A Phase 1 Study of GTX-B001 in Healthy Subjects and Patients With Chronic Inducible Urticaria

Official title

A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Tolerability, Pharmacokinetic, Pharmacodynamic, and Preliminary Efficacy Trial of GTX-B001 in Healthy Volunteers (Part A) and Patients With Chronic Inducible Urticaria (Part B)

Overview

This is a first-in-human study aimed at determining the safety of a single dose of GTX-B001 in healthy participants and in people with chronic inducible urticaria.

Detailed description

GTX-B001 is a humanized bispecific antibody than binds with one arm to a protein called c-Kit and with the second arm to a protein called CD203c, both expressed on mast cells.

This study is a randomized, double-bind, placebo-controlled phase 1 study evaluating the safety, pharmacokinetics and pharmacodynamics of a single dose of GTX-B001 in healthy participants (Part A) and in patients with chronic inducible urticaria (cold urticaria and symptomatic dermographism) who remain symptomatic despite treatment with antihistamines (Part B). In part B, the preliminary efficacy of GTX-B001 on the signs and symptoms of chronic inducible urticaria will also be evaluated.

48 healthy participants are estimated to be enrolled in part A in five ascending cohorts, while 24 patients with chronic inducible urticaria are estimated to be enrolled in Part B in two ascending cohorts.

Potential participants will be screened for up to 4 weeks prior to enrollment. GTX-B001 will be administered intravenously on Day 1 to randomized participants who will be followed for 12 weeks post-treatment.

Participants will be required to attend a total of 9 visits including the screening visit.

Interventions

• Drug GTX-B001
  Single infusion of one of up to five dosages of GTX-B001
• Drug Normal Saline
  Single infusion of normal saline

Primary outcome measures

• Safety as assessed by the incidence and severity of adverse events (Parts A and B) [Time frame: Day 1 to Day 85]

Secondary outcome measures (1)

• GTX-B001 pharmacokinetics (Parts A and B) [Time frame: Day 1 to Day 85]

Eligibility criteria

Key inclusion Criteria (Part A):

• The subject is between 18 and 55 years of age (both inclusive) at the date of screening.
• The subject is in good general health based on the medical history, physical examination and the results of vital signs, electrocardiogram and clinical laboratory, as judged by the investigator.

Key inclusion Criteria (Part B):

• The subject is between 18 and 75 years of age (both inclusive) at the date of screening
• A history of signs and/or symptoms of ColdU or SD experienced ≥ 3 months prior to screening.
• For ColdU patients, a positive provocation test during screening and baseline, using the TempTest® device.
• For SD patients, a positive provocation test with at least 3 pins during screening and baseline, using the FricTest® device.
• Inadequate control of ColdU or SD by second generation H1-antihistamine (sgAH) as defined as the presence of itch and hives following a trigger (e.g. cold or scratching, respectively) within the last 6 weeks prior to screening in spite of use of a sgAH.
• A Urticaria Control Test (UCT) score of < 12 at screening.

Key exclusion Criteria (Parts A \& B):

• Presence of any clinically significant illness, such as cardiovascular, neurologic, pulmonary, hepatic, renal, metabolic, gastrointestinal, urologic, immunologic, or endocrine disease or disorder that would interfere with the patient's safety or the interpretation of trial results in the judgment of the investigator.
• Treatment with an investigational drug or intervention for any condition within three months of screening, or concurrent participation in another clinical trial in which an investigational drug is administered.
• Treatment with immunomodulating therapy (e.g., intravenous or intramuscular immunoglobulins, systemic corticosteroids, cyclosporine, methotrexate, dapsone, cyclophosphamide, tacrolimus, mycophenolate mofetil, hydroxychloroquine, infliximab, adalimumab, etanercept, etc.) within 4 weeks (or 5 half-lives, whichever is longer) prior to screening.
• Use of any monoclonal antibody or therapeutic protein within 4 weeks (or 5 half-lives, whichever is longer) prior to screening.
• History of anaphylaxis, autoimmune disorders requiring more than topical medication, or asthma requiring regular use of inhaled medication within the past 5 years, unless, in the opinion of the Investigator, the condition is not considered clinically significant and is unlikely to affect subject safety or study outcomes.

Additionally for Part B:

• Disease with symptoms of urticaria or angioedema other than Chronic Urticaria (CU), for example urticaria vasculitis, erythema multiforme, mastocytosis, or drug-induced urticaria. Patients with concomitant Chronic Spontaneous Urticaria (CSU) or other forms of Chronic Inducible Urticaria (CIndU) are eligible provided that symptoms at screening are consistent with ColdU or SD and that ColdU or SD is the dominant form of CU.
• Any other skin disease associated with chronic itching that might influence in the investigators' opinion of the study evaluations and results, e.g., atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, or psoriasis.
• Receipt of any biologic therapy for urticaria control (e.g. omalizumab, dupilumab, ligelizumab, etc.) within three months of screening (whether on-label or off-label).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Sequential

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Germany · 2 centers

• Charité Research Organization gmbh — Berlin
• Fraunhofer Institute For Translational Medicine And Pharmacology — Berlin

Identifiers

NCT: NCT07181369 · GRN-GTXB001-001 · 2025-522126-13-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗