A Phase 3 Clinical Trial to Evaluate Long-term Immunogenicity and Boostability of Purified Chick-Embryo Cell Rabies Vaccine in Adults Following Primary Series of Pre/Exposure Prophylaxis.

Browse trials for

• Virus Diseases 656Registry's first term
• Rabies 114Primary · reclassified

Keywords

• Rabies disease
• Pre-exposure (PrEP) or post exposure prophylaxis (PEP)
• Long-term Immunogenicity

Rabies Reclassified

114 studies on the registry are indexed under Rabies; 15 are open to participants now.

This study's enrollment of 459 is above the median of 201 across 104 interventional studies indexed under Rabies.

Lead sponsor

GlaxoSmithKline is the lead sponsor of 3,650 studies on the registry; 118 are open to participants now.

Of its 264 completed or terminated interventional studies of FDA-regulated products, 241 (91%) have results posted.

Study arms

• Experimental
  Conv-R/JE Group

  Participants who completed the Rabies PrEP regimen on days 1, 8 and 29, and Japanese Encephalitis (JE) primary series regimen on days 1 and 29 in the parent study (V49_23) and who received at least one booster dose of purified chick embryo cell culture (PCEC) rabies vaccine in this extension study, if Rabies Virus Neutralizing Antibody (RNVA) concentrations were less than (\<)0.5 IU/mL at scheduled visits.

  Biological: Rabipur · Procedure: Blood sampling · Biological: Purified Chick-Embryo Cell Rabies Vaccine

• Experimental
  Acc-R/JE Group

  Participants who completed the Rabies PrEP regimen on days 1, 4 and 8 and JE primary series regimen on days 1 and 8 in the parent study (V49_23) and who received at least one booster dose of PCEC rabies vaccine in this extension study, if RNVA concentrations were \<0.5 IU/mL at scheduled visits.

  Biological: Rabipur · Procedure: Blood sampling

• Experimental
  Conv-R Group

  Participants who completed the Rabies PrEP regimen on days 1, 8 and 29 in the parent study (V49_23) and who received at least one booster dose of PCEC rabies vaccine in this extension study, if RNVA concentrations were \<0.5 IU/mL at scheduled visits.

  Biological: Rabipur · Procedure: Blood sampling

Interventions

• BiologicalRabipur

  Participants in all the groups received Rabipur vaccine booster dose, administered intramuscularly in the deltoid region of the non-dominant arm.

• ProcedureBlood sampling

  Blood samples were drawn from all participants at Day 1 and then at subsequent year intervals from extension study Day 1 onwards.

• BiologicalPurified Chick-Embryo Cell Rabies Vaccine

  1 booster dose of 1.0 mL of Purified Chick-Embryo Cell Rabies Vaccine intramuscular (IM).

Primary outcomes

1. Number of Participants Reporting Serious Adverse Events (SAEs) After a Booster Dose of Purified Chick Embryo Cell Culture (PCEC) Rabies Vaccine

   A SAE is defined as any untoward medical occurrence that at any dose results in one or more of the following: death, is life-threatening, required/prolonged hospitalization, persistent or significant disability/incapacity, congenital anomaly/or birth defect, an important and significant medical event that may not be immediately life threatening or resulting in death or hospitalization but, based upon appropriate medical judgment, may jeopardize the participants or may require intervention to prevent one of the other outcomes listed. Safety is assessed as the number of participants reporting SAEs after a booster dose of PCEC rabies vaccine administered in this extension study, if RNVA concentrations were \<0.5 IU/mL, following a primary series of accelerated or conventional rabies pre-exposure (PrEP) intramuscular (IM) regimen in the parent study.

   Time frame: From booster vaccination [6 to 9 months after Year 3 (3 years after primary series of vaccination)] up until completion of the safety follow-up period (10 years after primary series of vaccination)

2. Number of Participants Who Had Their Rabies Virus Neutralizing Antibody (RNVA) Concentrations Drop Below 0.5 International Units (IU) Per Milliliter (mL) Between Day 366 and Year 3

   Time frame: Day 366 to Year 3 (after primary series of vaccination)

3. Number of Participants Who Had Their RNVA Concentrations Drop Below 0.5 IU/mL Between Year 3 and Year 4

   Time frame: Year 3 to Year 4 (after primary series of vaccination)

4. Number of Participants Who Had Their RNVA Concentrations Drop Below 0.5 IU/mL Between Year 4 and Year 5

   Time frame: Year 4 to Year 5 (after primary series of vaccination)

5. Number of Participants Who Had Their RNVA Concentrations Drop Below 0.5 IU/mL Between Year 5 and Year 6

   Time frame: Year 5 to Year 6 (after primary series of vaccination)

6. Number of Participants Who Had Their RNVA Concentrations Drop Below 0.5 IU/mL Between Year 6 and Year 7

   Time frame: Year 6 to Year 7 (after primary series of vaccination)

7. Number of Participants Who Had Their RNVA Concentrations Drop Below 0.5 IU/mL Between Year 7 and Year 8

   Time frame: Year 7 to Year 8 (after primary series of vaccination)

8. Number of Participants Who Had Their RNVA Concentrations Drop Below 0.5 IU/mL Between Year 8 and Year 9

   Time frame: Year 8 to Year 9 (after primary series of vaccination)

9. Number of Participants Who Had Their RNVA Concentrations Drop Below 0.5 IU/mL Between Year 9 and Year 10

   Time frame: Year 9 to Year 10 (after primary series of vaccination)

10. RVNA Antibody Concentrations 7 Days After the Booster Dose

    RVNA antibody concentrations were measured in terms of Geometric Mean Concentrations (GMCs) and expressed in IU/mL. The booster dose was administered in this Extension study (conducted from Year 3 to Year 9 after the primary schedule study) only when participants had RVNA concentrations \<0.5 IU/mL at the yearly immunogenicity check (i.e., at "Scheduled Clinic Visit"). Booster dose administration occurred at an approximate timepoint between 6 and 9 months from the previous "Scheduled Clinic Visit" during the Years 3 to 9.

    Time frame: At Day 7 after booster dose

11. RVNA Geometric Mean Ratios (GMRs) 7 Days After the Booster Dose Versus Antibody Concentrations Before the Booster Dose

    GMR was calculated as ratio of post booster dose RVNA GMCs (7-day post booster dose) to the baseline RVNA GMCs (7 days before booster dose). The booster dose was administered in this Extension study (conducted from Year 3 to Year 9 after the primary schedule study) only when participants had RVNA concentrations \<0.5 IU/mL at the yearly immunogenicity check (i.e., at "Scheduled Clinic Visit"). Booster dose administration occurred at an approximate timepoint between 6 and 9 months from the previous "Scheduled Clinic Visit" during the Years 3 to 9.

    Time frame: Day 7 after booster dose compared to baseline (7 days before booster dose)

12. Percentage of Participants With RVNA Concentrations Greater Than or Equal to (>=) 0.5 IU/mL, 7 Days After Booster Dose

    The booster dose was administered in this Extension study (conducted from Year 3 to Year 9 after the primary schedule study) only when participants had RVNA concentrations \<0.5 IU/mL at the yearly immunogenicity check (i.e., at "Scheduled Clinic Visit"). Booster dose administration occurred at an approximate timepoint between 6 and 9 months from the previous "Scheduled Clinic Visit" during the Years 3 to 9.

    Time frame: At Day 7 after booster dose

13. Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 3

    Time frame: At Year 3 after primary series of vaccine administration

14. Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 4

    Time frame: At Year 4 after primary series of vaccine administration

15. Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 5

    Time frame: At Year 5 after primary series of vaccine administration

16. Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 6

    Time frame: At Year 6 after primary series of vaccine administration

17. Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 7

    Time frame: At Year 7 after primary series of vaccine administration

18. Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 8

    Time frame: At Year 8 after primary series of vaccine administration

19. Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 9

    Time frame: At Year 9 after primary series of vaccine administration

20. Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 10

    Time frame: At Year 10 after primary series of vaccine administration

Secondary outcomes

1. Rabies Virus Neutralizing Antibody Concentrations

   Antibody concentrations were measured in terms of GMCs and expressed in IU/mL.

   Time frame: At Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and Year 10 after primary series of vaccine administration

2. Reverse Cumulative Percentage for Participants With RVNA Concentrations >=0.5 IU/mL

   As specified in the statistical analysis plan, a graphical presentation of the Reverse Cumulative Distribution Plots for participants with RVNA concentrations \>=0.5 IU/mL was analyzed for this outcome measure. Due to system constrains, only the reverse cumulative percentage values were reported, to depict the Reverse Cumulative Distribution Plots.

   Time frame: At Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and Year 10 after primary series of vaccine administration

Baseline characteristics

Study documents

• Study protocol ↗ · Feb 25, 2019
• Statistical analysis plan ↗ · Feb 23, 2022

PDFs hosted by the registry, ClinicalTrials.gov.