Phase 1, Randomized, Double-Blind, Placebo-controlled Study to Evaluate the Safety and Tolerability of an Enterovirus D68-specific Monoclonal Antibody in Healthy Adults

NCT06444048 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 23-00055UM1AI148684-04
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 2

Brief Summary

This is a Phase 1, randomized, placebo-controlled, double-blinded study to assess the safety and pharmacokinetics of single IV administrations of EV68-228-N in healthy adult volunteers. Three doses (3, 10 and 30 mg/kg) of EV68-228-N will be evaluated in three separate, sequential cohorts in this single dose escalation study. The cohorts will be randomized in a 5:1 randomization scheme. The first two participants in each cohort will serve as sentinels. Sentinel participants may be located at different sites. Sentinel safety data will be collected through Day 3 before submitting to the Protocol Safety Review Team (PSRT) for review. The PSRT is comprised of the Principal Investigator (PI), the DMID Medical Monitor, and the DMID Medical Officer. Data to be reviewed will include clinical data collected from Visits 1, 2 and 3, the results of laboratory testing conducted at these visits, solicited adverse events (AEs) and the passive reporting of adverse events through Day 3. From the time of infusion of the sentinels to at least 48 hours after infusion, no new participants will be given study product or placebo, but screening may continue. If no safety signal is detected in the sentinel group, and after approval from the DMID Medical Monitor, the remaining 10 participants in the cohort will be dosed following the overall 5:1 randomization scheme. All participants will be actively monitored for AEs and safety laboratory data following dosing through Day 8. Data will be reviewed by the PSRT and discussed with the Safety Monitoring Committee (SMC) for their concurrence before advancing to the next cohort. Electronic review of the safety data by the SMC is required prior to the cohort dose escalation when halting rules are met or there are any safety concerns. The primary objective is to evaluate the safety of a single IV infusion of either 3, 10, or 30 mg/kg of EV68-228-N when administered to healthy adults.

Conditions

Enterovirus Infection

Keywords

Antibody; Double Blind; Enterovirus; Healthy Adults; Monoclonal; Placebo Controlled; Randomized

Outcome Measures

Primary Outcomes (3)

• Number of Participants Experiencing Solicited Adverse Events (AEs) Through 48 Hours Post-infusion

  Number of participants in each treatment group experiencing at least one solicited AE of any severity through 48 hours post-infusion

  Day 1 (post-infusion) through 48 hours post-infusion

• Number of Participants Experiencing Unsolicited AEs - Including Clinical and Laboratory AEs - Through Day 29

  Number of participants in each treatment group experiencing at least one unsolicited AE - including clinical and laboratory AEs - through Day 29

  Day 1 (post-infusion) through Day 29

• Number of Participants Experiencing Unsolicited Serious Adverse Events (SAEs), Medically Attended Adverse Events (MAAEs), and New Onset Chronic Medical Conditions (NOCMCs) Through the End of the Study

  Number of participants in each treatment group experiencing at least one SAE, MAAE, or NOCMC through the end of the study.

  Day 1 (post-infusion) through Day 121

Secondary Outcomes (9)

• Area Under the Concentration-time Curve From Time 0 (Time of Infusion Start, t=0 Hours) to the Last Quantifiable Concentration (AUC0-last) of EV68-228-N in Serum

  Prior to infusion; end of infusion; 1, 3, 5, 24, and 48 hours after end of infusion; Days 8, 15, 29, 61, 91, and 121

• Area Under the Concentration-time Curve From Time 0 (Time of Infusion Start, t=0 Hours) to Infinity (AUC0-infinity) of EV68-228-N in Serum

  Prior to infusion; end of infusion; 1, 3, 5, 24, and 48 hours after end of infusion; Days 8, 15, 29, 61, 91, and 121

• Area Under the Concentration-time Curve From Time 0 (Time of Infusion Start, t=0 Hours) to 48 Hours Post-dose (AUC0-48) of EV68-228-N in Serum

  Prior to infusion; end of infusion; 1, 3, 5, 24, and 48 hours after end of infusion

• Maximum Observed Serum Concentration (Cmax) of EV68-228-N in Serum

  Prior to infusion; end of infusion; 1, 3, 5, 24, and 48 hours after end of infusion; Days 8, 15, 29, 61, 91, and 121

• Time of Maximum Observed Serum Concentration (Tmax) of EV68-228-N in Serum

  Prior to infusion; end of infusion; 1, 3, 5, 24, and 48 hours after end of infusion; Days 8, 15, 29, 61, 91, and 121

Study Arms (6)

Cohort 1A

EXPERIMENTAL

Healthy adult participants will be randomized at a 5:1 ratio. 10 participants to receive a 3 mg/kg single intravenous infusion of EV68-228-N and 2 Participants matching Placebo (20mM Citrate + 10 mM Glycine, 8% Sucrose, and 0.01% Polysorbate 80)

Biological: EV68-228-N

Cohort 1B

PLACEBO COMPARATOR

Healthy adult participants will be randomized at a 5:1 ratio. 10 participants to receive a 3 mg/kg single intravenous infusion of EV68-228-N and 2 Participants matching Placebo (20mM Citrate + 10 mM Glycine, 8% Sucrose, and 0.01% Polysorbate 80)

Other: Placebo for EV68-228-N

Cohort 2A

EXPERIMENTAL

Healthy adult participants will be randomized at a 5:1 ratio to receive a single intravenous infusion of EV68-228-N and Placebo (20mM Citrate + 10 mM Glycine, 8% Sucrose, and 0.01% Polysorbate 80) 10 mg/kg. N=2

Biological: EV68-228-N

Cohort 2B

PLACEBO COMPARATOR

Healthy adult participants will be randomized at a 5:1 ratio to receive a single intravenous infusion of EV68-228-N and Placebo (20mM Citrate + 10 mM Glycine, 8% Sucrose, and 0.01% Polysorbate 80) 10 mg/kg. N=2

Other: Placebo for EV68-228-N

Cohort 3A

EXPERIMENTAL

Healthy adult participants will be randomized at a 5:1 ratio to receive a single intravenous infusion of EV68-228-N N=10 and Placebo (20mM Citrate + 10 mM Glycine, 8% Sucrose, and 0.01% Polysorbate 80) 30 mg/kg. N=2

Biological: EV68-228-N

Cohort 3B

PLACEBO COMPARATOR

Healthy adult participants will be randomized at a 5:1 ratio to receive a single intravenous infusion of EV68-228-N N=10 and Placebo (20mM Citrate + 10 mM Glycine, 8% Sucrose, and 0.01% Polysorbate 80) 30 mg/kg. N=2

Other: Placebo for EV68-228-N

Interventions

EV68-228-N BIOLOGICAL

EV68-228-N is a recombinant human monoclonal IgG1 antibody which is produced by genetically engineered plasmids in Nicotiana benthamiana. This intervention is directed against enterovirus EV-D68 capsid protein potentially providing treatments for EV-D68 infection and AMF.

Cohort 1A; Cohort 2A; Cohort 3A

Placebo for EV68-228-N OTHER

The placebo is a sterile buffer solution formulated to match the EV68-228-N Drug Product. The formulation is 20mM Citrate + 10 mM Glycine, 8% Sucrose, and 0.01% Polysorbate 80, with a target pH of 5.5. The placebo will be filled into glass vials at 10 mL per vial. The formulation buffer is a clear colorless liquid.

Cohort 1B; Cohort 2B; Cohort 3B

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Provides written informed consent prior to initiation of any study procedures.
• Is able to understand and agrees to adhere to planned study procedures and is available for all study visits.
• Adult volunteers 18 to 49 years of age, inclusive.
• Females who are of childbearing potential must agree not to become pregnant. Not of childbearing potential includes post-menopausal females (defined as no menses for at least 12 months without an alternative medical cause for amenorrhea) or surgically sterile females with documented history of hysterectomy, bilateral oophorectomy, tubal ligation/salpingectomy, or Essure(R) placement.
• Females who have sexual intercourse with male partners must agree to use at least one acceptable form of contraception for the duration of the study.
• Acceptable methods of birth control include long-acting reversible contraception (LARC), combined pill, progestin-only pill, hormone-releasing transdermal patch or vaginal ring, and depot medroxyprogesterone acetate (DMPA) injection. Participants who choose to use a licensed hormonal product should use them for a minimum of 28 days prior to study infusion. True sexual abstinence or a monogamous relationship with a vasectomized partner who has been vasectomized for 180 days or more prior to the participant's first infusion are also acceptable contraceptive methods.
• Participants who report practicing true abstinence, defined as no heterosexual vaginal-penile intercourse, need to practice true abstinence at all times during the study. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and the withdrawal method are not acceptable methods of contraception.
• Females of childbearing potential must agree to not donate ova or oocytes during the study.

You may not qualify if:

• Must agree to refrain from donating blood or blood products during the study. This includes whole blood cells, red blood cells, platelets, plasma, and plasma derivatives collected and donated outside of the study blood draws.
• Body mass index (BMI) 18 kg/m2 to 32 kg/m2, inclusive, and a weight of 125 kg or less at time of screening.
• Must have adequate venous access for intravenous (IV) infusion and blood sampling.
• Positive pregnancy test at screening or prior to infusion.
• Female participant who is lactating.
• Presence of significant psychiatric condition, that in the opinion of the site PI or appropriate sub-investigator, precludes study participation.
• History of drug abuse or alcohol abuse within 6 months of enrollment that, in the opinion of the site PI or appropriate sub-investigator, precludes study participation.
• Has a significant acute illness (with or without fever), as determined by the site PI or appropriate sub-investigator, within 72 hours prior to infusion.
• If the participant meets all other eligibility criteria, they may be enrolled and dosed once they meet this eligibility criterion. If the illness resolves within the 28-day screening window, they do not need to be rescreened, otherwise they will need to be rescreened.
• Currently enrolled in or plans to participate in another clinical trial with an investigational agent that will be received during the study-reporting period.
• Has a history of significant hypersensitivity, intolerance, or allergy to any drug compound, vaccine, food, or other substance, unless approved by the Investigator (or designee).
• Any history of an infusion reaction to any biologic product.
• Receipt of a monoclonal antibody in the 180 days prior to infusion.
• Receipt of a blood product within 120 days prior to infusion.
• Received any live-attenuated vaccine in the 28 days prior or any other vaccine in the 14 days prior to infusion.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• KBio Inc: collaborator

Study Sites (2)

University of Maryland, School of Medicine, Center for Vaccine Development and Global Health

Baltimore, Maryland, 21201-1509, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232-0011, United States

Location

Related Publications (1)

• Rudy MJ, Wilson CJ, Hinckley B, Baker DC, Royal JM, Hoke MP, Brennan MB, Vogt MR, Clarke P, Tyler KL. EV68-228-N monoclonal antibody treatment halts progression of paralysis in a mouse model of EV-D68 induced acute flaccid myelitis. mBio. 2025 Apr 9;16(4):e0390624. doi: 10.1128/mbio.03906-24. Epub 2025 Mar 24.

  PMID: 40126012 DERIVED

MeSH Terms

Conditions

Enterovirus Infections

Condition Hierarchy (Ancestors)

Picornaviridae Infections; RNA Virus Infections; Virus Diseases; Infections

Results Point of Contact

• Title: C. Buddy Creech, MD, MPH
• Organization: Vanderbilt University Medical Center

buddy.creech@vumc.org

615-343-0332

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Participants, investigators, study personnel performing any study-related assessments following study product administration, and laboratory personnel will be blinded to treatment assignments.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 16, 2024
• First Posted: June 5, 2024
• Study Start: June 26, 2024
• Primary Completion: April 11, 2025
• Study Completion: April 11, 2025
• Last Updated: May 4, 2026
• Results First Posted: May 4, 2026

Record last verified: 2026-03-23

Locations

US (2)