Safety and Efficacy of L9LS, a Human Monoclonal Antibody Against Plasmodium Falciparum, in a Randomized, Double-Blind, Placebo-Controlled Trial of Women of Childbearing Potential (WOCBP) in Mali
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 279
- 试验地点
- 6
- 主要终点
- Incidence of local and systemic adverse events (AEs)
研究概览
简要总结
Safety and Efficacy of L9LS, a Human Monoclonal Antibody Against Plasmodium falciparum, in a Randomized, Double-Blind, Placebo-Controlled Trial of Women of Childbearing Potential (WOCBP) in Mali
详细描述
This is a phase 2 trial evaluating the safety and tolerability of a 1-time subcutaneous (SC) administration of L9LS, as well as its protective efficacy against naturally occurring Plasmodium falciparum (Pf) infection over a 6-month malaria season. The primary study hypothesis is that L9LS will be safe and protective against malaria infection. As a secondary objective, the efficacy of L9LS among female participants of childbearing potential within three body weight strata will be compared to placebo. Before study agent administration, all participants will be given artemether-lumefantrine (AL) to clear any preexisting Pf blood stage infection.
This is a randomized, double-blind, placebo-controlled study mainly in WOCBP, weight-stratified (N=270 total), with 2 treatment arms: L9LS 1800 mg SC (n=180) and placebo (n=90) to assess safety and protective efficacy of L9LS. A separate open label male only arm (n=20) will assess sex-differences in the pharmacokinetics (PK) of L9LS at a dose of 1800 mg SC. Male participants will be enrolled during the same time period as the WOCBP arm.
Participants will receive the study agent and be followed at visits on study Days 1, 3, 7, 14, 21, and 28 days later, and once every 2 weeks thereafter through 24 weeks. Primary study assessments include physical examination, blood collection for identification of Pf infection and other research laboratory evaluations.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 49 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Females aged ≥18 and ≤49 years and weighing ≥ 45.0 and ≤ 90.0 kg.
- •Males aged ≥18 and ≤49 years (no weight restrictions).
- •Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process.
- •In good general health and without clinically significant medical history.
- •Able to provide informed consent.
- •Willing to have blood samples and data stored for future research.
- •Resides in or near Kalifabougou, Faladje, or Torodo, Mali, and available for the duration of the study.
- •Females of childbearing potential must be willing to use reliable contraception from 21 days prior to study Day 0 through the final study visit as described below.
- •Reliable methods of birth control include 1 of the following: confirmed pharmacologic contraceptives via parenteral delivery or intrauterine or implantable device.
排除标准
- •Pregnancy, as determined by a positive urine or serum beta-human choriogonadotropin (β hCG) test (if female).
- •Currently breastfeeding.
- •Behavioral, cognitive, or psychiatric disease that in the opinion of the investigator affects the ability of the participant to understand and comply with the study protocol.
- •Study comprehension examination score of <80% correct or per investigator discretion.
- •Hemoglobin, WBC, absolute neutrophil, or platelet count outside the local laboratory-defined limits of normal. (Participants may be included at the investigator's discretion for "not clinically significant" values.)
- •Alanine transaminase (ALT) or creatinine (Cr) level above the local laboratory-defined upper limit of normal. (Participants may be included at the investigator's discretion for "not clinically significant" values.)
- •Infected with HIV, hepatitis C virus (HCV), or hepatitis B virus (HBV).
- •Known or documented sickle cell disease by history. (Note: Known sickle cell trait is NOT exclusionary.)
- •Clinically significant abnormal electrocardiogram (ECG; QTc >460 or other significant abnormal findings, including unexplained tachycardia or bradycardia).
- •Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, endocrine, rheumatologic, autoimmune, hematological, oncologic, or renal disease by history, physical examination, and/or laboratory studies including urinalysis.
- •Receipt of any investigational product within the past 30 days.
- •Participation or planned participation in an interventional trial with an investigational product until the last required protocol visit. [Note: Past, current, or planned participation in observational studies is NOT exclusionary; participation in the placebo arm of the Mali adult CIS43LS MAb trial (ClinicalTrials.gov Identifier: NCT04329104) or the placebo arm of the Mali adult L9LS Mab trial (ClinicalTrials.gov Identifier: NCT05816330) is NOT exclusionary.]
- •Medical, occupational, or family problems as a result of alcohol or illicit drug use during the past 12 months.
- •History of a severe allergic reaction or anaphylaxis.
- •Severe asthma (defined as asthma that is unstable or required emergent care, urgent care, hospitalization, or intubation during the past 2 years, or that has required the use of oral or parenteral corticosteroids at any time during the past 2 years).
- •Pre-existing autoimmune or antibody-mediated diseases including but not limited to: systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, Sjögren's syndrome, or autoimmune thrombocytopenia.
- •Salivary gland disorder diagnosed by a doctor (e.g., parotitis, sialadenitis, sialolithiasis, salivary gland tumors).
- •Known immunodeficiency syndrome.
- •Known asplenia or functional asplenia.
- •Use of chronic (≥14 days) oral or IV corticosteroids (excluding topical or nasal) at immunosuppressive doses (i.e., prednisone >10 mg/day) or immunosuppressive drugs within 30 days of day
- •Receipt of a live vaccine within the past 4 weeks or a killed vaccine within the past 2 weeks prior to study agent administration.
- •Receipt of immunoglobulins and/or blood products within the past 6 months.
- •Previous receipt of an investigational malaria vaccine or MAb in the last 5 years.
- •Known allergies or contraindication against artemether lumefantrine.
- •Other condition(s) that, in the opinion of the investigator, would jeopardize the safety or rights of a participant participating in the trial, interfere with the evaluation of the study objectives, or render the participant unable to comply with the protocol.
研究组 & 干预措施
L9LS in healthy Malian WOCBP
干预措施: Single dose of 1800 mg L9LS SC (Biological)
Placebo in healthy Malian WOCBP
干预措施: Placebo (Other)
L9LS in healthy Malian adult males
干预措施: Single dose of 1800 mg L9LS SC (Biological)
结局指标
主要结局
Incidence of local and systemic adverse events (AEs)
时间窗: Days 0, 1, 3, and 7.
Occurring within 7 days after the administration of study agent
Severity of local and systemic adverse events (AEs)
时间窗: Days 0, 1, 3, and 7.
Occurring within 7 days after the administration of study agent
Number of participants with treatment-related laboratory adverse events
时间窗: Days 7 and 14.
Occurring within 14 days after the administration of study agent
Pf blood-stage infection as detected by microscopic examination of thick blood smear
时间窗: Once every 2 weeks post injection through 24 weeks.
Incidence of laboratory abnormalities
时间窗: Days 7 and 14.
Occurring within 14 days after the administration of study agent
次要结局
- Pf blood-stage infection as detected by thick blood smear and RT-PCR(Blood smear once every 2 weeks post injection through 24 weeks.)
- Concentration of L9LS in sera of recipients.(Through 24 weeks.)