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Trial registered on ANZCTR


Registration number
ACTRN12620001177943p
Ethics application status
Submitted, not yet approved
Date submitted
6/10/2020
Date registered
9/11/2020
Date last updated
9/11/2020
Date data sharing statement initially provided
9/11/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
A study to evaluate the safety and tolerability of Tetanus/Diptheria/Pertussis Booster Vaccine compared to a licensed Tdap vaccine in Healthy Volunteers between 10 - 22 years of age
Scientific title
A Phase 1 Randomized, Open Label, Active-Controlled, Dose Escalation, Multi-center Study to Evaluate the Safety, Tolerability, and Immunogenicity of an Investigational Tetanus/Diphtheria/Pertussis Booster Vaccine (Tdap-1018) Compared to a Licensed Tdap Vaccine in Healthy Volunteers Between 10 and 22 Years of Age
Secondary ID [1] 302447 0
DV2-TDAP-01
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pertussis 319269 0
Diptheria 319270 0
Tetanus 319271 0
Condition category
Condition code
Respiratory 317237 317237 0 0
Other respiratory disorders / diseases
Infection 317238 317238 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The study will be conducted in 2 parts:

• Part 1 will enroll healthy adult volunteers 18 to 22 years of age, inclusive. Part 1 will consist of approximately 24 subjects in 2 escalating dose levels of CpG(Tdap)-1018 (Group A: 1500 mcg; Group B: 3000 mcg) with approximately12 subjects in each group (Tdap 1018 n = 8; Boostrix n = 4).
• Part 2 will enroll healthy adolescent volunteers 10 to 17 years of age, inclusive. Part 2 will consist of approximately 250 subjects in 2 escalating dose levels of CpG(Tdap)-1018 (Group C: 1500 mcg; Group D: 3000 mcg) with approximately 125 subjects (Tdap 1018 n = 100; Boostrix n = 25) in each group.


All subjects will receive 1 dose of their assigned treatment (Tdap 1018 Dose 1, Tdap-1018 Dose 2, or Boostrix). All subjects will undergo assessments of safety and immunogenicity. Subjects will be followed for safety for 12 weeks after the study injection.
All subjects will have a pre-vaccination blood draw and receive the assigned treatment vaccine at Day 1. Blood draws for measuring post-vaccination antibody levels and exploratory evaluations will be done at Week 4. Safety assessments will be done at Weeks 4 and 12.
Intervention code [1] 318739 0
Treatment: Drugs
Comparator / control treatment
Active Comparator:
Boostrix: contains 5 Lf of tetanus toxoid, 2.5 Lf of diphtheria toxoid, 8 mcg of inactivated PT, 8 mcg of FHA, and 2.5 mcg of PRN adsorbed on 0.3 mg of aluminum hydroxide hydrate and 0.2 mg of aluminum phosphate.
Route of Administration: Intra Muscular
Control group
Active

Outcomes
Primary outcome [1] 325299 0
To evaluate the safety and tolerability of Tdap-1018. This is a composite outcome.
Timepoint [1] 325299 0

This is a composite primary outcome where each component is assessed by monitoring the following parameters through Week 12 or End of Study/Early Discontinuation.
Parameters:
1. Incidence of local and systemic post-injection reactions (PIRs)
2. Incidence of serious adverse events (SAEs)
3. Incidence of adverse events (AEs) leading to treatment discontinuation

PIRs, AEs and SAEs will be graded based on the United States Food and Drug Administration’s (FDA) Guidance for Industry: Center for Biologics Evaluation and Research (CBER) Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials.
Secondary outcome [1] 387441 0
To assess the immunogenicity to pertussis of Tdap-1018 compared with Boostrix 4 weeks after a booster vaccination
Timepoint [1] 387441 0
This is a composite secondary outcome. Each component is assessed by obtaining blood samples at the following timepoints: Day 1(prior to study vaccine injection), Day 4 and End of Study visit.
Parameters:
1. Geometric mean concentration (GMC) of antibodies to each of the pertussis antigens 4 weeks after dosing: anti-pertussis toxin (anti-PT), anti- filamentous hemagglutinin (anti-FHA), and anti-pertactin (anti-PRN).
2. Booster response rates for antibodies to pertussis antigens (inactivated pertussis toxin [PT], filamentous hemagglutinin [FHA], and pertactin [PRN]):
- In initially seronegative subjects (threshold to be defined), post-vaccination antibody concentrations greater than or equal to 4 × threshold.
- In initially seropositive subjects with pre-vaccination antibody concentrations between greater than or equal to threshold and 4 × threshold, an increase of greater than or equal to 4 × the pre-vaccination antibody concentration.
- In initially seropositive subjects with pre-vaccination antibody concentrations greater than 4 × threshold, an increase of greater than or equal to 2 × the pre-vaccination antibody concentration
- Ratio of GMCs of antibodies to pertussis antigens comparing Tdap 1018 with Boostrix.
- Geometric mean fold increase of anti-PT, anti-FHA, and anti-PRN (Day 29 versus Day 1)
Secondary outcome [2] 387442 0
To assess the immunogenicity to tetanus and diphtheria for Tdap-1018 compared with Boostrix 4 weeks after a booster vaccination
Timepoint [2] 387442 0
This is a composite secondary outcome. Each component is assessed by obtaining blood samples at the following timepoints: Day 1(prior to study vaccine injection), Day 4 and End of Study visit.
Parameters:
1. Booster response rates for anti-tetanus (anti-T) and anti-diphtheria (anti D) antibodies:
- In subjects with pre-vaccination less than 0.1 IU/mL, post-vaccination concentration greater than or equal to 0.4 IU/mL
- In subjects with pre-vaccination concentration greater than or equal to 0.1 IU/mL, an increase of at least 4 times the pre-vaccination concentration.

2. Percentage of subjects with (anti-T) antibodies greater than or equal to 0.1 IU/mL
3. Percentage of subjects with anti-T antibodies greater than or equal to 1.0 IU/mL
4. Percentage of subjects with (anti-D) antibodies greater than or equal to 0.1 IU/mL
5. Percentage of subjects with anti-D antibodies greater than or equal to 1.0 IU/mL
6. GMCs of anti-T and anti-D antibodies.

Eligibility
Key inclusion criteria
A subject must meet all of the following criteria to be eligible for enrollment (defined as receiving any study vaccine) in the study:
1) Willing to participate: pediatric assent and written parental/legal guardian consent; or adult informed consent provided for the study
2) Male or female, 18 to 22 (Part 1) or 10 to 17 (Part 2) years of age
3) Have documentation of 2 or more prior acellular pertussis (aP) vaccinations
4) Be in good health in the opinion of the investigator, based upon medical history, physical examination (adults), and laboratory evaluation (adults)
5) Adult subject, or adolescent subject and/or adult guardian of adolescent subject, be able to comprehend and follow all required study procedures and be available for all visits scheduled in the study
6) Seronegative for human immunodeficiency virus (HIV), adults only
Minimum age
10 Years
Maximum age
22 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
A subject with any 1 of the following criteria is not eligible for enrollment (defined as receiving any study vaccine) in the study:
1) Received acellular Tdap booster within the previous 3 years
2) History of diphtheria, tetanus or pertussis disease
3) History of encephalopathy within 7 days of a previous dose of pertussis vaccine
4) History of any progressive neurologic disorder, uncontrolled epilepsy, or progressive encephalopathy
5) If female of childbearing potential, is pregnant, breastfeeding, or planning a pregnancy
6) Known history of HIV (HIV 1/2 antibodies)
7) Has a history of sensitivity to any component of study vaccines
8) Has received any blood products or immunoglobulin within 90 days prior to study injection, or is likely to require infusion of blood products during the study period
9) Has received the following prior to the injection:
• 21 days: any inactivated virus vaccine
• 28 days:
- Any live virus vaccine
- Systemic corticosteroids (more than 3 consecutive days) or other immunomodulators or immune suppressive medication, with the exception of inhaled steroids
- Granulocyte or granulocyte-macrophage colony-stimulating factor
- Any other investigational medicinal agent
• 90 days: immunoglobulins or any blood products
• At any time: an injection of deoxyribonucleic acid plasmids or oligonucleotides
10) Is undergoing chemotherapy or expected to receive chemotherapy during the study period; has a diagnosis of cancer within the last 5 years other than squamous or basal cell carcinoma of the skin
11) History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
12) Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint(s)
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
10/11/2020
Actual
Date of last participant enrolment
Anticipated
2/07/2021
Actual
Date of last data collection
Anticipated
31/12/2021
Actual
Sample size
Target
274
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,WA,VIC
Recruitment hospital [1] 17737 0
The Children's Hospital at Westmead - Westmead
Recruitment hospital [2] 17739 0
Perth Children's Hospital - Nedlands
Recruitment hospital [3] 17755 0
The Royal Childrens Hospital - Parkville
Recruitment postcode(s) [1] 31593 0
2145 - Westmead
Recruitment postcode(s) [2] 31595 0
6009 - Nedlands
Recruitment postcode(s) [3] 31618 0
3052 - Parkville

Funding & Sponsors
Funding source category [1] 306876 0
Commercial sector/Industry
Name [1] 306876 0
Dynavax Technologies Corporation
Address [1] 306876 0
Dynavax Technologies Corporation
2100 Powell Street, Suite 900
Emeryville, CA 94608
U.S.A
Country [1] 306876 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Dynavax Technologies Corporation
Address
Dynavax Technologies Corporation
2100 Powell Street, Suite 900
Emeryville, CA 94608
U.S.A
Country
United States of America
Secondary sponsor category [1] 307430 0
Commercial sector/Industry
Name [1] 307430 0
Novotech (Australia) Pty Limited
Address [1] 307430 0
Novotech (Australia) Pty Limited
Level 3, 235 Pyrmont Street, Pyrmont NSW 2009, Australia
Country [1] 307430 0
Australia

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 307032 0
Bellberry Limited HREC
Ethics committee address [1] 307032 0
Bellberry Ltd 123 Glen Osmond Rd, Eastwood, SA 5063
Ethics committee country [1] 307032 0
Australia
Date submitted for ethics approval [1] 307032 0
23/09/2020
Approval date [1] 307032 0
Ethics approval number [1] 307032 0

Summary
Brief summary
The purpose of the study is to determine what dose of Tdap-1018, a vaccine intended for active booster immunization against tetanus, diphtheria, and pertussis in individuals 10 to 22 years of age is safe for use.

Who is it for?
You may be eligible for this study if you are a healthy volunteer aged between 10 and 22 years.

Study details:
The study will be conducted in 2 parts:
• Part 1 will enroll healthy adult volunteers 18 to 22 years of age, inclusive. Part 1 will consist of approximately 24 subjects in 2 dose levels of CpG(Tdap)-1018 (Group A: Tdap-1018 Dose 1; Group B: Tdap-1018 Dose 2) with approximately 12 subjects in each group (Tdap 1018 n = 8; Boostrix n = 4).
• Part 2 will enroll healthy adolescent volunteers 10 to 17 years of age, inclusive. Part 2 will consist of approximately 250 subjects in 2 dose levels of CpG(Tdap)-1018 (Group C: Tdap-1018 Dose 1; Group D: Tdap-1018 Dose 2) with approximately 125 subjects (Tdap 1018 n = 100; Boostrix n = 25) in each group.
All subjects will receive 1 dose of their assigned treatment (Tdap 1018 Dose 1, Tdap-1018 Dose 2, or Boostrix). All subjects will undergo assessments of safety and immunogenicity. Subjects will be followed for safety for 12 weeks after the study injection.
All subjects will have a pre-vaccination blood draw and receive the assigned treatment vaccine at Day 1. Blood draws for measuring post-vaccination antibody levels and exploratory evaluations will be done at Week 4. Safety assessments will be done at Weeks 4 and 12.

It is hoped that this study will determine the safest and most effective dose of Tdap-1018 vaccine intended for active booster immunization against tetanus, diphtheria, and pertussis.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 105794 0
A/Prof Nicholas Wood
Address 105794 0
Westmead Children’s Hospital,
Corner Hawkesbury Road and Hainsworth Street,
Westmead, NSW 2145
Country 105794 0
Australia
Phone 105794 0
+61 2 9845 1429
Fax 105794 0
Email 105794 0
nicholas.wood@sydney.edu.au
Contact person for public queries
Name 105795 0
Ms Kim Erby
Address 105795 0
Associate Director, Medical Affairs,
Dynavax
2100 Powell Street, Suite 900
Emeryville, CA 94608
Country 105795 0
United States of America
Phone 105795 0
+15106650466
Fax 105795 0
Email 105795 0
kerby@dynavax.com
Contact person for scientific queries
Name 105796 0
Dr Randall N. Hyer
Address 105796 0
MD, Vice President, Clinical Development and Medical Affairs
2100 Powell Street, Suite 900
Emeryville, CA 94608

Country 105796 0
United States of America
Phone 105796 0
+15106650451
Fax 105796 0
Email 105796 0
rhyer@dynavax.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
The sponsor typically provides aggregate subject data only and do not publish individual data because of the following rationale: All analyses and conclusions for the study are based on a summary of the study-level aggregate data and not the subject-level.
What supporting documents are/will be available?
No other documents available
Summary results
No Results