Real-World Effectiveness of Zamerovimab and Mazorelvimab and Vaccine for Rabies Grade III Exposure in Nanyang

Post-Exposure Prophylaxis Outcome of Zamerovimab and Mazorelvimab Injection and Rabies Vaccine in Grade III Rabies Exposure Cases From Single-Dog Multiple-Bite Incidents: A Real-World Prospective Study

The objective of this real-world, prospective observational study is to evaluate the clinical effectiveness of zamerovimab and mazorelvimab injection (a human rabies monoclonal antibody cocktail) administered in combination with a standard rabies vaccine for post-exposure prophylaxis (PEP) in individuals with WHO Grade III rabies exposure in Nanyang City, China.

1. The study primarily aims to assess:
2. The 3-month rabies-free survival rate following PEP initiation.
3. The 1-year long-term rabies-free survival rate.

The rabies virus (RABV) carrying rate and genomic epidemiology among offending dogs involved in single-dog multiple-bite incidents.

Eligible participants aged 18 years or older who have sustained a Grade III exposure from a tracked multi-person canine attack event, and have completed wound debridement and initial passive/active immunization within 24 hours prior to screening, will be followed for up to 1 year via telephone or clinic visits to monitor clinical survival.

Study Overview

• Status: Active, not recruiting
• Conditions: Rabies; Rabies Post-exposure Prophylaxis
• Intervention / Treatment: Drug: Zamerovimab and Mazorelvimab Injection plus Rabies Vaccine

Detailed Description

This prospective, multicenter registry study evaluates the real-world deployment, clinical protection, and safety profile of zamerovimab and mazorelvimab injection (ZM cocktail)- containing two non-overlapping human monoclonal antibodies-in community emergency settings. Rabies presents a near 100% case-fatality rate upon symptom onset, making immediate and high-potency passive immunization essential during the active-vaccine immunity window (Days 0-7). Recent regional epidemic resurgences underscore the public health urgency of handling single-dog multiple-bite clusters, where furious rabid animals carry high viral loads and inflict multiple deep lesions.Approximately 80 patients receiving routine post-exposure care will be enrolled. Participants will receive standard-of-care wound debridement, anatomical infiltration of the ZM cocktail, and a full rabies vaccine regimen. Joining this registry involves no additional clinical interventions beyond standard medical care; investigators will actively maintain follow-up contacts at 3 months and 1 year to document survival outcomes. Concurrently, trapped offending dogs will undergo molecular verification via reverse transcription polymerase chain reaction (RT-PCR) and next-generation sequencing (NGS) to map localized viral ecology, providing crucial real-world data to optimize outbreak emergency response frameworks.

• Study Type: Observational
• Enrollment (Estimated): 80

Contacts and Locations

Study Locations

• China
  • Henan
    • Nanyang, Henan, China, 473000
      • The Disease Prevention and Control Center of Nanyang

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

People aged 18 or older who were bitten by a dog that also bit others, have a serious (Grade III) rabies exposure, and already received wound cleaning, the antibody injection, and the first rabies shot within 24 hours can join.

Description

Inclusion Criteria:

1. Adults aged $\ge 18$ years at the time of screening.
2. Sustained a verified WHO Grade III rabies exposure from a traceable offending dog involved in a multi-person canine attack incident (defined as a single animal attacking multiple individuals within a clustered timeframe/location) in Nanyang City.
3. Time interval from Grade III exposure to post-exposure prophylaxis (PEP) initiation is less than 7 days.
4. Successfully completed standard wound debridement, anatomical infiltration of zamerovimab/mazorelvimab injection (0.3 mg/kg single full dose), and the first dose of rabies vaccine within 24 hours prior to screening.
5. Voluntarily provides signed written informed consent.
6. Patient is willing and able to comply with all sequential follow-up procedures (including serum collections if applicable) and intends to reside locally for the full 1-year study duration.

Exclusion Criteria:

1. Documented history of any separate animal bite or scratch (e.g., dog, cat, bat, or wild carnivore) within the past 12 months prior to the current exposure.
2. Documented complete pre-exposure or post-exposure rabies vaccination history within the past 12 months.
3. Concurrent presentation with life-threatening traumatic injuries requiring intensive care, or severe systemic immunodeficiency disorders that could impede immunogenicity or follow-up compliance.
4. Any other clinical or psychological condition deemed by the investigator as unsuitable for safe participation or reliable data registry.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Grade III rabies exposure cohort; Adults (≥18 years) who sustained verified WHO Grade III rabies exposure from a traceable dog involved in a tracked multi-person attack incident, and who initiated standardized PEP within the protocolized window.	Drug: Zamerovimab and Mazorelvimab Injection plus Rabies Vaccine; Standard-of-care wound debridement, followed by anatomical infiltration of zamerovimab/mazorelvimab injection at a single dose of 0.3 mg/kg around the wound sites on Day 0, combined with a standard intramuscular rabies vaccine regimen.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
3-month rabies-free survival rate	The proportion of participants alive and free of clinical rabies symptoms at 90 days following post-exposure prophylaxis (PEP) initiation.	90 days (±3 days) post-enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1-year rabies-free survival rate	The proportion of participants alive and free of clinical rabies symptoms at 1 year following post-exposure prophylaxis (PEP) initiation.	365 days (±7 days) post-enrollment

Collaborators and Investigators

• Sponsor: Synermore Biologics (Suzhou) Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): June 6, 2025
• Primary Completion (Actual): March 31, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: May 28, 2026
• First Submitted That Met QC Criteria: May 28, 2026
• First Posted (Actual): June 3, 2026

Study Record Updates

• Last Update Posted (Actual): June 3, 2026
• Last Update Submitted That Met QC Criteria: May 28, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Single-dog Multiple-bite Incidents; Grade III rabies exposures
• Additional Relevant MeSH Terms: Infections; RNA Virus Infections; Virus Diseases; Mononegavirales Infections; Rhabdoviridae Infections; Rabies; Biological Products; Complex Mixtures; Vaccines; Viral Vaccines; Rabies Vaccines
• Other Study ID Numbers: SYN023-RWE-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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