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

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

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.

Study Overview

• Status: Completed
• Conditions: RSV Infection
• Intervention / Treatment: Other: Placebo; Drug: RSM01

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Orlando, Florida, United States, 32806-1041
      • PPD Phase I Clinic - Orlando

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 49 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Participant must be 18 to 49 years of age (inclusive), at the time of signing the informed consent.
2. Participant is healthy as determined by medical evaluation including medical history, physical examination and laboratory tests.
3. Body mass index (BMI) 18 to 29.9 kg/m2 (inclusive)
4. 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.
5. 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
6. 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.

Exclusion Criteria:

1. 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
2. Evidence and/or history of clinically significant medical condition(s) as judged by the investigator, including malignancies, diabetes mellitus, and unstable or uncontrolled hypertension
3. 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
4. History of anaphylaxis
5. 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
6. 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
7. 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
8. 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)
9. Received or donated blood or blood products within 90 days prior to Day 1 or plans to receive or donate during the study period
10. 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)
11. 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.
12. Concurrent enrollment in another interventional study
13. Previously participated and received study intervention in the current study
14. Female participants: positive serum pregnancy test
15. 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.)
16. Urinalysis abnormality greater than Grade 1 (with the exception of hematuria in a menstruating female), or urinalysis abnormality judged clinically significant by the investigator
17. Clinically significant ECG abnormalities
18. Reactive HIV antibody testing
19. Current hepatitis B and/or hepatitis C infection
20. Positive urine drug screen at screening or Day -1 (with the exception of prescribed drugs)
21. History of allergy or hypersensitivity to the study drug, excipients or related substances
22. 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
23. Acting as study personnel or immediate family members (brother, sister, child, parent) or the spouse/partner of study personnel

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: RSM01; 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 600 mg IM
Placebo Comparator: Placebo; Participants received Placebo matched to RSM01.	Other: Placebo; Cohort 1: Placebo IV Cohort 2: Placebo IM Cohort 3: Placebo IV Cohort 4: Placebo IV Cohort 5: Placebo IM

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Unsolicited Treatment Emergent Adverse Events (TEAEs) 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.	Day 1 through Day 151
Number of Participants With Serious Adverse Events (SAEs) and AE of Special Interest (AESIs) 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.	Day 1 through Day 151
Number of Participants With Solicited Systemic AEs for 7 Days After Dose Administration	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.	Through Day 7
Number of Participants With Solicited Local AEs for Injection Site Reactions for 7 Days After Intramuscular Dose Administration	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	Up to Day 7

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Clinically Significant Hematology Assessments of Grade 1 and Above Through Day 151	Blood samples were collected for the assessment of hemoglobin, platelets, leukocytes, neutrophils and lymphocytes. Laboratory grades were evaluated using the Food and Drug administration (FDA) Toxicity Grading Scale with grading as: Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Life-threatening or disabling. Number of participants with clinically significant hematology assessments of Grade 1 and above has been presented.	Through Day 151
Number of Participants With Clinically Significant Clinical Chemistry Assessments of Grade 1 and Above Through Day 151	Blood samples were collected for the assessment of Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase, Bilirubin, Gamma Glutamyl Transferase, Creatinine, Urea nitrogen, Glucose, Albumin, Sodium and Potassium. Laboratory grades were evaluated using the FDA Toxicity Grading Scale with grading as: Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Life-threatening or disabling. Number of participants with clinically significant clinical chemistry assessments of Grade 1 and above has been presented.	Through Day 151
Area Under the Capillary Blood-concentration Time Curve From Zero to Infinity (AUC 0-infinity) After Administration of RSM01	Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of RSM01. PK parameters were analyzed using standard non-compartmental analysis. AUC(0-infinity) in participants with AUC extrapolation exceeding 20% was deemed unreliable in the terminal phase and thus omitted from the summary statistics.	Day 151
Day 91 Capillary Blood-concentration (CD91) After Administration of RSM01	Blood samples were collected at indicated time points for PK analysis of RSM01. PK parameters were analyzed using standard non-compartmental analysis.	Day 91
Day 91 Area Under the Capillary Blood-concentration Time Curve (AUC 0-D91) After Administration of RSM01	Blood samples were collected at indicated time points for PK analysis of RSM01. PK parameters were analyzed using standard non-compartmental analysis.	Day 91
Day 151 Capillary Blood-concentration (CD151) After Administration of RSM01	Blood samples were collected at indicated time points for PK analysis of RSM01. PK parameters were analyzed using standard non-compartmental analysis.	Day 151
Day 151 Area Under the Capillary Blood-concentration Time Curve (AUC 0-D151) After Administration of RSM01	Blood samples were collected at indicated time points for PK analysis of RSM01. PK parameters were analyzed using standard non-compartmental analysis.	Day 151
Maximum Capillary Blood Concentration (Cmax) After Administration of RSM01	Blood samples were collected at indicated time points for PK analysis of RSM01. PK parameters were analyzed using standard non-compartmental analysis.	Day 151
Minimum Capillary Blood Concentration (Cmin) After Administration of RSM01	Blood samples were collected at indicated time points for PK analysis of RSM01. PK parameters were analyzed using standard non-compartmental analysis.	Day 151
Time to Maximum Capillary Blood-concentration (Tmax) After Administration of RSM01	Blood samples were collected at indicated time points for PK analysis of RSM01. PK parameters were analyzed using standard non-compartmental analysis.	Day 151
Apparent Terminal Half-Life After Administration of RSM01	Blood samples were collected at indicated time points for PK analysis of RSM01. PK parameters were analyzed using standard non-compartmental analysis. Apparent terminal half-life in participants with AUC extrapolation exceeding 20% was deemed unreliable in the terminal phase and thus omitted from the summary statistics.	Day 151
Total Body Clearance (CL) After Intravenous Dose Administration of RSM01	Blood samples were collected at indicated time points for PK analysis of RSM01. PK parameters were analyzed using standard non-compartmental analysis. CL post intravenous administration in participants with AUC extrapolation exceeding 20% was deemed unreliable in the terminal phase and thus omitted from the summary statistics.	Day 151
Apparent Total Body Clearance (CL) After Intramuscular Dose Administration of RSM01	Blood samples were collected at indicated time points for PK analysis of RSM01. PK parameters were analyzed using standard non-compartmental analysis. Total body CL post intramuscular administration in participants with AUC extrapolation exceeding 20% was deemed unreliable in the terminal phase and thus omitted from the summary statistics.	Day 151
Volume of Distribution (Vz) After Intravenous Dose Administration of RSM01	Blood samples were collected at indicated time points for PK analysis of RSM01. PK parameters were analyzed using standard non-compartmental analysis. Vz post intravenous administration in participants with AUC extrapolation exceeding 20% was deemed unreliable in the terminal phase and thus omitted from the summary statistics.	Day 151
Apparent Volume of Distribution (Vz) After Intramuscular Dose Administration of RSM01	Blood samples were collected at indicated time points for PK analysis of RSM01. PK parameters were analyzed using standard non-compartmental analysis. Vz post intramuscular administration in participants with AUC extrapolation exceeding 20% was deemed unreliable in the terminal phase and thus omitted from the summary statistics.	Day 151
Number of Participants With Positive Anti-drug Antibodies (ADAs) at Baseline and Post-Baseline Through Day 151 Following RSM01 Administration	Whole blood samples in serum separator tubes and volumetric absorptive microsampling (VAMS) samples were collected for detection of ADAs against RSM01 in serum and capillary blood, respectively. The detection of ADA to RSM01 was performed using a validated immunoassay method with tiered testing of screening, confirmatory, and titration. Number of participants with positive ADAs at Baseline and post-Baseline through Day 151 following RSM01 administration has been presented.	Baseline (Day 1) and post-Baseline through Day 151

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
To characterize RSV neutralizing antibody activity following RSM01 administration	Determination of RSV neutralizing antibody levels through Day 151	151 days

Collaborators and Investigators

• Sponsor: Bill & Melinda Gates Medical Research Institute
• Collaborators: PPD Phase I Clinic - Orlando
• Investigators: Study Director: Gates MRI, Bill & Melinda Gates Medical Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): November 16, 2021
• Primary Completion (Actual): August 23, 2022
• Study Completion (Actual): December 7, 2022

Study Registration Dates

• First Submitted: October 6, 2021
• First Submitted That Met QC Criteria: November 11, 2021
• First Posted (Actual): November 12, 2021

Study Record Updates

• Last Update Posted (Actual): May 20, 2024
• Last Update Submitted That Met QC Criteria: December 1, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Monoclonal antibody
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Paramyxoviridae Infections; Mononegavirales Infections; Pneumovirus Infections; Respiratory Syncytial Virus Infections
• Other Study ID Numbers: Gates MRI-RSM01-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymized or deidentified, as appropriate, participant level data may be shared with external researchers in accordance with the trial participants' written and executed informed consent document and any local or applicable regulations on data sharing. Qualified researchers may submit a request for anonymized or de-identified participant level data along with a research proposal to Gates MRI for review. A data sharing agreement must be in place before any clinical trial data are shared. There are additional circumstances that may prevent the sharing of data with external researchers, including but not limited to contractual obligations to existing partners and any restrictions imposed by regulatory bodies.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No