Clinical trial NCT05118386: Safety, Tolerability, and Pharmacokinetics of RSV Monoclonal Antibody RSM01 in Healthy Adults
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: RSV Infection
Keywords: Monoclonal antibody
Lead sponsor: Bill & Melinda Gates Medical Research Institute
Sponsor class: OTHER
Collaborators: name: PPD Phase I Clinic - Orlando
First posted: 2021-11-12
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Maximum age (years): 49
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, double-blind, placebo-controlled study of RSM01. The study was 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.
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Unsolicited Treatment Emergent Adverse Events (TEAEs) Through Day 151
timeFrame: Day 1 through Day 151
measure: Number of Participants With Serious Adverse Events (SAEs) and AE of Special Interest (AESIs) Through Day 151
timeFrame: Day 1 through Day 151
measure: Number of Participants With Solicited Systemic AEs for 7 Days After Dose Administration
timeFrame: Through Day 7
measure: Number of Participants With Solicited Local AEs for Injection Site Reactions for 7 Days After Intramuscular Dose Administration
timeFrame: Up to Day 7
Secondary outcomes:
measure: Number of Participants With Clinically Significant Hematology Assessments of Grade 1 and Above Through Day 151
timeFrame: Through Day 151
measure: Number of Participants With Clinically Significant Clinical Chemistry Assessments of Grade 1 and Above Through Day 151
timeFrame: Through Day 151
measure: Area Under the Capillary Blood-concentration Time Curve From Zero to Infinity (AUC 0-infinity) After Administration of RSM01
timeFrame: Day 151
measure: Day 91 Capillary Blood-concentration (CD91) After Administration of RSM01
timeFrame: Day 91
measure: Day 91 Area Under the Capillary Blood-concentration Time Curve (AUC 0-D91) After Administration of RSM01
timeFrame: Day 91
measure: Day 151 Capillary Blood-concentration (CD151) After Administration of RSM01
timeFrame: Day 151
measure: Day 151 Area Under the Capillary Blood-concentration Time Curve (AUC 0-D151) After Administration of RSM01
timeFrame: Day 151
measure: Maximum Capillary Blood Concentration (Cmax) After Administration of RSM01
timeFrame: Day 151
measure: Minimum Capillary Blood Concentration (Cmin) After Administration of RSM01
timeFrame: Day 151
measure: Time to Maximum Capillary Blood-concentration (Tmax) After Administration of RSM01
timeFrame: Day 151
measure: Apparent Terminal Half-Life After Administration of RSM01
timeFrame: Day 151
measure: Total Body Clearance (CL) After Intravenous Dose Administration of RSM01
timeFrame: Day 151
measure: Apparent Total Body Clearance (CL) After Intramuscular Dose Administration of RSM01
timeFrame: Day 151
measure: Volume of Distribution (Vz) After Intravenous Dose Administration of RSM01
timeFrame: Day 151
measure: Apparent Volume of Distribution (Vz) After Intramuscular Dose Administration of RSM01
timeFrame: Day 151
measure: Number of Participants With Positive Anti-drug Antibodies (ADAs) at Baseline and Post-Baseline Through Day 151 Following RSM01 Administration
timeFrame: Baseline (Day 1) and post-Baseline through Day 151
Other outcomes:
Locations:
city: Orlando
country: United States
facility: PPD Phase I Clinic - Orlando
state: Florida
Study officials:
affiliation: Bill & Melinda Gates Medical Research Institute
name: Gates MRI
role: STUDY_DIRECTOR
References: