Safety, Tolerability, and Pharmacokinetics of RSV Monoclonal Antibody RSM01 in Healthy Adults

Study Overview
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Brief Summary
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Gates MRI-RSM01-101 is a Phase 1, randomized, double-blind, placebo-controlled, dose-escalation study to evaluate the safety and tolerability, pharmacokinetics, occurrence of ADA, and assessment of neutralizing antibody against RSV after administration of single intravenous or intramuscular doses of RSM01 to healthy adults.

Detailed Description
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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 is 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 is planned at a single study center in the United States. Approximately 56 participants will be enrolled; 48 participants to receive RSM01 and 8 participants to received placebo. Participants will be followed for approximately 5 months (151 days) after dosing.

Official Title
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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

Conditions
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RSV Infection

Intervention / Treatment
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* Drug: RSM01
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant must be 18 to 49 years of age inclusive, at the time of signing the informed consent Participants who are 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 specific 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. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol Participants who agree to stay in contact with the study site for the duration of the study, provide updated contact information as necessary, and have no current plans to relocate from the study area for the duration of the study. Exclusion Criteria: Acute illness and/or body temperature ≥37.5°C or ≥99.5°F on Study Day 1. 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 plan 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. Having received any vaccination (including COVID-19 vaccine) within the 15 days before Day 1,or planning to receive a dose of any vaccine during the 15-day period following Day 1. Receiving or plan 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). Receipt or donation of blood or blood products within 90 days prior to Day 1 or planned receipt or donation during the study period. Receiving or plan 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 having 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; having positive serum pregnancy test during the Screening Phase, planning a pregnancy within 1 year after first dose of study drug. Individuals who are acting as study personnel or immediate family members (brother, sister, child, parent) or the spouse/partner of study personnel.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 49 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, double-blind, placebo-controlled study of RSM01. The study will be conducted in 2 parts: A Dose Escalation Phase (28 participants) with 4 dosing cohorts, followed by an Expansion Phase (28 participants) with a single cohort.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RSM01<br>Participants will be randomized to receive different dose levels of RSM01. Participants will be randomized in a ratio of 6:1 where for every 6 participants receiving active drug (RSM01) 1 participant will receive Placebo. | Drug: RSM01<br>* Cohort 1: RSM01 300 mg IV Cohort 2: RSM01 300 mg IM Cohort 3: RSM01 1000 mg IV Cohort 4: RSM01 3000 mg IV Cohort 5: RSM01 ≥ 300 mg - ≤ 600 mg IM<br>|
| Placebo Comparator: Placebo<br>Participants will receive placebos matched to RSM01. | Other: Placebo<br>* Cohort 1: Placebo IV Cohort 2: Placebo IM Cohort 3: Placebo IV Cohort 4: Placebo IV Cohort 5: Placebo IM<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of unsolicited adverse events (AEs) through Day 151 | To characterize the safety and tolerability of a single dose of RSM01 | 151 days | 
| Number of serious adverse events (SAEs) and AE of special interest (AESIs) through Day 151 | To characterize the safety and tolerability of a single dose of RSM01 | 151 days | 
| Number of Solicited systemic AEs for 7 days after dose administration | To characterize the safety and tolerability of a single dose of RSM01 | 7 days | 
| Solicited local AEs for injection site reactions for 7 days after dose administration (only applies to IM doses) | To characterize the safety and tolerability of a single dose of RSM01 | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of safety laboratory parameters Grade 1 and above through Day 151. | To characterize safety laboratory parameters following RSM01 administration | 151 days | 
| Area under the capillary blood-concentration time curve from zero to infinity (AUC0-∞) | To characterize the pharmacokinetics (PK) following RSM01 administration | 151 days | 
| Day 91 capillary blood-concentration and area under the capillary blood-concentration time curve (CD91 and AUC0-D91) | To characterize the pharmacokinetics (PK) following RSM01 administration | 91 days | 
| Day 151 capillary blood-concentration and area under the capillary blood-concentration time curve (CD151 and AUC0-D151) | To characterize the pharmacokinetics (PK) following RSM01 administration | 151 days | 
| Cmax following IM administration and C0 following IV administration, Cmin | To characterize the pharmacokinetics (PK) following RSM01 administration | 151 days | 
| Tmax and t1/2 | To characterize the pharmacokinetics (PK) following RSM01 administration | 151 days | 
| Systemic Clearance | To characterize the pharmacokinetics (PK) following RSM01 administration | 151 days | 
| Volume of distribution of RSM01 through Day 151 | To characterize the pharmacokinetics (PK) following RSM01 administration | 151 days | 
| To characterize the formation of anti-drug antibodies (ADAs) following RSM01 administration | Incidence of ADAs to RSM01 through Day 151 | 151 days |