Safety and Efficacy of Two Tetanus-Diphtheria Vaccines for a Donor Hyper Immunization Program

Many plasma donation centers have Tetanus immunization programs that are implemented in order to collect plasma with high levels of tetanus antibodies. The immunization program requires participants to receive multiple tetanus vaccinations over a period of time with the goal of hyper-immunizing them to tetanus. Their antibody-rich plasma is then used to manufacture a tetanus immunoglobulin product which helps with the prophylaxis and treatment of tetanus disease.

The Tetanus vaccine previously used for these programs is no longer being manufactured. Therefore, we must evaluate the safety and efficacy of a different vaccine when used for this purpose. The only other FDA approved Tetanus vaccines currently available for adults in the US are combination vaccines that also immunize against Diphtheria and/or Pertussis.

In this study, the investigators will evaluate two vaccines that are combinations of Tetanus and Diphtheria (Td). Investigators will not evaluate any vaccines containing Pertussis antigen. The vaccines to be evaluated are manufactured by MassBiologics and Sanofi Pasteur (Tenivac).

The package insert for these vaccines indicates they should be administered to previously vaccinated people once every 10 years. However, this study will evaluate whether they are safe and effective for dosing every 90 days.

The investigators hypothesize that at least 25% of study subjects will have a positive response to at least one of the five planned doses. Each vaccine will be evaluated separately.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Biological: Tetanus and Diphtheria (Td) Vaccine

• Study Type: Interventional
• Enrollment (Actual): 300
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Bellflower, California, United States, 90706
      • Biomat Bellflower
  • Nebraska
    • Lincoln, Nebraska, United States, 68510
      • Biomat Lincoln
  • Tennessee
    • Clarksville, Tennessee, United States, 37042
      • Biomat Clarksville
  • Utah
    • Salt Lake City, Utah, United States, 84116
      • Biomat Salt Lake City 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 69 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female ≥18* years of age at Visit 1.
2. Subject has met all suitability criteria that would allow donation as a Normal Source Plasma donor
3. Subject has not been immunized for tetanus within the prior three (3) months
4. Subject is not participating in any other immunization program
5. Subject possesses a pre-existing antibody for tetanus of at least 0.15 IU/mL

Exclusion Criteria:

1. Pregnant.
2. Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.
3. Subject has a hypersensitivity to components in the vaccine (e.g., thimerosal, latex, etc.)
4. Subject has history of a severe reaction to any immunization
5. Subject has a history of Guillain-Barré Syndrome
6. Subject is unable to read and/or write due to illiteracy or a physical impairment.

7. The Investigator concludes that the anticipated vaccination site (deltoid area) is not suitable for adverse event assessment

   • Or legal adult according to local law. Participants in NE limited to individuals age 19-69 years due to age of majority laws in NE.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sanofi Pasteur (Tenivac); Tetanus and Diphtheria (Td) Vaccine, Manufacturer: Sanofi Pasteur (Tenivac), Dose: 0.5 mL, Route: Intramuscular (IM) in the deltoid muscle, Frequency: Every 90 days, Duration: 5 doses, 1 year.	Biological: Tetanus and Diphtheria (Td) Vaccine
Experimental: MassBiologics; Tetanus and Diphtheria (Td) Vaccine, Manufacturer: MassBiologics, Dose: 0.5 mL, Route: Intramuscular (IM) in the deltoid muscle, Frequency: Every 90 days, Duration: 5 doses, 1 year.	Biological: Tetanus and Diphtheria (Td) Vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of participants with a positive tetanus titer response following immunization	A "positive response" is defined as a 4-fold increase if the pre-vaccination titer was less than or equal to 2.7IU/mL or a 2-fold increase if the pre-vaccination titer was greater than 2.7IU/mL	Through study completion, average 18 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants experiencing vaccine-related adverse events	Number of related adverse events will be compared with prescribing information for the vaccine and with historic data on adverse event rates among Normal Source plasma donors and Hyper-Immunized plasma donors. Severity grading of vaccine-related adverse events is based on a modified version of FDA guidance dated September 2007 titled "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials."	Through study completion, average 18 months.

Collaborators and Investigators

• Sponsor: Biomat USA, Inc.
• Collaborators: Axio Research. LLC; Hammond Clinical Trial Consulting, LLC
• Investigators: Principal Investigator: Marilyn Rosa-Bray, MD, Biomat USA, Inc. (Sponsor)

Study record dates

Study Major Dates

• Study Start (Actual): August 22, 2016
• Primary Completion (Actual): July 29, 2019
• Study Completion (Actual): July 29, 2019

Study Registration Dates

• First Submitted: January 29, 2016
• First Submitted That Met QC Criteria: February 1, 2016
• First Posted (Estimate): February 3, 2016

Study Record Updates

• Last Update Posted (Actual): July 20, 2021
• Last Update Submitted That Met QC Criteria: July 19, 2021
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: Plasma; Tetanus; Immunoglobulin; Td; Plasma Donor; Plasma Donation; Hyper-immunization
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Clostridium Infections; Corynebacterium Infections; Tetanus; Diphtheria
• Other Study ID Numbers: GB-0115

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes