A Placebo-controlled, Double-blind Phase I Study in Healthy Volunteers With IMP761, a LAG-3 Agonist Antibody
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 79
- 试验地点
- 1
- 主要终点
- Occurrence of clinically relevant abnormalities in vital signs
研究概览
简要总结
The goal of this clinical trial is to evaluate the safety and tolerability of single and multiple doses of IMP761 in healthy female and male volunteers aged 18-55 with no history of disease affecting the immune system or recent use of medication with effects on the immune system.
The main question it aims to answer is:
- if IMP761 is safe and tolerable as determined by assessing vital signs, emerging (serious) adverse events, electrocardiography, and clinical laboratory tests.
Researchers will compare IMP761 to a placebo (a look-alike substance that contains no drug) to see if single and multiple doses of IMP761 are safe and tolerable in healthy volunteers. Part B of the study also investigates the effect of IMP761 on the inhibition of the keyhole limpet haemocyanin (KLH) driven immune response compared with placebo.
Participants will:
- receive IMP761 or a matching placebo intravenously once in single dose (part A and B) and three times in multiple dose (part C) during a 4 day in clinic stay with 4-8 following visits.
- receive KLH challenge
- be monitored for up to 103 days after the first dose.
详细描述
This is a first in human, randomized, prospective, single centre, double blind, placebo-controlled study in healthy volunteers. It consists of three separate parts (Part A, B and C) with different study designs.
The main objective is to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single ascending dose (SAD) (Part A and B) and multiple ascending doses (MAD) (Part C) of IMP761 as assessed by:
- Vital signs
- Treatment-emergent (serious) adverse events ((S)AEs)
- Electrocardiography.
- Clinical laboratory tests
- Laser speckle contrast imaging (LSCI)
- Multispectral skin imaging
Part A: SAD study in healthy subjects (cohort 1, 5 subjects) Cohort 1: 5 subjects, single i.v. dose of IMP761 or placebo (3:2). The first 2 subjects will receive IMP761 or placebo (1:1) as sentinel dosing, while the following 3 subjects will receive IMP761 or placebo (2:1).
Part B: SAD study in healthy subjects, KLH challenge (cohort 2-8, 60 subjects) Cohort 2-3: 5 subjects, single i.v. dose of IMP761or placebo (4:1). Cohort 4-8: 10 subjects, single i.v. dose of IMP761 or placebo (8:2).
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)
盲法说明
Double blind
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Signed informed consent and willing and able to comply with the study protocol;
- •Healthy men or women, 18 to 55 years of age (inclusive) at screening. The health status is verified by absence of evidence of any clinically significant active or uncontrolled chronic disease following a detailed medical history, a complete physical examination including vital signs, laboratory measurements, and 12-lead electrocardiogram (ECG);
- •Female subjects agree to use effective contraception for the duration of their participation in the study and until 186 days after End of Study (EOS).
- •Male volunteers agree to use barrier protection when they engage in sexual relations with women of child-bearing potential (WOCBP) or lactating women for the duration of their participation in the study and until 96 days after EOS.
- •Body mass index (BMI) between 18 and 32 kg/m2, inclusive, and with a minimum bodyweight of 50 kg;
- •Fitzpatrick skin type I-III (cohorts 2-5 only);
- •Has the ability to communicate well with the Investigator in Dutch language and willing to comply with the study restrictions.
- •Has the intention to be reachable by mobile phone or e-mail during the whole study period.
排除标准
- •Evidence of any active or chronic disease or condition that could interfere with, or for which the treatment of might interfere with, the conduct of the study, or that would pose an unacceptable risk to the subject in the opinion of the investigator (following a detailed medical history, physical examination, vital signs (systolic and diastolic blood pressure, pulse rate, body temperature) and 12-lead electrocardiogram (ECG)). Minor deviations from the normal range may be accepted, if judged by the Investigator to have no clinical relevance;
- •Clinically significant abnormalities, as judged by the Investigator, in laboratory test results (including haematology panel, chemistry panel and urinalysis). In the case of uncertain or questionable results, tests performed during screening may be repeated before randomization to confirm eligibility. A rescreen will be allowed based on judgement of the investigator;
- •Positive immunodeficiency virus (HIV1, HIV2) antigen or antibody, Hepatitis B surface antigen (HBsAg), Hepatitis B Virus antibody (HBV Ab), Hepatitis C antibody (HCV Ab), (latent) Tuberculosis at screening;
- •Any disease associated with immune system impairment, including immune mediated diseases, transplantation patients and any confirmed significant allergic reactions (urticaria or anaphylaxis) against any drug or multiple drug allergies (non-active hay fever is acceptable);
- •Use of any medications (prescription or over-the-counter [OTC]), within 21 days prior to dosing with Investigational Medicinal Product (IMP), or less than 5 half-lives (whichever is longer). An exception is made for paracetamol (up to 4 g/day).
- •Use of vitamin, mineral, herbal and dietary supplements within 7 days prior to study drug administration, which are deemed clinically significant by the investigator.
- •Use of immunosuppressive or immunomodulatory medication within 30 days prior to dosing with IMP or planned to use immunosuppressive or immunomodulatory medication during the course of the study.
- •Any vaccination within 30 days prior to dosing with IMP or planned during the course of the study or within 90 days after the last dose of IMP.
- •Use of antibiotic therapy within 90 days prior to dosing with IMP or planned to use during the course of the study.
- •Subject is unable to abstain from travelling to areas with high endemic rates of infectious diseases from study entry until 90 days after the last dose of IMP
- •Alcohol will not be allowed from at least 24 hours before screening and each scheduled visit. At other times during the course of the study no more than 2 units of alcohol per day will be allowed.
- •If a woman, pregnant, or breast-feeding, or planning to become pregnant during the study.
- •Have any current and/or recurrent clinically significant skin condition at the dermal challenge area (i.e. atopic dermatitis), including tattoos.
- •Any known factor, condition, or disease that might interfere with treatment compliance, study conduct or interpretation of the results such as drug or alcohol dependence or psychiatric disease.
研究组 & 干预措施
Single ascending dose IMP761 Part A
Randomized in 3:2 (IMP761:placebo) Cohort 1: 5 subjects
干预措施: IMP761 (Drug)
Single ascending dose Placebo Part A
Randomized in 3:2 (IMP761:placebo) Cohort 1: 5 subjects
干预措施: Placebo (Drug)
Single ascending dose IMP761 Part B KLH challenge
Randomized in 4:1 (IMP761:placebo). KLH immunization followed by IMP761 on Day 1 and dermal rechallenge on day 2 (Cohorts 2-3) or on days 2, 9 and 23 (Cohorts 4-8)
Cohort 2: 5 subjects; Cohort 3: 5 subjects; Cohort 4: 10 subjects; Cohort 5: 10 subjects; Cohort 6: 10 subjects; Cohort 7: 10 subjects; Cohort 8: 10 subjects
干预措施: IMP761 (Drug)
Single ascending dose IMP761 Part B KLH challenge
Randomized in 4:1 (IMP761:placebo). KLH immunization followed by IMP761 on Day 1 and dermal rechallenge on day 2 (Cohorts 2-3) or on days 2, 9 and 23 (Cohorts 4-8)
Cohort 2: 5 subjects; Cohort 3: 5 subjects; Cohort 4: 10 subjects; Cohort 5: 10 subjects; Cohort 6: 10 subjects; Cohort 7: 10 subjects; Cohort 8: 10 subjects
干预措施: keyhole limpet haemocyanin (KLH) (Other)
Single ascending dose Placebo Part B KLH challenge
Randomized in 4:1 (IMP761:placebo). KLH immunization followed by placebo on Day 1 and dermal rechallenge on day 2 (Cohorts 2-3) or on days 2, 9 and 23 (Cohorts 4-8)
Cohort 2: 5 subjects; Cohort 3: 5 subjects; Cohort 4: 10 subjects; Cohort 5: 10 subjects; Cohort 6: 10 subjects; Cohort 7: 10 subjects; Cohort 8: 10 subjects
干预措施: Placebo (Drug)
Single ascending dose Placebo Part B KLH challenge
Randomized in 4:1 (IMP761:placebo). KLH immunization followed by placebo on Day 1 and dermal rechallenge on day 2 (Cohorts 2-3) or on days 2, 9 and 23 (Cohorts 4-8)
Cohort 2: 5 subjects; Cohort 3: 5 subjects; Cohort 4: 10 subjects; Cohort 5: 10 subjects; Cohort 6: 10 subjects; Cohort 7: 10 subjects; Cohort 8: 10 subjects
干预措施: keyhole limpet haemocyanin (KLH) (Other)
Multiple ascending dose IMP761 Part C
Randomized 5:2 (IMP761:placebo) every 28 days, 3 times. MAD Cohort 1: 7 subjects; MAD Cohort 2: 7 subjects
干预措施: IMP761 (Drug)
Multiple dose placebo Part C
Randomized 5:2 (IMP761:placebo) every 28 days, 3 times. MAD Cohort 1: 7 subjects; MAD Cohort 2: 7 subjects
干预措施: Placebo (Drug)
结局指标
主要结局
Occurrence of clinically relevant abnormalities in vital signs
时间窗: From screening to the follow up visit after last treatment (up to 143 days)
Frequency of adverse events (AEs)
时间窗: From administration to the follow up visit after last treatment (up to 103 days)
Duration of adverse events (AEs)
时间窗: From administration to the follow up visit after last treatment (up to 103 days)
Severity of adverse events (AEs)
时间窗: From administration to the follow up visit after last treatment (up to 103 days)
Occurrence of clinically relevant abnormalities in electrocardiography
时间窗: From screening to the follow up visit after last treatment (up to 143 days)
Occurrence of clinically relevant abnormalities in safety laboratory assessments
时间窗: From screening to the follow up visit after last treatment (up to 143 days)
次要结局
- Pharmacokinetic (PK) parameter: Maximum Serum Concentration (Cmax) (Part B and C)(Up to 86 days)
- PK parameter: Timepoint of Maximum Serum Concentration (tmax) (Part B and C)(Up to 86 days)
- PK parameter: Minimum Serum concentration (Cmin) (Part B and C)(Up to 86 days)
- PK parameter: Area Under the Curve (AUC) (Part B and C)(Up to 86 days)
- PK parameter: systemic clearance (CL) (Part B and C)(Up to 86 days)
- PK parameter: Apparent volume of distribution at steady state (Vss) (Part B and C)(Up to 86 days)
- PK parameter: Apparent volume of distribution at terminal state (Vz) (Part B and C)(Up to 86 days)
- PK parameter: elimination half-life (t1/2) (Part B and C)(Up to 86 days)
- PK Parameter: Peak to trough ratio (PTR) (Part C)(Up to 86 days)
- PK Parameter: Trough Concentration (Ctrough ) (Part C)(Up to 86 days)