases, Papulosquamous; Skin Diseases; Skin and Connective Tissue Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Prospective, randomized, multicenter, double-blind, placebo-controlled study
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 26, 2023
• First Posted: February 13, 2023
• Study Start: November 30, 2023
• Primary Completion: September 4, 2024
• Study Completion: October 4, 2024
• Last Updated: October 3, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

GB (6)