A Phase 1 Randomized, Double-blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single Ascending Doses of RSM01, a Monoclonal Antibody Targeting Respiratory Syncytial Virus, in Healthy Adults
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 56
- 试验地点
- 1
- 主要终点
- Number of Participants With Solicited Local AEs for Injection Site Reactions for 7 Days After Intramuscular Dose Administration
研究概览
简要总结
Gates MRI-RSM01-101 was a Phase 1, randomized, double-blind, placebo-controlled, dose-escalation study to evaluate the safety and tolerability, pharmacokinetics, occurrence of Anti-drug antibody (ADA), and assessment of neutralizing antibody against RSV after administration of single intravenous or intramuscular doses of RSM01 to healthy adults.
详细描述
Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection (LRTI) among infants and young children, resulting in annual epidemics worldwide.
RSM01, a monoclonal antibody targeting RSV, may potentially provide an effective method to protect infants from RSV disease based on its potency and an extended half-life that is expected to support once-per-RSV-season administration.
This study was a first-in-human evaluation of RSM01 in healthy male and female adults with the goal of characterizing the safety and tolerability of a range of single doses of RSM01 to enable determination of appropriate dose(s) to be administered to infants in a future study. Enrollment was planned at a single study center in the United States. 56 participants were enrolled; 48 participants received RSM01 and 8 participants received Placebo. Participants were followed for approximately 5 months (151 days) after dosing.
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
- Double (Participant, Investigator)
盲法说明
Participants and all study personnel were blinded to the randomization. Authorized study site personnel would administer doses.
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
- •Participant must be 18 to 49 years of age (inclusive), at the time of signing the informed consent.
- •Participant is healthy as determined by medical evaluation including medical history, physical examination and laboratory tests.
- •Body mass index (BMI) 18 to 29.9 kg/m2 (inclusive)
- •Both males and females are eligible to participate. Female participants must not be pregnant, breastfeeding, or attempting to become pregnant for 28 days prior to screening and throughout the duration of the study. Females must be willing to comply with protocol-specified contraception for the duration of their participation in the study and for 90 days following the completion of the study. Male participants with partners of childbearing potential must be willing to comply with protocol specific contraception for the duration of their participation in the study and for 90 days following the completion of the study. Males must also agree to refrain from sperm donation for at least 90 days after they complete the study.
- •Participant must be capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol
- •Participant agrees to stay in contact with the study site for the duration of the study, provide updated contact information as necessary, and has no current plans to relocate from the study area for the duration of the study.
排除标准
- •Acute illness and/or body temperature ≥37.5°C or ≥99.5°F on Study Day
- •NOTE: This is a temporary exclusion for which the participant may be re-evaluated
- •Evidence and/or history of clinically significant medical condition(s) as judged by the investigator, including malignancies, diabetes mellitus, and unstable or uncontrolled hypertension
- •History of any autoimmune disease or immune deficiency or other impairment to the immune system, including but not limited to HIV, autoimmune conditions, or immunosuppressive therapy. Note: history of Hashimoto's thyroiditis is not an exclusion criterion
- •History of anaphylaxis
- •Any current medical, psychiatric, occupational, or substance abuse problems that, in the opinion of the investigator, will make it unlikely that the participant will comply with the protocol
- •Receiving or plans to receive any medications or other therapies that may impact the immune system such as allergy injections, interferon, immunomodulators, cytotoxic drugs or other drugs known to be frequently associated with major organ toxicity within 90 days prior to Day 1
- •Received any vaccination (including COVID-19 vaccine) within the 15 days before Day 1 or plans to receive a dose of any vaccine during the 15-day period following Day 1
- •Receiving or plans to receive immunosuppressive agents including systemic steroids within 90 days prior to Day 1 (individuals using inhaled or topical corticosteroids, prednisone (or equivalent) dose of ≤ 20 mg/day for ≤ 14 days, and intra-articular corticosteroids are permitted)
- •Received or donated blood or blood products within 90 days prior to Day 1 or plans to receive or donate during the study period
- •Received or plans to receive antibody or biologic therapy within 180 days prior to Day 1 or any time during the study period, whether licensed or investigational (e.g., immunoglobulin products, monoclonal antibodies, or antibody fragments)
- •Participation in an interventional clinical trial and/or receipt of any investigational drug within 30 days or 5 half-lives of the investigational drug before the first day of study drug dosing in this study, whichever is longer.
- •Concurrent enrollment in another interventional study
- •Previously participated and received study intervention in the current study
- •Female participants: positive serum pregnancy test
- •Safety laboratory values outside of normal range, for age and sex that are suggestive of a disease state (Grade 1 abnormalities will not lead to exclusion if the investigator considers them not clinically significant.)
- •Urinalysis abnormality greater than Grade 1 (with the exception of hematuria in a menstruating female), or urinalysis abnormality judged clinically significant by the investigator
- •Clinically significant ECG abnormalities
- •Reactive HIV antibody testing
- •Current hepatitis B and/or hepatitis C infection
- •Positive urine drug screen at screening or Day -1 (with the exception of prescribed drugs)
- •History of allergy or hypersensitivity to the study drug, excipients or related substances
- •Female participants with any one of the following conditions: currently pregnant or lactating/nursing; has positive serum pregnancy test during the Screening Phase, planning a pregnancy within 1 year after first dose of study drug
- •Acting as study personnel or immediate family members (brother, sister, child, parent) or the spouse/partner of study personnel
研究组 & 干预措施
RSM01
Participants were randomized to receive different dose levels of RSM01. Participants were randomized in a ratio of 6:1 where for every 6 participants received active drug (RSM01), 1 participant received Placebo.
干预措施: RSM01 (Drug)
Placebo
Participants received Placebo matched to RSM01.
干预措施: Placebo (Other)
结局指标
主要结局
Number of Participants With Solicited Local AEs for Injection Site Reactions for 7 Days After Intramuscular Dose Administration
时间窗: Up to Day 7
Solicited local AEs were defined events that participants were specifically asked about and which were noted by participants in the diary card. Solicited local AEs for injection site reactions included AEs include pain, redness and swelling. Number of participants with solicited local AEs for injection site reactions for 7 days after intramuscular dose administration has been presented
Number of Participants With Unsolicited Treatment Emergent Adverse Events (TEAEs) Through Day 151
时间窗: Day 1 through Day 151
A TEAE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. A memory aid was utilized by participants to collect unsolicited TEAEs beginning at discharge from the clinic, through Day 151. Participants were instructed to record unsolicited TEAEs whenever they occurred, recording such TEAEs on the memory aid. The memory aids were collected and reviewed by site staff at each subsequent visit through the end of the study. Number of participants with unsolicited TEAEs through Day 151 has been presented.
Number of Participants With Serious Adverse Events (SAEs) and AE of Special Interest (AESIs) Through Day 151
时间窗: Day 1 through Day 151
An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgment. AESIs were defined as events of potential immunologic etiology, including immune-related AEs (irAEs). Number of participants with SAEs and AESIs through Day 151 has been presented.
Number of Participants With Solicited Systemic AEs for 7 Days After Dose Administration
时间窗: Through Day 7
Solicited systemic AEs were defined events that participants were specifically asked about and which were noted by participants in the diary card. Systemic solicited AEs included fever, headache, tiredness, joint pain, muscle pain, nausea, vomiting and diarrhea. Number of participants with solicited systemic AEs for 7 days after dose administration has been presented.
次要结局
- Total Body Clearance (CL) After Intravenous Dose Administration of RSM01(Day 151)
- Apparent Volume of Distribution (Vz) After Intramuscular Dose Administration of RSM01(Day 151)
- Number of Participants With Clinically Significant Hematology Assessments of Grade 1 and Above Through Day 151(Through Day 151)
- Day 151 Area Under the Capillary Blood-concentration Time Curve (AUC 0-D151) After Administration of RSM01(Day 151)
- Apparent Terminal Half-Life After Administration of RSM01(Day 151)
- Apparent Total Body Clearance (CL) After Intramuscular Dose Administration of RSM01(Day 151)
- Day 91 Area Under the Capillary Blood-concentration Time Curve (AUC 0-D91) After Administration of RSM01(Day 91)
- Day 151 Capillary Blood-concentration (CD151) After Administration of RSM01(Day 151)
- Maximum Capillary Blood Concentration (Cmax) After Administration of RSM01(Day 151)
- Minimum Capillary Blood Concentration (Cmin) After Administration of RSM01(Day 151)
- Time to Maximum Capillary Blood-concentration (Tmax) After Administration of RSM01(Day 151)
- Volume of Distribution (Vz) After Intravenous Dose Administration of RSM01(Day 151)
- Number of Participants With Clinically Significant Clinical Chemistry Assessments of Grade 1 and Above Through Day 151(Through Day 151)
- Area Under the Capillary Blood-concentration Time Curve From Zero to Infinity (AUC 0-infinity) After Administration of RSM01(Day 151)
- Day 91 Capillary Blood-concentration (CD91) After Administration of RSM01(Day 91)
- Number of Participants With Positive Anti-drug Antibodies (ADAs) at Baseline and Post-Baseline Through Day 151 Following RSM01 Administration(Baseline (Day 1) and post-Baseline through Day 151)