A study to evaluate the safety and effects on the immune system of a tetanus and diphtheria vaccine which does not need any cold chain distribution or storage

ISRCTN	ISRCTN98920861
DOI	https://doi.org/10.1186/ISRCTN98920861
Integrated Research Application System (IRAS)	1009178
Protocol serial number	SPL-SPVX02-01
Sponsor	Stablepharma Ltd
Funder	Stablepharma Ltd

Submission date: 25/12/2024
Registration date: 09/01/2026
Last edited: 09/01/2026

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Infections and Infestations

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Background and study aims
Stablepharma is developing a thermostable lyophilized tetanus and diphtheria (Td) vaccine (SPVX02) based on a reformulation of Tetadif® vaccine. This study aims to evaluate the safety, immunogenicity and tolerability of SPVX02 whilst also providing comparative immunogenicity data with Tetadif® and diTeBooster® (comparator investigational medicinal products). The study aims to demonstrate that SPVX02, Tetadif and diTeBooster generate comparable anti-tetanus and anti-diphtheria post-boost immune responses in healthy adults.

Who can participate?
Healthy participants (aged 18-55 years) who have previously received a primary vaccination against tetanus and diphtheria but who have not received a booster vaccination in the last 10 years.

What does the study involve?
Participants will be randomly allocated to receive a single vaccination of either SPVX02, Tetadif or diTeBooster. On Day 1, an electronic diary, tape measure and thermometer will be provided to perform self-assessments of local and systemic safety and tolerability up to, and including, Day 7. All participants will have a follow-up telephone call on Day 2 and return to the clinic for study assessments on Days 7 and 28. End of study visit procedures will be performed at the final clinic visit on Day 28.

What are the possible benefits and risks of participating?
Risks include local and systemic reactions such as pain, redness, swelling at the injection site, fever, fatigue, headache, or more serious reactions (allergic or anaphylactic reactions). To mitigate this, participants will be closely monitored for at least 30 minutes post-vaccination.

Where is the study run from?
Stablepharma Ltd (UK)

When is the study starting and how long is it expected to run for?
December 2024 to July 2025

Who is funding the study?
Stablepharma Ltd (UK)

Who is the main contact?

Contact information

Dr Karen O'Hanlon
Scientific

90 Victoria Street
Bristol
BA1 1HE
United Kingdom

Phone	+44 (0)7812606184
Email	kohanlon@stablepharma.com

Prof Saul Faust
Principal investigator

NIHR Southampton Clinical Research Facility
Southampton General Hospital
Tremona Road
Southampton
SO16 6YD
United Kingdom

Phone	+44 (0)238 1204989
Email	s.faust@soton.ac.uk

Study information

Primary study design	Interventional
Study design	Single-blind randomized controlled parallel-group trial
Secondary study design	Randomised controlled trial
Scientific title	A Phase I, randomised, single-blind clinical study to evaluate the safety, immunogenicity and tolerability of SPVX02, a tetanus and diphtheria booster vaccine, against two comparator vaccines in healthy adult participants
Study objectives	Primary objectives: 1. Evaluate the safety of a single vaccination of SPVX02 2. Evaluate the tolerability of a single vaccination of SPVX02, Tetadif® or diTeBooster® Secondary objectives: 1. To evaluate the seroprotection rates observed in sera collected from participants on Day 28 post-dose, following administration of a single dose of SPVX02, Tetadif® or diTeBooster® 2. To evaluate the post-vaccination Geometric Mean Titers (GMT) of anti-TT antibodies and anti-DT antibodies observed in sera collected from participants at Day 28 post-dose, following administration of a single dose of SPVX02, Tetadif® or diTeBooster® 3. To evaluate the longer-term seroprotection rates observed in sera collected from participants on Day 28 post-dose, following administration of a single dose of SPVX02, Tetadif® or diTeBooster®
Ethics approval(s)	Approved 12/02/2025, London Bridge REC (Redman Place, London, E20 1JQ, United Kingdom; +44 (0)207 104 8229, +44 (0)207 104 8140, +44 (0)207 104 8055; londonbridge.rec@hra.nhs.uk), ref: 25/LO/0059
Health condition(s) or problem(s) studied	Prevention of tetanus and diphtheria infection in healthy volunteers
Intervention	The study will be conducted in 60 healthy participants who have previously received a primary vaccination against tetanus and diphtheria but who have not received a booster vaccination in the last 10 years. Three treatment groups of 20 participants will be randomised 1:1:1 using a paper-based randomisation process in a single-blind manner to receive a single dose of SPVX02, Tetadif® or diTeBooster®. All treatment groups will be dosed in parallel, and all participants will be followed up for 28 days post-vaccination.
Intervention type	Biological/Vaccine
Phase	Phase I
Drug / device / biological / vaccine name(s)	SPVX02 , Tetadif, diTeBooster
Primary outcome measure(s)	Incidence of safety and reactogenicity events, which include adverse events , serious adverse events, and the incidence of local and systemic reactogenicity events observed for 7 days post-dose which include: pain, induration, tenderness, swelling, warmth, erythema at the vaccination site plus feverishness, chills, myalgia, fatigue, headache, arthralgia, rash measured using data collected from electronic Case Report Forms (eCRF) at one time point
Key secondary outcome measure(s)	Incidence of seroprotection resulting from a single dose of SPVX02, Tetadif® or diTeBooster®; seroprotection is defined as an IgG serum antibody titre ≥0.1 IU/mL, which is the antibody titre level of anti-TT and anti-DT antibodies that are considered to confer protection against diphtheria and tetanus infection, measured using enzyme linked immunosorbent assays (ELISAs) at 28 days post-dose Evaluation of geometric mean titers (GMTs) of anti-TT and anti-DT antibodies resulting from a single dose of SPVX02, Tetadif® or diTeBooster® measured using enzyme linked immunosorbent assays (ELISAs) at 28 days post-dose Incidence of longer-term seroprotection resulting from a single dose of SPVX02, Tetadif® or diTeBooster®; longer-term seroprotection is defined as an antibody titre ≥1.0 IU/mL, which is the antibody titre level of anti-TT and anti-DT antibodies that are considered to confer longer-term protection against diphtheria and tetanus infection, measured using enzyme linked immunosorbent assays (ELISAs) at 28 days post-dose
Completion date	28/09/2025

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Upper age limit	55 Years
Sex	All
Target sample size at registration	60
Total final enrolment	60
Key inclusion criteria	1. Participant is 18-55 years of age at the time of screening with a BMI ≤30 kg/m2 2. Participant is able to provide informed consent indicating that they are willing to participate and that they understand the purpose of the study and the assessments they are required to undergo as part of their involvement in the study 3. Participant is considered to be in good health with no current conditions that may significantly impair participant safety or influence the study results, as determined by the Investigator 4. Participant does not have any medical condition that causes primary or secondary immunodeficiency 5. Participant confirms (via GP records, NHS mobile phone application, or similar) that they have previously received primary or booster immunisation with previous diphtheria and tetanus vaccines 6. Participants who were born female and are of child-bearing potential must be practicing an acceptable effective method of contraception for the duration of the study. Acceptable methods for this study include: 6.1. Hormonal contraception (use of hormonal contraception should start at least 28 days before the first administration of the study vaccine) 6.2. Intrauterine device (IUD) 6.3. Intrauterine hormone-releasing system (IUS) 6.4. Male or female condom with or without spermicide 6.5. Cap, diaphragm or sponge with a vaginal spermicide 6.6. Vasectomised partner (the vasectomised partner should be the sole partner for that volunteer) 6.7. Sexual abstinence (sexual abstinence is considered an effective method only if defined as refraining from heterosexual intercourse from signing the ICF until the end of the study) 7. Participants who were born female and are not of child-bearing potential must be: 7.1. Postmenopausal: amenorrhea (no menstrual periods) for at least 12 months without alternative medical cause. 7.2. Permanently sterile: permanent sterilization methods include hysterectomy (removal of the womb), bilateral salpingectomy (surgical removal of the fallopian tubes), bilateral tubal occlusion/ligation procedures, and bilateral oophorectomy (surgical removal of both ovaries). 8. Male participants must be willing to use a contraception method upon enrolment, during the course of the study, and for 1 month post-dose.
Key exclusion criteria	1. Serious and uncontrolled chronic disease (i.e., cardiac, pulmonary, renal, neurologic, metabolic, rheumatologic, etc) 2. Known or suspected autoimmune disease or impairment of immunological function of any cause 3. Acute medical illness, with or without fever, or an oral or tympanic temperature >38°C within the 72 hours prior to dosing. 4. Administration of immunoglobulin or other blood products within the last three months prior to screening; administration of corticosteroids (injected or oral) or other immunomodulatory therapy within 42 days prior to Day 1 5. A positive test result at screening for HIV, hepatitis C virus or hepatitis B virus 6. Received any vaccine in the 30 days prior to screening or planning to receive a vaccine in the 30 days following administration of the study vaccine 7. History of allergic disease or any suspected or known hypersensitivity to any of the SPVX02, Tetadif® or diTeBooster® components 8. Any history of anaphylaxis in reaction to a vaccination 9. Unable to attend scheduled visits or unable to comply with the study procedures 10. Enrolled in another interventional clinical study or has participated in an interventional clinical study in the last 6 months prior to Day 1. 11. Any condition that would pose a health risk to the participant or interfere with the evaluation of either vaccine in the opinion of the Investigator 12. Female and of childbearing potential who does not agree either to remain abstinent or to use effective birth control during the period of the study 13. Intending to become pregnant or breastfeeding during the period of the study. 14. A history of Guillain-Barré syndrome 15. Receipt of a tetanus or diphtheria vaccination within the 10 years prior to enrolment 16. A previous history of diphtheria or tetanus disease within the last 25 years 17. History of Arthus-type hypersensitivity reaction. 18. History of alcohol or substance abuse. 19. Unable to fulfil all the requirements of the study in the opinion of the Investigator. 20. Significant psychiatric history in the last 2 years. 21. Presence of permanent body art on both right and left upper arms that would obstruct the ability to observe local reactions at the injection site 22. Any other finding that, in the opinion of the Investigator or Sponsor, deems the subject unsuitable for the study
Date of first enrolment	17/02/2025
Date of final enrolment	26/08/2025

Locations

Countries of recruitment

United Kingdom
England

Study participating centres

NIHR Southampton Clinical Research Facility

Southampton General Hospital
Tremona Road
Southampton
SO16 6YD
England

Medicines Evaluation Unit Limited

The Langley Building
Southmoor Road
Wythenshawe
Manchester
M23 9QZ
England

Queen Alexandra Hospital

Southwick Hill Road
Cosham
Portsmouth
PO6 3LY
England

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Data sharing statement to be made available at a later date
IPD sharing plan

Editorial Notes

26/02/2025: ISRCTN received notification of combined HRA/MHRA approval for this trial on 26/02/2025.
27/12/2024: Study's existence confirmed by the HRA.