COVID-19: A Phase I Dose-escalation Study to Evaluate the Safety and Pharmacokinetics of Anti-SARS-CoV-2 Monoclonal Antibody MAD0004J08 in Healthy Adults.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 30
- 试验地点
- 4
- 主要终点
- Severe/serious treatment-emergent adverse events
研究概览
简要总结
A Phase I dose-escalation study to test a new monoclonal antibody (called MAD0004J08) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19 disease. The study aims to evaluate the safety and pharmacokinetics (distribution and elimination) of anti-SARSCoV-2 monoclonal antibody in healthy adults.
The primary objective of the study is to evaluate the safety of anti-SARSCoV-2 monoclonal antibody (that is the appearance of adverse events), the pharmacokinetics (how MAD0004J08 is distributed and eliminated by human body), the generation of anti-drug antibodies (ADAs) (that is the possible production of antibodies against the drug, which could invalidate it efficacy) and finally the ability of MAD0004J08 to neutralize SARSCoV-2. Furthermore a blood sample would be used to evaluate a kit (DIESSE kit), developed by Toscana Life Sciences, able to detect the administered drug. This kit is not used to evaluate study paramethers.
30 subjects, that should respect the Inclusion/Exclusion criteria, will be enrolled.
About 12 visits will be performed during the study, study duration will be about 6 months.
Subjects will be distributed into 3 Cohorts, each of them divided into 2 groups that would receive MAD0004J08 (Dose 1 = 48 mg, Dose 2 = 100 mg or Dose 3 = 400 mg) or placebo. Administration occurs as intramuscular injection (single injection for Cohort 1 and Cohort 2 and, two injections for Cohort 3) .
详细描述
A Phase I dose-escalation study to evaluate the safety and pharmacokinetics of anti-SARSCoV- 2 monoclonal antibody MAD0004J08 in healthy adults.
Two Italian clinical sites are involved in the study. It is a first-in-human, single-dose, dose-escalation, double-blind, placebo-controlled, randomised, safety and pharmacokinetics study.
Three single ascending doses (48 mg, 100 mg and 400 mg) and placebo will be administered by intramuscular injection to three study cohorts (10 subjects/cohort) as single doses, in the morning of day 1.
There are 5 sentinel subjects for each Cohort, they will be treated one at the time at 48 h distance (after evaluation of any possible treatment related adverse event).
Active treatment and placebo will be assigned within each cohort and group according to the study randomisation list.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Identical kits for active and placebo will be provided.
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
- •Informed consent: Signed written informed consent before inclusion in the study
- •Full comprehension: Ability to comprehend the full nature and purpose of the study, including possible risks and side effects; ability to co-operate with the Investigator and to comply with the requirements of the entire study
- •Sex and age: Healthy men and women, 18 - 55 years old, inclusive
- •Negative SARS-CoV-2 serology test at screening (negative anti-S and anti-N)
- •Negative SARS-CoV-2 qRT-PCR in the 72 h before treatment (test on day -3 or -2 or -1 with result before treatment)
- •Body Mass Index: 18.5-30 kg/m2, inclusive, at screening
- •Vital signs: Systolic blood pressure 90-139 mmHg, diastolic blood pressure 60-90 mmHg, heart rate 50-100 bpm, measured after 5 min at rest in the supine position
- •ECG: Electrocardiogram without clinically significant abnormalities at screening
- •Contraception and fertility: Women of child-bearing potential must be using at least one of the following reliable methods of contraception and confirm to use adequate contraception during the study:
- •Hormonal oral or implantable or transdermal, or injectable contraceptives for at least 2 months before the screening visit;
- •A non-hormonal intrauterine device or female condom with spermicide or contraceptive sponge with spermicide or diaphragm with spermicide or cervical cap with spermicide for at least 2 months before the screening visit
- •A male sexual partner who agrees to use a male condom with spermicide
- •A sterile sexual partner
- •A same sex partner Female participants of non-child-bearing potential or in post-menopausal status for at least 1 year will be admitted. For all women, urine pregnancy test result must be negative at screening and day 1
排除标准
- •Physical findings: Clinically significant abnormal physical findings which could interfere with the objectives of the study
- •Allergy: Ascertained or presumptive hypersensitivity to the active principle and/or ingredients of the investigational products; history of anaphylaxis to drugs or allergic reactions likely to be exacerbated by any component of the investigational products in the Investigator's opinion
- •Concomitant medications: Medications, including over the counter (OTC) medications and herbal remedies, for 2 weeks before screening and immunoglobulin or blood products for 6 months before screening (except contraceptives or a single use of paracetamol, aspirin, or combination OTC products containing paracetamol with an antihistamine, or OTC non-steroidal anti-inflammatory drugs (NSAIDs) at a dose equal or lower than that recommended on the package; vitamins and nutritional supplements, if regularly taken before the study, are also allowed)
- •Monoclonal Antibodies (mAb): Previous intake of a mAb within 6 months, or 5 antibody half-life, whichever is longer, before study start
- •Transient acute illness: Acute (time-limited) illness, including fever above 37.5°C on the day before or on the day of the planned treatment; subjects excluded for transient acute illness may be dosed if illness resolves within the screening period or may be rescreened once
- •Diseases: Significant history of renal, hepatic, gastrointestinal, cardiovascular, respiratory, skin, haematological, endocrine, psychiatric or neurological diseases that may interfere with the aim of the study or increase subjects risks; history of malignancy in the last 5 years
- •SARS CoV-2 or COVID-19:
- •Participants with any confirmed current or previous COVID-19 infection at screening, or at day -1 or day 1
- •Participant with clinical signs or symptoms consistent with COVID-19, e.g. fever, dry cough, dyspnoea, sore throat, fatigue or confirmed infection by appropriate laboratory test within the last 4 weeks before/at screening or at day -1 or day 1
- •Any prior intake of investigational or licenced vaccine indicated for the prevention of SARS CoV-2 or COVID-19 or expected intake during follow-up period
- •Has been reported as a case (confirmed or probable) of COVID-19 from the regional health system
- •Immunodeficiency due to illness, including HIV infection (positivity to anti-HIV-Ab), or due to drugs, including any course of glucocorticoid therapy exceeding 2 weeks of prednisone or equivalent within 6 months before screening.
- •Infections: History of active infection with hepatitis B or C or positive test result for anti-HCV-Ab or HBsAg or anti-HBc-Ab at screening; history of infection with SARS or MERS
- •Laboratory analyses: Abnormal laboratory values that in the opinion of the Investigator are clinically significant
- •Investigative drug studies: Participation in the evaluation of any investigational product for 6 months before this study
- •Blood donation: blood donations for 3 months before the study, during the study and in the 3 months after the end of the study
- •Drug test: positive drug test at screening or day -1
- •Drug, alcohol: history of drug or alcohol abuse within 6 months before screening
- •Pregnancy (women only): positive or missing pregnancy test at screening or day 1; pregnant or lactating women
- •Other: Any condition that might compromise study subject's safety or interfere with the study evaluations or interpretation of subject's safety or study results
结局指标
主要结局
Severe/serious treatment-emergent adverse events
时间窗: From Day 1 to Day 8
Proportion of subjects with severe / serious treatment-emergent adverse events (TEAEs) (including clinically relevant laboratory abnormalities, vital signs, and adverse reactions at the injection site) in the 7 days post-treatment.
次要结局
- Unsolicited and solicited TEAE(From Day 1 to Day 180)
- Peak Plasma Concentration (Cmax)(At each visit from Day 1 to Day 180)
- Half-life (t1/2)(At each visit from Day 1 to Day 180)
- Distribution volume (Vz/F)(At each visit from Day 1 to Day 180)
- Number ADA positive subjects(At Day 1, Day 8, Week 2, Month 1, Month 4 and Month 6.)
- Neutralising power analysis(At Day 1,Day 3, Day 8, Month 1, Month 4 and Month 6.)
- Area under the concentration-time curve from time zero to time t (AUC0-t)(At each visit from Day 1 to Day 180)
- Area under the concentration vs. time curve up to infinity (AUC0-∞)(At each visit from Day 1 to Day 180)
- Total body clearance CLt/F(At each visit from Day 1 to Day 180)
- Percentage of ADA positive subjects(At Day 1, Day 8, Week 2, Month 1, Month 4 and Month 6.)
- Time to achieve Cmax (tmax)(At each visit from Day 1 to Day 180)