A Bridging Study of the SYN023 on Healthy Adult Subjects

NCT04495569 | Completed Phase 1 FDA Drug

• 1 other identifier: SYN023-005
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

The Phase I bridging clinical trial is to evaluate on the safety, pharmacokinetics (PK), pharmacodynamics (PD) and ADA of a single intramuscular injection of recombinant anti-rabies human monoclonal antibody injection (SYN023) alone or combined with rabies vaccine in healthy subjects. The study primary purpose was to compare the pharmacokinetics (PK) between U.S and China subjects, therefore to lay a foundation for the follow-up clinical trials. The secondary purpose was to evaluate the PK, PD, Safety and ADA of SYN023 in Chinese Healthy subjects and compare with that of U.S. subjects.

Conditions

Communicable Disease Transmission; Zoonotic Disease; Rabies Human; Vaccine Reaction; Immunisation Reaction

Keywords

Bridging study; Rabies Vaccine; Monoclonal Antibody Cocktail; Biologics,

Outcome Measures

Primary Outcomes (5)

• To compare the Tmax between Chinese and American subjects with a single dose of 0.3 mg/kg SYN023 alone or combined with rabies vaccine

  Interval from time 0 to maximum measured concentration of CTB011 and CTB012 (SYN023 components) at Day1-0 h (pre-dose), Day1-6 h, Day2(24 h), Day3(48 h), Day4(72 h), Day6(120 h), Day8(168 h), Day15(336 h), Day29(672 h), Day36(840 h), Day43(1008 h), Day64(1512 h), Day85(2016 h) post-dose, using non compartmental analysis.

  85 days

• To compare the Cmax between Chinese and American subjects with a single dose of 0.3 mg/kg SYN023 alone or combined with rabies vaccine.

  maximum concentration of CTB011 and CTB012 (SYN023 components) at Day1-0 h (pre-dose), Day1-6 h, Day2(24 h), Day3(48 h), Day4(72 h), Day6(120 h), Day8(168 h), Day15(336 h), Day29(672 h), Day36(840 h), Day43(1008 h), Day64(1512 h), Day85(2016 h) post-dose, using non compartmental analysis.

  85 days

• To compare the t1/2 between Chinese and American subjects with a single dose of 0.3 mg/kg SYN023 alone or combined with rabies vaccine.

  The half life of CTB011 and CTB012 (SYN023 components) were estimated at Day1-0 h (pre-dose), Day1-6 h, Day2(24 h), Day3(48 h), Day4(72 h), Day6(120 h), Day8(168 h), Day15(336 h), Day29(672 h), Day36(840 h), Day43(1008 h), Day64(1512 h), Day85(2016 h) post-dose, using non compartmental analysis.

  85 days

• To compare the Clearance rate between Chinese and American subjects with a single dose of 0.3 mg/kg SYN023 alone or combined with rabies vaccine.

  The clearance rate of CTB011 and CTB012 (SYN023 components) were estimated at at Day1-0 h (pre-dose), Day1-6 h, Day2(24 h), Day3(48 h), Day4(72 h), Day6(120 h), Day8(168 h), Day15(336 h), Day29(672 h), Day36(840 h), Day43(1008 h), Day64(1512 h), Day85(2016 h) post-dose, using non compartmental analysis.

  85 days

• SYN023 Monoclonal Antibody Areas Under the Curve (AUC0-last, AUC0-inf) for CTB011 and CTB012

  The area under the time concentration curve for SYN023 mAb components CTB011 and CTB012 were estimated at at Day1-0 h (pre-dose), Day1-6 h, Day2(24 h), Day3(48 h), Day4(72 h), Day6(120 h), Day8(168 h), Day15(336 h), Day29(672 h), Day36(840 h), Day43(1008 h), Day64(1512 h), Day85(2016 h) post-dose, using non compartmental analysis

  85 days

Secondary Outcomes (4)

• Percentage of Participants With Adverse Event Incidence of healthy adult recipients of a single-dosed SYN023 0.3 mg/kg alone or combined with Rabies Vaccine

  85 days

• To evaluate the antibody protection level RVNA (Rabies Virus Neutralizing Antibodies)≥ 0.5 IU/mL of serum from healthy adult recipients of a single-dosed SYN023 0.3 mg/kg alone or combined with Rabies Vaccine

  85 days

• To evaluate the RVNA (Rabies Virus Neutralizing Antibodies) of serum from healthy adult recipients of a single-dosed SYN023 0.3 mg/kg alone or combined with Rabies Vaccine

  85 days

• To evaluate the ADA (Anti-Drug Antibodies) of serum from healthy adult recipients of a single-dosed SYN023 0.3 mg/kg alone or combined with Rabies Vaccine

  85 days

Study Arms (2)

Group/Cohort A

EXPERIMENTAL

A single intramuscular injection of SYN023 at 0.3mg/kg

Biological: recombinant anti-rabies human monoclonal antibody injection (SYN023)

Group/Cohort B

EXPERIMENTAL

A single intramuscular injection of SYN023 at 0.3mg/kg combined with the Chinese licensed Vero Cell Rabies Vaccine (following the PEP (Post-exposure Prophylaxis) recommendation)

Biological: recombinant anti-rabies human monoclonal antibody injection (SYN023); Biological: Rabies Vaccine

Interventions

recombinant anti-rabies human monoclonal antibody injection (SYN023) BIOLOGICAL

The finished product of SYN023 is a mixture of two anti-rabies human monoclonal antibodies, CTB011 and CTB012 by equal quantity, containing 3.0 mg/mL active ingredients in both.

Group/Cohort A; Group/Cohort B

Rabies Vaccine BIOLOGICAL

The Chinese licensed Vero Cell Freeze-dried Rabies Vaccine was injected to Cohort B as per the vaccination precedure on Days 1, 4, 8, 15, 28 respectively.

Group/Cohort B

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Sign the informed consent before the trial, fully understand the trial contents, process and possible adverse reactions, and cooperate to observe the adverse events;
• Could participate the entire study according to the protocol;
• Subjects including partners are willing to voluntarily take effective contraceptive measures from screening to 6 months after the last study drug administration.
• Male and female healthy subjects aged 18-50 (including 18 and 50 years old)
• The weight of male subjects shall not be less than 50 kg, and that of female subjects shall not be less than 45 kg and shall not be more than 90 kg. Body mass index (BMI) = body weight (kg) / height\^2 (m\^2), body mass index should be in the range of 18-30 kg/m2 (including);
• Physical examination and vital signs are in normal range or the abnormality without clinical significance, and the body temperature is ≤ 37.6 °C.

You may not qualify if:

• Smoked over 5 cigarettes per day for 3 months before the trial;
• History of allergy (multi drugs and food allergy); history of severe allergic disease or allergic reaction; including allergy to any component of this drug;
• History of alcohol addiction (14 units of alcohol per week: 1 unit = 285 mL beer, or 25 mL spirits, or 100 mL wine);
• Blood donation or massive blood loss (\> 450 mL) occurred within 3 months before screening;
• History of autoimmune diseases;
• History of chronic hepatitis ;
• History of rabies virus infection;
• Other acute or chronic diseases (within 6 months) that may interfere with the safety and efficacy evaluation of the subjects according to the investigator's judgment;
• Receipt of an immunoglobulin or blood product within 90 days prior to study;
• History of rabies vaccination;
• Receipt of immunosuppressive medications included the inhaled or local immunosuppressant drugs within 45 days prior to Study;
• Taken any prescribed, over-the-counter, vitamin product or herbal medicine within 14 days before screening;
• Receipt of special diets (such as grapefruit) or endure strenuous physical exercise or any other factors affecting drug absorption, distribution, metabolism and excretion within 2 weeks before screening;
• Had significant changes in diet or exercise habits recently;
• Had been administrated with the investigational drug or participated in the clinical trial of the drug within three months before taking the investigational drug;

Sponsors & Collaborators

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

Study Sites (1)

Jilin University

Changchun, Jilin, China

Location

Related Publications (3)

• Chao TY, Zhang SF, Chen L, Tsao E, Rupprecht CE. In Vivo Efficacy of SYN023, an Anti-Rabies Monoclonal Antibody Cocktail, in Post-Exposure Prophylaxis Animal Models. Trop Med Infect Dis. 2020 Feb 21;5(1):31. doi: 10.3390/tropicalmed5010031.

  PMID: 32098049 BACKGROUND

• Chao TY, Ren S, Shen E, Moore S, Zhang SF, Chen L, Rupprecht CE, Tsao E. SYN023, a novel humanized monoclonal antibody cocktail, for post-exposure prophylaxis of rabies. PLoS Negl Trop Dis. 2017 Dec 20;11(12):e0006133. doi: 10.1371/journal.pntd.0006133. eCollection 2017 Dec.

  PMID: 29261658 RESULT

• Ding Y, Wu M, Zhang H, Zhu X, Hu Y, Li X, Liu J, Tsao E, Liu M, Li C. Safety, pharmacokinetics and pharmacodynamics of SYN023 alone or in combination with a rabies vaccine: An open, parallel, single dose, phase 1 bridging study in healthy Chinese subjects. Antiviral Res. 2020 Dec;184:104956. doi: 10.1016/j.antiviral.2020.104956. Epub 2020 Oct 19.

  PMID: 33091433 RESULT

MeSH Terms

Conditions

Zoonoses

Interventions

Rabies Vaccines

Condition Hierarchy (Ancestors)

Infections; Animal Diseases

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Cohort A: Intramuscular 0.3 mg/kg SYN023 Cohort B: Intramuscular 0.3 mg/kg SYN023 + China licensed Vero Cell Rabies Vaccine (PEP)

Study Record Dates

• First Submitted: May 10, 2020
• First Posted: August 3, 2020
• Study Start: February 26, 2019
• Primary Completion: June 20, 2019
• Study Completion: February 20, 2020
• Last Updated: September 29, 2021

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)