AzTrials
AzTrials

Communicable Disease TransmissionPhase 1/2NCT04495569

A Bridging Study of the SYN023 on Healthy Adult Subjects

A Phase 1/2 study testing recombinant anti-rabies human monoclonal antibody injection (SYN023) and Rabies Vaccine in people with Communicable Disease Transmission and Zoonotic Disease, run by Synermore Biologics (Suzhou) Co., Ltd. at 1 site in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 50 yearsHealthy volunteers can take part
What is being tested?
recombinant anti-rabies human monoclonal antibody injection (SYN023) and Rabies Vaccine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
33 participants
Where
1 siteChina
Study dates
26 Feb 2019to 20 Feb 2020
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 50 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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.

Who cannot join

  • 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 ;
Show all 34Show fewer
  • 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;
  • The evidence of clinically significant of the abnormalities of 12 lead ECG ;
  • Female subjects in lactation or positive for serum pregnancy test during screening for study;
  • Clinical significance of clinical laboratory results of screening, or suffered from the following diseases, including but not limited to gastrointestinal tract, kidney, liver, nerve, blood, endocrine, tumor, lung, immune, mental or cardio cerebrovascular diseases within 6 months;
  • Positive in the screening of viral hepatitis (including hepatitis B and C), AIDS antibody, and treponema pallidum antibody;
  • Acute disease or drug administration from the screening to the initial of the study;
  • History of taken chocolate, or any food or drink containing caffeine or rich xanthine 24 hours prior to administration of the study drug;
  • History of taken any alcoholic product within 24 hours prior to administration of the study drug;
  • Drug abuse ;
  • Not suitable for enrolling in the study according to the investigator's judgment.
  • Additional exclusion criteria for Group B:
  • Clinical significance of Immunoglobulin A abnormalities according to the investigator's judgment;
  • Undergoing anti-tuberculosis prophylaxis or treatment;
  • History of thyroidectomy, or treatment due to thyroid diseases in the past 12 months;
  • Diagnosed with serious angioneurotic edema in past 3 years or with the treatment in the past two years prior to the study;
  • Advanced tumors, or neoplasm in treatment and shows no evidence of recovery, or may relapse during the study;
  • No spleen or history of splenectomy;
  • Guillain-Barre syndrome or other serious neuropathy;
  • Receipt of live-attenuated vaccine within 30 days prior to the study;
  • Receipt of subunit or inactivated vaccine (such as pneumococcal vaccine), or allergy treatment within 14 days prior to the study;

Trial locations and contacts

1 site in 1 country.

China1 site
  • Jilin University

    Changchun, Jilin

Other trials in China

About this study

Official title: A Phase 1 Single Center, Parallel, Open Label Bridging Study to Evaluate on the Safety, Pharmacokinetic, Pharmacodynamics and Anti-drug Antibodies (ADA) of a Single Intramuscular Doses of SYN023 in Healthy Adult Subjects

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.

Read the detailed description

In this bridging study. the Pharmacodynamic, Pharmacokinetic, Safety and ADA(Anti-Drug Antibodies) were evaluated and compared between U.S. and China subjects.

Being tested
recombinant anti-rabies human monoclonal antibody injection (SYN023), Rabies Vaccine
Keywords
Bridging study, Rabies Vaccine, Monoclonal Antibody Cocktail, Biologics,
Medical subject headings
Zoonoses

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 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.

  • Rabies VaccineBiological

    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.

Study groups in NCT04495569
Study groupRoleWhat they receive
Group/Cohort AExperimentalA single intramuscular injection of SYN023 at 0.3mg/kg
Receives: Biological: recombinant anti-rabies human monoclonal antibody injection (SYN023)
Group/Cohort BExperimentalA 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)
Receives: Biological: recombinant anti-rabies human monoclonal antibody injection (SYN023); Biological: Rabies Vaccine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 85 days

  2. 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.

    Measured: 85 days

  3. 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.

    Measured: 85 days

  4. 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.

    Measured: 85 days

  5. 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

    Measured: 85 days

Secondary outcomes (4)
  1. 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

    Electrocardiograms are performed to monitor subject safety. Laboratory evaluations for subject safety (adverse events) are serum chemistry evaluations, blood urea nitrogen, creatinine, bilirubin, alanine amino transferase, aspartate amino transferase, creatine phosphokinase, troponin, potassium, sodium, bicarbonate, calcium, complete blood count, platelet count, differential count, PT(prothrombin time, international normalized ratio) and PTT (partial prothrombin time and urinalyses for monitoring of safety. Additional laboratory tests may be required for evaluation of specific adverse events such as anaphylaxis and immune complex diseases. Adverse events were analyzed. A comparison of adverse event incidence between a single-dosed SYN023 0.3 mg/kg alone or combined with Rabies Vaccine were performed.

    Measured: 85 days

  2. 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

    parallel the Cohort A and Cohort B to compare the antibody protection level (RVNA ≥ 0.5 IU/mL) between China and U.S. subjects

    Measured: 85 days

  3. 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

    parallel the Cohort A and Cohort B to compare the RVNA between China and U.S. subjects

    Measured: 85 days

  4. 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

    parallel the Cohort A and Cohort B to compare the ADA between China and U.S. subjects

    Measured: 85 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Aug 2020
  2. Study start26 Feb 2019
  3. Primary completion20 Jun 2019
  4. Study completion20 Feb 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Model description
Cohort A: Intramuscular 0.3 mg/kg SYN023 Cohort B: Intramuscular 0.3 mg/kg SYN023 + China licensed Vero Cell Rabies Vaccine (PEP)
Masking
None (open label)
Enrolment
33 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04495569
Sponsor's protocol ID
SYN023-005
Status last verified
Jun 2020
First submitted
10 May 2020
Last updated
29 Sep 2021
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 32098049
  • 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.

    PubMed 29261658
  • 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.

    PubMed 33091433

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing recombinant anti-rabies human monoclonal antibody injection (SYN023) and Rabies Vaccine in people with Communicable Disease Transmission and Zoonotic Disease, run by Synermore Biologics (Suzhou) Co., Ltd. at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 (time frame: 85 days). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04495569, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Sep 2021.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in