Phase 1 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics and Pharmacodynamics of Monoclonal Antibody TB31F in Healthy Malaria-naïve Adults in the Netherlands
概览
- 阶段
- 1 期
- 干预措施
- 未指定
- 疾病 / 适应症
- Malaria,Falciparum
- 发起方
- Radboud University Medical Center
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- Number and Severity of Adverse Events After TB31F Administration
- 状态
- 已完成
- 最后更新
- 3年前
概览
简要总结
This phase 1 study aims to assess the safety and tolerability of monoclonal antibody TB31F administered intravenously or subcutaneously at escalating dose levels in healthy, malaria naïve, adults. This study will also evaluate the pharmacokinetics of TB31F and the functional activity of mAb TB31F in the standard membrane feeding assay.
详细描述
This phase 1 study aims to assess the safety and tolerability of monoclonal antibody (mAb) TB31F administered intravenously or subcutaneously in healthy, malaria naïve, adults at the Radboud University Medical Center (Radboudumc). Five groups will receive a single dose of mAb TB31F. Group 1 (n=5) will receive 0.1 mg/kg TB31F, Group 2 (n=5) will receive 1 mg/kg TB31F, group 3 (n=5) will receive 3 mg/kg TB31F, and group 4 (n=5) will receive 10 mg/kg mAb TB31F intravenously. Group 5 will receive 100mg TB31F subcutaneously. Twenty-five (n=25) subjects will be enrolled, as well as 1 reserve subject per group. Safety follow-up will be done at following times: baseline, end of infusion (EOI), 1, 3, 6 and 24 hours and 2, 7, 14, 21, 28, 56 and 84 days after administration. Extra follow-up visits at 4 and 10 days after administration for collection of serum/plasma for pharmacokinetic and pharmacodynamic measurements will be performed in group 5.
研究者
入排标准
入选标准
- •Subject must sign written informed consent to participate in the trial.
- •Subject is able to understand planned study procedures and demonstrate comprehension of the protocol procedures and knowledge of study by passing a quiz (assessment of understanding).
- •In the opinion of the investigator, the subject can and will comply with the requirements of the protocol.
- •Subjects are available to attend all study visits and are reachable by phone throughout the entire study period from day -1 until day 84 (end of study).
- •The subject will remain within reasonable travelling distance from the study center from day -1 until day +7 after mAb TB31F infusion.
- •Subject is a male or non-pregnant and non-lactating female age ≥ 18 and ≤ 35 years and in good health at time of mAb infusion.
- •Subject agrees to their general practitioner (GP) being informed about participation in the study and agrees to sign a form to request the release by their GP, and medical specialist when necessary, of any relevant medical information concerning possible contra-indications for participation in the study to the investigator(s).
- •The subject agrees to refrain from blood donation to Sanquin or for other purposes throughout the study period according to current Sanquin guidelines.
- •Female subjects of non-childbearing potential may be enrolled in the study. Non-childbearing potential is defined as pre-menarche, current bilateral tubal ligation or occlusion, hysterectomy, bilateral ovariectomy or post-menopause. All subjects must agree to use continuous adequate contraception until 2 months after completion of the study. Female subjects must agree not to breastfeed from 30 days prior to mAb infusion until 2 months after completion of the study. Female subject must have a negative pregnancy test at the inclusion visit.
排除标准
- •Acute or chronic disease at time of TB31F administration, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests:
- •Acute disease is defined as the presence of a moderate or severe illness with or without fever. Subjects with a minor illness on the day of TB31F administration will be (temporarily) excluded from participation, but may be re-evaluated for inclusion at a later date. Subjects with a positive SARS-CoV2 test at inclusion will be (temporarily) excluded from participation but may be re-evaluated for inclusion at a later date (following current Radboudumc guidelines).
- •Fever is defined as an oral, axillary or tympanic temperature ≥ 38.0°C (100.4°F). The preferred route for recording temperature in this study will be oral.
- •Any abnormal and clinically significant baseline laboratory screening tests of alanine aminotransferase, aspartate aminotransferase, creatinine, hemoglobin, platelet count or total white blood cell count, as defined in the protocol according to the FDA Toxicity Grading Scale for Healthy Adult and Adolescent Subjects Enrolled in Preventative Vaccine Clinical Trials.
- •History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years.
- •Chronic use of i) immunosuppressive drugs, iii) or other immune modifying drugs within three months prior to study onset (inhaled and topical corticosteroids and oral anti-histamines exempted) or expected use of such during the study period.
- •Positive urine toxicology test for cannabis, cocaine or amphetamines at screening or at inclusion.
- •Screening tests positive for Human Immunodeficiency Virus (HIV), active Hepatitis B Virus (HBV), Hepatitis C Virus (HCV).
- •Use of any investigational or non-registered product (drug or vaccine) during the study period other than the study product.
- •Participation in any other clinical study in the 30 days prior to the start of the study or during the study period.
结局指标
主要结局
Number and Severity of Adverse Events After TB31F Administration
时间窗: Throughout study: solicited local adverse events (day 0 - day 7); solicited general adverse events and clinically significant laboratory abnormalities (day 0 - day 28); unsolicited adverse events (day 0 - day 84), serious adverse events (day 0 - day 84)
* Number and severity of solicited local adverse events of all severities from first product administration through day 7; * Number and severity of solicited general adverse events and clinically significant hematological and biochemical laboratory abnormalities from first product administration through day 28; * Number and severity of unsolicited adverse events from first product administration through end of study; * Occurrence of serious adverse events from first product administration through end of study
次要结局
- Serum Concentration of TB31F(All groups: 6 hours, 24 hours, 48 hours, day 7, day 14, day 21, day 28, day 56, day 84. Groups 1-4 only: end of infusion, 1 hour, 3 hours. Group 5 only: day 4 and day 10.)
- Pharmacodynamics/Functional Transmission-reducing Activity of TB31F(Groups 1 to 4: throughout study until day 84 (baseline, end of infusion, day 7, day 28, day 56, day 84). Group 5: baseline, day 2, day 4, day 7. day 10, day 14, day 28, day 56, day 84.)