A Phase 1/2a Single Centre, Randomised, Placebo-controlled, Double-blind, Dose-escalation, Age De-escalation, Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Plasmodium Falciparum Transmission-reducing Activity of Monoclonal Antibody TB31F in Malaria-exposed Malian Adults and Children
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 167
- 试验地点
- 1
- 主要终点
- Occurrence of at least possibly related solicited local and systemic adverse events
研究概览
简要总结
Mali faces a significant challenge with malaria, particularly among its younger population. While existing measures like seasonal chemoprevention and vaccination have shown efficacy, further innovations are necessary to combat this disease. The monoclonal antibody TB31F shows promise in reducing the transmission of malaria. This clinical trial will evaluate the safety and efficacy of the monoclonal antibody TB31F.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Other
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
This is a double-blind randomised controlled trial. The treating physician and staff involved with assessing all laboratory outcomes of the study are blinded. The study pharmacist will be unblinded and responsible for randomisation and treatment preparation. Entomology staff involved in the mosquito feeding assays will be blinded for the parasitology results.
入排标准
- 年龄范围
- 10 Years 至 50 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •SAFETY COHORT (STUDY ARM 1-5)
- •Inclusion Criteria:
- •Written/signed informed consent
- •Adult cohorts: 18-50 years of age
- •School-age children cohorts: 10-15 years of age
- •Haemoglobin ≥10 g/dL
- •Non-lactating females of childbearing potential agree to the use of continuous adequate contraception for 28 days after having received investigational product
- •Subject agrees to refrain from blood donation during the study and for 5 months after having received investigational product
- •Subjects are available to attend all study visits
- •In opinion of the investigator, the subject can and will comply with the requirements of the protocol
排除标准
- •Women who are pregnant (tested at baseline and at day 28 after administration of investigational product by urine and/or serum pregnancy testing (β-hCG)) or lactating
- •Symptomatic malaria
- •Current acute or chronic disease, including clinically significant pulmonary, cardiovascular, hepatic, or renal functional abnormality, as determined by history or physical examination
- •Clinically significant abnormal blood chemistries and haematology
- •History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 year
- •History of adverse reactions to monoclonal antibodies
- •Administration of immunoglobulin and/or blood products within the three months preceding the first dose of the investigational product or planned administration during the study period
- •Any other condition or situation that would, in the opinion of the investigator, place the subject at an unacceptable risk of injury or render the subject unable to meet the requirements of the protocol
- •EFFICACY COHORT (STUDY ARM 6)
- •Inclusion Criteria:
- •Written/signed informed consent
- •10-50 years of age
- •Haemoglobin ≥10 g/dL
- •Non-lactating females of childbearing potential agree to the use of continuous adequate contraception for 28 days after having received investigational product
- •Subject agrees to refrain from blood donation during the study and for 5 months after having received investigational product
- •Subjects are available to attend all study visits
- •In opinion of the investigator, the subject can and will comply with the requirements of the protocol
- •Asymptomatic P. falciparum mono-infection with asexual parasite densities <3000 parasites/µL
- •Presence of P. falciparum gametocytes on thick blood film at a density >16 gametocytes/µL
- •Exclusion Criteria:
- •Women who are pregnant (tested at baseline and at day 28 after administration of investigational product by urine and/or serum pregnancy testing (β-hCG)) or lactating
- •Symptomatic malaria
- •Current acute or chronic disease, including clinically significant pulmonary, cardiovascular, hepatic, or renal functional abnormality, as determined by history or physical examination
- •Clinically significant abnormal blood chemistries and haematology
- •History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years
- •History of adverse reactions to monoclonal antibodies
- •Administration of immunoglobulin and/or blood products within the three months preceding the first dose of the investigational product or planned administration during the study period
- •Any other condition or situation that would, in the opinion of the investigator, place the subject at an unacceptable risk of injury or render the subject unable to meet the requirements of the protocol
- •Use of anti-malarial drug treatment in the last 14 days
- •Prior receipt of an antimalarial monoclonal antibody
- •Prior receipt of a P. falciparum transmission-blocking vaccine
研究组 & 干预措施
2A: control
2 mL normal saline
干预措施: Normal saline (Other)
2B:100 mg TB31F
2 mL (100 mg) TB31F
干预措施: TB31F (Drug)
1A: control
0.2 mL normal saline
干预措施: Normal saline (Other)
1B: 10 mg TB31F
0.2 mL (10 mg) TB31F
干预措施: TB31F (Drug)
3A: control
4 mL normal saline
干预措施: Normal saline (Other)
3B: 200 mg TB31F
4 mL (200 mg) TB31F
干预措施: TB31F (Drug)
4A: control
0.2 mL normal saline
干预措施: Normal saline (Other)
4B: 10 mg TB31F
0.2 mL (10 mg) TB31F
干预措施: TB31F (Drug)
5A: control
2.0 mL normal saline
干预措施: Normal saline (Other)
5B: 100 mg TB31F
2.0 mL (100 mg) TB31F
干预措施: TB31F (Drug)
6A: control
0.6 or 2.0 mL normal saline
干预措施: Normal saline (Other)
6B: 30 mg TB31F
0.6 mL (30 mg) TB31F
干预措施: TB31F (Drug)
6C: 100 mg TB31F
2.0 mL (100 mg) TB31F
干预措施: TB31F (Drug)
结局指标
主要结局
Occurrence of at least possibly related solicited local and systemic adverse events
时间窗: within 7 days of monoclonal antibody TB31F administration
Occurrence of at least possibly related unsolicited adverse events
时间窗: within 28 days of monoclonal antibody TB31F administration
Occurrence of at least possibly related serious adverse events
时间窗: from enrollment to the end of follow-up at 28 or 84 days
Terminal serum half-life (t½) of monoclonal antibody TB31F in serum
时间窗: day 0 [baseline], day 1, day 5, day 7, day 14, day 21, day 28, day 42, day 56, day 84.
Maximum observed serum concentration (Cmax) of monoclonal antibody TB31F in serum
时间窗: day 0 [baseline], day 1, day 5, day 7, day 14, day 21, day 28, day 42, day 56, day 84.
Time to reach maximum serum concentration (tmax) of monoclonal antibody TB31F in serum
时间窗: day 0 [baseline], day 1, day 5, day 7, day 14, day 21, day 28, day 42, day 56, day 84.
Accumulation index (Racc) of monoclonal antibody TB31F in serum
时间窗: day 0 [baseline], day 1, day 5, day 7, day 14, day 21, day 28, day 42, day 56, day 84.
Area under the serum concentration-time curve (AUC0-τ, AUC0-t and AUC) of monoclonal antibody TB31F in serum
时间窗: day 0 [baseline], day 1, day 5, day 7, day 14, day 21, day 28, day 42, day 56, day 84.
Within-group percent reduction in the proportion of mosquitoes infected at day 5 post-treatment compared to baseline (day 0), assessed through direct membrane feeding assays and measured as oocyst prevalence
时间窗: day 0 [baseline] & 5
次要结局
- Within-group percent reduction in the proportion of mosquitoes infected in direct skin feeding assay (DSF), compared within groups between baseline and all feeding time points, and between groups at all feeding timepoints.(day 0 [baseline], 1, and 5)
- Within-group percent reduction in the proportion of mosquitoes infected in direct membrane feeding assays (DMFA), compared within groups between baseline and all feeding time points, and between groups at all feeding timepoints.(day 0 [baseline], 1, 5, and 14)
- Mosquito infection prevalence, assessed by direct skin feed and measured as the proportion dissected mosquitoes with any number of oocysts, compared within groups between baseline and all feeding time points, and between groups at all feeding timepoints.(day 0 [baseline], 1, and 5)
- Mosquito infection prevalence, assessed by DMFA and measured as the proportion dissected with any number of oocysts, compared within groups between baseline and all feeding time points, and between groups at all feeding timepoints.(day 0 [baseline], 1, 5, and 14)
- Mosquito infection intensity, assessed by direct skin feed and measured as the number of oocysts in dissected mosquitoes, compared within groups between baseline and all feeding time points, and between groups at all feeding timepoints.(day 0 [baseline], 1, and 5)
- Mosquito infection intensity, assessed by DMFA and measured as the average number of oocysts in dissected mosquitoes, compared within groups between baseline and all feeding time points, and between groups at all feeding timepoints.(day 0 [baseline], 1, 5, and 14)
- Participant infection prevalence, assessed by DSF as the proportion of individuals infectious to any number of mosquitoes, compared within groups between baseline and all feeding time points, and between groups at all feeding timepoints.(day 0 [baseline], 1, and 5)
- Participant infection prevalence, assessed by DMFA as the proportion of individuals infectious to any number of mosquitoes, compared within groups between baseline and all feeding time points, and between groups at all feeding timepoints.(day 0 [baseline], 1, 5, and 14)
- Transmission-reducing activity in school-age children and adults, measured as the percent reduction in mean oocyst intensity compared to experimental controls, compared within groups and between groups at all feeding timepoints.(day 0 [baseline], 5, 14, 28, 56, and 84)