Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12620001177943
Ethics application status
Approved
Date submitted
6/10/2020
Date registered
9/11/2020
Date last updated
15/04/2024
Date data sharing statement initially provided
9/11/2020
Date results information initially provided
9/09/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
A study to evaluate the Safety, Tolerability, and Immunogenicity of an Investigational Tetanus/Diphtheria/Pertussis Booster Vaccine (Tdap-1018) Compared to Boostrix in Healthy Volunteers Between 10 and 22 Years of Age
Scientific title
A Phase 1 Randomized, Participant-Blinded, 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 Boostrix 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 approximately 90 healthy adult volunteers 18 to 22 years of age, inclusive in two escalating dose levels of Tdap-1018. 45 participants will be enrolled into each of the groups:
- Group A (Tdap 1018, 1500mcg n=30; Boostrix n=15)
- Group B (Tdap-1018, 3000 mcg n=30; Boostrix n=15)
• Part 2 will enroll healthy adolescent volunteers 10 to 17 years of age, inclusive. Part 2 will consist of approximately 48 participants in 2 escalating dose levels of Tdap-1018 (Group C: 1500 mcg; Group D: 3000 mcg) with approximately 24 participants (Tdap 1018 n = 16; Boostrix n = 8) in each group.

A Safety Monitoring Committee (SMC) will oversee the dose escalation. Enrollment of adolescent participants will be initiated after 12 vaccine recipients in Part 1, Group B have completed week 4 and a preliminary safety assessment is completed by the SMC.

All adult and adolescent participants will receive 1 dose of their assigned treatment. All participants will undergo assessments of safety and immunogenicity. Participants will be followed for safety for 12 weeks after the study injection.
All participants 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 primary outcome where each component is assessed by monitoring the following 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.
In clinical monitoring will be done for 48 hours for any adverse events, after that telephonic follow up will be done. These will be monitored through telephone follow-up, participant self-report via online or paper diary and in-center clinical monitoring by study nurse.
Timepoint [1] 325299 0
The primary outcome parameters like AEs, SAEs will be monitored through Day 1 to week 12 or End of Study/Early Discontinuation.
Assessment of PIRs will be collected for a minimum of 30 minutes following the study injection at the clinical site , and during the 7-day (Days 1-7) follow-up period after vaccination.
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:
1) Geometric mean concentration (GMC) of antibodies to each of the pertussis antigens:
anti-pertussis toxin (anti-PT), anti- filamentous hemagglutinin (anti-FHA), and anti-pertactin (anti-PRN) at Day 1 and Day 29 (Week 4).
2) Booster response rates for antibodies to pertussis antigens (inactivated pertussis toxin [PT], filamentous hemagglutinin [FHA], and pertactin [PRN]) at Day 1 and Day 29 (Week 4).
3) Ratio of GMCs of antibodies to pertussis antigens comparing Tdap 1018 with Boostrix at Day 1 and Day 29 (Week 4).
4. Geometric mean fold increase of anti-PT, anti-FHA, and anti-PRN at Day 1 and Day 29 (Week 4).
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 for corresponding parameters at the following timepoints:
1) Booster response rates for anti-tetanus (anti-T) and anti-diphtheria (anti D) antibodies at Day 1 and Day 29.
2) Percentage of participants with (anti-T) antibodies greater than or equal to 0.1 IU/mL at Day 1 and Day 29.
3) Percentage of participants with anti-T antibodies greater than or equal to 1.0 IU/mL at Day 1 and Day 29.
4) Percentage of participants with (anti-D) antibodies greater than or equal to 0.1 IU/mL at Day 1 and Day 29.
5) Percentage of participants with anti-D antibodies greater than or equal to 1.0 IU/mL at Day 1 and Day 29.
6) GMCs of anti-T and anti-D antibodies at Day 1 and Day 29.

Eligibility
Key inclusion criteria
A participant 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 participant, or adolescent participant and/or adult guardian of adolescent participant, 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
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
A participant 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:
• 14 days: any non-live virus vaccine
• 28 days:
- Any live virus vaccine, including a COVID-19 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 including COVID-19 vaccine
• 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
13) Requires vaccination for travel or medical reasons (eg, potential exposure to one of the diseases, prophylaxis for exposure to vulnerable people, babies)
14) History of autoimmune disease.

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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


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

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
10/11/2020
Actual
27/01/2021
Date of last participant enrolment
Anticipated
31/05/2022
Actual
26/05/2022
Date of last data collection
Anticipated
30/06/2022
Actual
25/08/2022
Sample size
Target
138
Accrual to date
Final
117
Recruitment in Australia
Recruitment state(s)
ACT,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 hospital [4] 22382 0
Paratus Clinical Pty Ltd Blacktown Trial Clinic - Blacktown
Recruitment hospital [5] 22383 0
Northern Beaches Clinical Research - Brookvale
Recruitment hospital [6] 22384 0
Paratus Clinical Research - Ochre Health Medical Centre Bruce - Bruce
Recruitment hospital [7] 22385 0
Paratus Clinical Pty Ltd Kanwal Trial Clinic - Kanwal
Recruitment postcode(s) [1] 31593 0
2145 - Westmead
Recruitment postcode(s) [2] 31595 0
6009 - Nedlands
Recruitment postcode(s) [3] 31618 0
3052 - Parkville
Recruitment postcode(s) [4] 37546 0
2148 - Blacktown
Recruitment postcode(s) [5] 37547 0
2100 - Brookvale
Recruitment postcode(s) [6] 37548 0
2617 - Bruce
Recruitment postcode(s) [7] 37549 0
2259 - Kanwal

Funding & Sponsors
Funding source category [1] 306876 0
Commercial sector/Industry
Name [1] 306876 0
Dynavax Technologies Corporation
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
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
08/12/2020
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 booster immunization against tetanus, diphtheria, and pertussis in individuals 10 to 22 years of age is optimum for use.
The study will enroll healthy adolescent and adult volunteers aged between 10 and 22 years. The total duration of the study will be approximately 16 weeks.
Study details:
The study will be conducted in 2 parts:
• Part 1 will enroll approximately 90 healthy adult participants 18 to 22 years of age, inclusive. Part 1 has two groups evaluating two dose levels of Tdap-1018.
• Part 2 will enroll approximately 48 healthy adolescent participants 10 to 17 years of age, inclusive. Part 2 will also have two groups for evaluating two dose levels of Dtap-1018.
All participants will receive 1 dose of their assigned treatment (Tdap 1018 Dose 1, Tdap-1018 Dose 2, or Boostrix). All participants will undergo assessments of safety and immunogenicity. Participants will be followed for safety for 12 weeks after the study injection.
All participants 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 perhaps intended that this study will determine the 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
[email protected]
Contact person for public queries
Name 105795 0
Ms Tammy Boyce
Address 105795 0
Sr. Director, Clinical Operations
Address: Dynavax 2100 Powell Street, Suite 900 Emeryville, CA 94608
Country 105795 0
United States of America
Phone 105795 0
+1 6199337176
Fax 105795 0
Email 105795 0
[email protected]
Contact person for scientific queries
Name 105796 0
Dr Robert Janssen
Address 105796 0
Senior Vice President, Clinical development Medical & Regulatory Affairs
Address: Dynavax, 2100 Powell Street, Suite 900 Emeryville, CA 94608
Country 105796 0
United States of America
Phone 105796 0
+1 510 665 0414
Fax 105796 0
Email 105796 0
[email protected]

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 Supporting Document Provided



Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Basic resultsNo 380684-(Uploaded-09-02-2024-16-38-34)-Basic results summary.pdf
Plain language summaryNo Whooping cough is a severe respiratory tract infec... [More Details]

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseNovel approaches to reactivate pertussis immunity.2022https://dx.doi.org/10.1080/14760584.2022.2149499
N.B. These documents automatically identified may not have been verified by the study sponsor.