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)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 72
- 试验地点
- 5
- 主要终点
- Safety as assessed by the incidence and severity of adverse events (Parts A and B)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •(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).
研究组 & 干预措施
Part A (HV) - Normal Saline
Healthy participants assigned to receive placebo will receive a single dose of normal saline
干预措施: Normal Saline (Drug)
Part A (HV) - GTX-B001
Healthy participants will receive a single dose of GTX-B001
干预措施: GTX-B001 (Drug)
Part B (ColdU/SD) - GTX-B001
Patients with cold urticaria or symptomatic dermographism will receive a single dose of GTX-B001
干预措施: GTX-B001 (Drug)
Part B (ColdU/SD) - Normal Saline
Patients with cold urticaria or symptomatic dermographism assigned to receive placebo will receive a single dose of normal saline
干预措施: Normal Saline (Drug)
结局指标
主要结局
Safety as assessed by the incidence and severity of adverse events (Parts A and B)
时间窗: Day 1 to Day 85
Safety and tolerability of a single intravenous infusion of GTX-B001 as assessed by the percentage of subjects at each dose level with Grade 2 or higher adverse events as assessed by the Common Terminology Criteria for Adverse Events (CTCAE).
次要结局
- GTX-B001 pharmacokinetics (Parts A and B)(Day 1 to Day 85)
- GTX-B001 pharmacokinetics (Parts A and B)(Day 1 to Day 85)