NCT05318534招募中1 期
GL-0719 - A Phase 1, Double-blind, Placebo-controlled, Single Ascending Intravenous and Subcutaneous Injection Dose, Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Study in Healthy Male and Female Subjects and an Open-label Evaluation of Safety, Tolerability, Pharmacokinetics, and Pilot Efficacy Biomarkers in Subjects With Cold Agglutinin Disease
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- Gliknik Inc.
- 入组人数
- 70
- 试验地点
- 2
- 主要终点
- Incidence of abnormal clinical laboratory findings in 12-lead ECG parameters, vital signs, physical examination and measurement of cytokines
研究概览
简要总结
The purpose of this first-in-human (FIH) study is to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of GL-0719 following single intravenous (IV) and subcutaneous injection (SC) doses in healthy adult male and female subjects.
In addition, safety, tolerability, PK, and pilot efficacy biomarkers will be evaluated in subjects with cold agglutinin disease (CAD).
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •for Cohorts 1 to 7
- •Healthy female or male subjects who, at the time of screening, are between the ages of 18 and 65 years, inclusive.
- •Females will not be pregnant or lactating, and females of childbearing potential and males will agree to use contraception.
- •Body mass index of 18.0 to 32.0 kg/m^2, inclusive; and a total body weight > 50 kg up to a maximum of 110 kg.
- •Study subjects must have received a quadrivalent meningococcal conjugate vaccine (meningococcal serogroups A, C, W, and Y) within the past 5 years or vaccination a minimum of 14 days prior to initial study drug administration.
- •The subject must be capable of understanding the investigational nature, potential risks and benefits of the study and capable of providing valid informed consent.
- •Inclusion Criteria for Cohorts 8 to 9
- •Female or male subjects who, at the time of screening, are at least 18 years of age with a total body weight of ≥ 50 kg.
- •Females will not be pregnant or lactating, and females of childbearing potential and males will agree to use contraception.
- •The subject must be capable of understanding the investigational nature, potential risks and benefits of the study and capable of providing valid informed consent.
- •The subject must be willing to return to the study center for study treatment and study-related follow-up procedures as required by the protocol.
- •Study subjects must have received a quadrivalent meningococcal conjugate vaccine (meningococcal serogroups A, C, W, and Y) within the past 5 years or vaccination a minimum of 14 days prior to initial study drug administration.
- •The Participant Identification Center (PIC) site will have provided evidence that the PIC site used to confirm diagnosis of Cold Agglutinin Disease (CAD)
- •Primary Cold Agglutinin Disease (CAD) or CAD secondary to active lymphoid or other hematologic malignancy (Cold Agglutinin Syndrome).
- •Hemoglobin level < 105 gram per liter (g/L).
- •Bilirubin level above the normal reference range.
排除标准
- •for Cohorts 1 to 7
- •History of any clinically significant (as determined by the investigator) cardiac, endocrine, hematological, hepatic, immunological, metabolic, urological, pulmonary, neurological, dermatological, psychiatric, renal, or other major disease.
- •Evidence of clinically significant medical condition or other condition that might significantly interfere with the absorption, distribution, metabolism, or excretion of study drug, or place the subject at an unacceptable risk as a participant in this study.
- •Signs and symptoms of, or diagnosis consistent with a chronic autoimmune disorder and/or positive antinuclear antibodies (ANA) test by indirect immunofluorescence confirmed by ANA titer ≥ 1:
- •Documented history of autoimmune disease, or history of a syndrome that required systemic steroids or immunosuppressive medications, except for subjects with vitiligo or resolved childhood asthma/atopy.
- •Any underlying medical condition that, in the opinion of the investigator, renders the subject a poor candidate for this study or could confound the results of the study or put the subject at undue risk.
- •Key Exclusion Criteria for Cohorts 8 to 9
- •CAD secondary to infection or an autoimmune disorder.
- •CAD secondary to active lymphoid or other hematologic malignancy not meeting the inclusion criteria.
- •Diagnosis of any other malignancy except for adequately treated basal or squamous cell skin cancer, curatively treated in situ disease, or other cancer from which the subject has been disease-free for ≥ 5 years.
- •Clinically relevant infection of any kind within the month preceding enrollment (example, active hepatitis C, pneumonia).
- •Clinical diagnosis of Systemic Lupus Erythematosus (SLE), other autoimmune disorders, or ANA titer > 1:160 at Screening.
- •Positive hepatitis panel and/or positive HIV (Human Immuno Deficiency) test. Subjects whose results are compatible with prior immunization may be included at the discretion of the investigator.
- •Positive HIV antibody at Screening.
- •Treatment with an investigational drug within 90 days or five half-lives preceding the first dose of IP (whichever is longer), with the exception of subjects who received GL-0719 in this study in Cohort 8, who cannot be re-enrolled in Cohort 9 within 60 days after their last dose of GL-
- •Concurrent plasma exchange therapy.
- •Other protocol defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
GL-0719
Experimental
Dose level cohorts randomized in a 3:1 ratio to GL-0719 or placebo treatment, respectively.
The study will comprise a single-dose, sequential-group design.
Single Ascending IV Dose Cohorts
- Cohort 1: 4 subjects
- Cohort 2: 8 subjects
- Cohort 3: 8 subjects
- Cohort 4: 8 subjects
- Cohort 5: 8 subjects
Subcutaneous Injection Cohort
- Cohort 6: 8 subjects
- Cohort 7: 8 subjects
- Cohort 8 (Patient Arm): Up to 6 subjects with Cold Agglutinin Disease (CAD); Placebo is not applicable.
- Cohort 9 (Patient Arm): Up to 12 subjects with Cold Agglutinin Disease (CAD); Placebo is not applicable.
干预措施: GL-0719 (Drug)
Placebo
Placebo Comparator
Dose level cohorts randomized in a 3:1 ratio to GL-0719 or placebo treatment, respectively.
The study will comprise a single-dose, sequential-group design.
Single Ascending IV Dose Cohorts
- Cohort 1: 4 subjects
- Cohort 2: 8 subjects
- Cohort 3: 8 subjects
- Cohort 4: 8 subjects
- Cohort 5: 8 subjects
Subcutaneous Injection Cohort
- Cohort 6: 8 subjects
- Cohort 7: 8 subjects
干预措施: Placebo (Drug)
结局指标
主要结局
Incidence of abnormal clinical laboratory findings in 12-lead ECG parameters, vital signs, physical examination and measurement of cytokines
时间窗: Screening (Days -42 to -15) to Follow-up (Day 31±2)
Incidence and severity of adverse events (AEs)
时间窗: Day 1 to Follow-up (Day 31±2)
Incidence of laboratory abnormalities, based on hematology, clinical chemistry, and urinalysis test results
时间窗: Screening (Days -42 to -15) to Follow-up (Day 31±2)
次要结局
- Time of the maximum observed concentration (tmax)(Day 1 to Follow-up (Day 31±2))
- Maximum Observed Concentration (Cmax)(Day 1 to Follow-up (Day 31±2))
- Apparent terminal elimination half-life (t1/2)(Day 1 to Follow-up (Day 31±2))
- Incidence of anti-drug antibodies(Day -1, Day 15±1 and Follow-up (Day 31±2))
- Area Under the Concentration time Curve from Time 0 Extrapolated to Infinity (AUC0-∞)(Day 1 to Follow-up (Day 31±2))
- Area Under the Concentration time Curve from Time 0 to the Time of the Last (AUC0-tlast)(Day 1 to Follow-up (Day 31±2))
- The degree of complement classical pathway inhibition in study subjects over time(Day 1 to Follow-up (Day 31±2))
研究者
研究点 (2)
Loading locations...
相似试验
已完成
1 期
A Dose Escalating Study of HC002 in Healthy Adult VolunteersInflammatory DiseaseAutoimmune DiseasesNCT06670274Holoclara Aus Pty Ltd56
终止
1 期
A Study to Assess the Safety and Tolerability of Single and Multiple Doses of AZD4831 in Healthy Male SubjectsCardiovascular DiseaseNCT02712372AstraZeneca104
已完成
1 期
A Study to Assess the Safety and Tolerability of Single Doses of AZD4076 in Healthy Male SubjectsNon-alcoholic Steatohepatitis (NASH)NCT02612662AstraZeneca40
已完成
1 期
A First In Human Study To Evaluate The Safety, Tolerability And Pharmacokinetics Of PF-04455242 In Single Rising Doses In Healthy Adult VolunteersBipolar DepressionNCT00938301Pfizer18
已完成
1 期
A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Ir-CPI in Healthy Male SubjectsHealthyNCT04653766Bioxodes S.A.32