InvaplexAR-Detox and DmLT Adjuvant in the Netherlands and Zambia

NCT ID: NCT05961059

Last Updated: 2024-11-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

85 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-10-10

Study Completion Date

2025-05-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

The goal of this clinical trial is to test a new Shigella vaccine (InvaplexAR-DETOX) in combination with a new adjuvant (dmLT) in healthy participants. The main questions it aims to answer are:

* Is the new Shigella vaccine (with and without the new adjuvant) safe and well tolerated?
* How wel does the new Shigella vaccine stimulate the immune system in combination with the new adjuvant, and without the new adjuvant?

Participants will receive three vaccinations at 28-day intervals. Researchers will compare the results of participants vaccinated with the vaccine in combination with the adjuvant to the results of participants vaccinated with the vaccine only and to the results of participants vaccinated with a placebo (fake vaccine).

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Rationale: Shigella remains endemic in many places and occurs in epidemics that cause considerable morbidity and mortality. Vaccines are an attractive and potentially highly cost-effective tool for the prevention of shigellosis and can fill current gaps in effective prevention strategies. A challenge to effective Shigella vaccine development has been the reduced immunogenicity and protective efficacy of candidate Shigella vaccines in infants and children less than 3 years of age. The potential impact of including an adjuvant in candidate parenteral Shigella vaccine formulations needs to be evaluated. InvaplexAR-Detox is an injectable Shigella vaccine that uses a novel combination of conserved invasion plasmid antigen proteins with a serotype-specific bacterial lipopolysaccharide attenuated for safe intramuscular administration. The adjuvant dmLT has been shown to significantly enhance Shigella immune responses in mice and has safely been administered intramuscularly in healthy volunteers in combination with other antigens in phase I trials.

Objective: to evaluate the safety and immunogenicity of two strength formulations of a candidate Shigella vaccine (2.5 or 10 μg Sfl2a InvaplexAR-Detox) given with and without adjuvant (0.1 μg dmLT).

Study design: this is a phase Ia/b dose escalation, randomized, double-blind, placebo-controlled trial assessing the safety, tolerability and immunogenicity of three vaccinations given 4 weeks apart of Sfl2a InvaplexAR-Detox vaccine alone or in combination with the dmLT adjuvant in the Leiden University Medical Center in the Netherlands and at the Centre for Infectious Disease Research in Zambia (CIDRZ). The study will be initiated with the low vaccine dose in the Netherlands (Cohort A) and will not proceed to the high vaccine dose in the Netherlands (Cohort B) before the safety data of Cohort A has been reviewed by the Safety Monitoring Committe (SMC). The SMC will also review the safety data of Cohort B before the high vaccine dose will be administered in Zambian adults (Cohort C).

Study population: a total of 50 healthy Dutch and 35 healthy Zambian adults aged 18-50 years.

Intervention: a 2.5 μg or 10 μg intramuscular dose of the candidate Shigella vaccine Sfl2a InvaplexAR-Detox given with and without double mutant (LT R192G/L211A) enterotoxigenic Escherichia coli heat labile toxin adjuvant (0.1 μg dmLT) given at day 1, day 29 and day 57 compared to a placebo (saline).

Main study endpoints: Primary endpoint measures are the occurrence of solicited and unsolicited adverse events considered to be related to vaccination. Secondary outcome measures are humoral and cellular immune responses to vaccination with and without adjuvant compared to placebo.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Shigellosis Bacillary Dysentery

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

A phase Ia/b dose escalation, randomized, double-blind, placebo-controlled clinical trial
Primary Study Purpose

PREVENTION

Blinding Strategy

TRIPLE

Participants Caregivers Investigators
Double blind

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

A1 - Low dose vaccine (Netherlands)

10 Dutch participants who receive three 2.5 μg doses of the vaccine without adjuvant at a 28-day interval in Cohort A.

Group Type EXPERIMENTAL

2.5 μg InvaplexAR-Detox

Intervention Type BIOLOGICAL

2.5 μg intramuscular dose of Sfl2a InvaplexAR-Detox.

A2 - Low dose vaccine + adjuvant (Netherlands)

10 Dutch participants who receive three 2.5 μg dose of the vaccine with 0.1 μg of adjuvant at a 28-day interval in Cohort A.

Group Type EXPERIMENTAL

2.5 μg InvaplexAR-Detox

Intervention Type BIOLOGICAL

2.5 μg intramuscular dose of Sfl2a InvaplexAR-Detox.

0.1 μg of dmLT

Intervention Type BIOLOGICAL

0.1 μg intramuscular dose of double mutant (LT R192G/L211A) enterotoxigenic Escherichia coli heat labile toxin (dmLT).

B1/C1 - High dose vaccine (Netherlands & Zambia)

10 Dutch participants who receive three 10 μg vaccine doses without adjuvant at a 28-day interval in Cohort B and 15 Zambian participants who receive three 10 μg vaccine doses without adjuvant at a 28-day interval in Cohort C.

Group Type EXPERIMENTAL

10 μg InvaplexAR-Detox

Intervention Type BIOLOGICAL

10 μg intramuscular dose of Sfl2a InvaplexAR-Detox.

B2/C2 - High dose vaccine + adjuvant (Netherlands & Zambia)

10 Dutch participants that receive three 10 μg vaccine doses with 0.1 μg of adjuvant at a 28-day interval in Cohort B and 15 Zambian participants that receive three 10 μg vaccine doses with 0.1 μg of adjuvant at a 28-day interval in Cohort C.

Group Type EXPERIMENTAL

10 μg InvaplexAR-Detox

Intervention Type BIOLOGICAL

10 μg intramuscular dose of Sfl2a InvaplexAR-Detox.

0.1 μg of dmLT

Intervention Type BIOLOGICAL

0.1 μg intramuscular dose of double mutant (LT R192G/L211A) enterotoxigenic Escherichia coli heat labile toxin (dmLT).

A3/B3/C3 - Placebo (Netherlands & Zambia)

5 Dutch participants who receive three placebo vaccinations at a 28-day interval in Cohort A, another 5 Dutch participants who receive three placebo vaccinations at a 28-day interval in Cohort B and 5 Zambian participants who receive three placebo vaccinations at a 28-day interval in Cohort C.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type BIOLOGICAL

Placebo vaccination with commercially available saline solution.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

2.5 μg InvaplexAR-Detox

2.5 μg intramuscular dose of Sfl2a InvaplexAR-Detox.

Intervention Type BIOLOGICAL

10 μg InvaplexAR-Detox

10 μg intramuscular dose of Sfl2a InvaplexAR-Detox.

Intervention Type BIOLOGICAL

0.1 μg of dmLT

0.1 μg intramuscular dose of double mutant (LT R192G/L211A) enterotoxigenic Escherichia coli heat labile toxin (dmLT).

Intervention Type BIOLOGICAL

Placebo

Placebo vaccination with commercially available saline solution.

Intervention Type BIOLOGICAL

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

1. Healthy adult, male or female, aged 18 to 50 years (inclusive) at the time of inclusion (=vaccination).
2. Provide written informed consent before initiation of any study procedures.
3. Available to complete all study visits and procedures.
4. Negative stool PCR test for Shigella.
5. Women of childbearing potential: negative pregnancy test at screening and before each study vaccine administration. Women are considered not of childbearing potential if they are postmenopausal (no menses for 12 months without an alternative medical cause), or if they have no uterus or no ovaries. Women of childbearing potential must agree to use continuous adequate contraception to avoid pregnancy during the study, for at least 4 weeks before the first vaccination and for 3 months following the last vaccine dose.

Adequate methods of contraception for this study include:

1\. hormonal contraception

1. combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, or transdermal)
2. progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, or implantable) 2. intrauterine device (IUD) 3. intrauterine hormone-releasing system (IUS) 4. bilateral tubal occlusion/litigation procedure 5. vasectomized partner (the vasectomized partner should be the sole male sexual partner for that participant).

6\. sexual abstinence (defined as refraining from heterosexual intercourse from signing the informed consent until 3 months after the last vaccine dose).
1. Any history or evidence of clinically relevant chronic medical conditions (such as: psychiatric conditions, diabetes mellitus, hypertension \[treated by medication\], autoimmune disorders, immunodeficiencies, cardiovascular, renal disease or inflammatory bowel disease). Trial physicians (in consultation with the principal investigator) will use clinical judgement on a case-by-case basis to assess safety risks under this criterion.
2. Current use of immunosuppressive medications (except for antihistamines and topical or inhalation corticosteroids).
3. Women who are a) currently nursing or b) who are pregnant or planning to become pregnant during the study period plus 3 months beyond the last vaccine dose.
4. Participation in research involving another investigational product (defined as receipt of an investigational product or exposure to an invasive investigational device) 30 days before the first vaccination or anytime through the last in-clinic study safety visit.
5. Positive blood test for hepatitis B surface antigen (HbsAg), hepatitis C virus (HCV), or human immunodeficiency virus (HIV).
6. Clinically significant abnormalities on basic laboratory screening tests.
7. Systemic antimicrobial treatment (i.e., topical treatments are not an exclusion criterion) within 1 week before the first vaccine dose (temporary exclusion).
8. Known hypersensitivity to compounds in the vaccine or adjuvant or other known drug allergies that may increase the risk of adverse events.
9. Regular use (weekly or more often) of antidiarrheal, anti-constipation, or antacid therapy.
10. Abnormal stool pattern (fewer than 3 stools per week or more than 3 stools per day) on a regular basis; loose or liquid stools on other than an occasional basis.
11. Personal or family history of inflammatory arthritis.
12. Proven allergy to any substance in the InvaplexAR-Detox vaccine or dmLT or history of anaphylactic reaction to any other vaccine.
13. Exclusionary skin disease history/findings that would confound assessment or prevent appropriate monitoring of local AEs, or possibly increase the risk of local AEs.
14. Recent (\<3 months) history of gastroenteritis.
15. Received previous licensed or experimental Shigella vaccine, dmLT or live Shigella challenge.
16. Any severe medical condition that might place the participant at increased risk of adverse events according to the clinical judgment of the study clinicians in consultation with the PI.
17. Any planned vaccination within 14 days before the first vaccine dose until the last in-clinic study visit, with the exception of SARS-CoV-2 vaccines or influenza vaccines.
Minimum Eligible Age

18 Years

Maximum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Centre for Infectious Disease Research in Zambia

OTHER

Sponsor Role collaborator

PATH

OTHER

Sponsor Role collaborator

Walter Reed Army Institute of Research (WRAIR)

FED

Sponsor Role collaborator

Göteborg University

OTHER

Sponsor Role collaborator

European Vaccine Initiative

OTHER

Sponsor Role collaborator

European and Developing Countries Clinical Trials Partnership (EDCTP)

OTHER_GOV

Sponsor Role collaborator

Leiden University Medical Center

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Meta Roestenberg

Priniciple Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Leiden University Medical Center

Leiden, , Netherlands

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

Netherlands

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Meta Roestenberg, MD, PhD

Role: CONTACT

+3171715262613

Maxim Bax, MD

Role: CONTACT

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

M. Roestenberg, MD. PhD.

Role: primary

+3171715262613

M. Roestenberg, MD. PhD.

Role: backup

References

Explore related publications, articles, or registry entries linked to this study.

Roozen GVT, Sukwa N, Chirwa M, White JA, Estrada M, Maier N, Turbyfill KR, Laird RM, Suvarnapunya AE, Sayeh A, D'Alessio F, Marion C, Pattacini L, Hoogerwerf MA, Murugan R, Terrinoni M, Holmgren JR, Sirima SB, Houard S, Simuyandi M, Roestenberg M. Safety, Tolerability, and Immunogenicity of the InvaplexAR-DetoxShigella Vaccine Co-Administered with the dmLT Adjuvant in Dutch and Zambian Adults: Study Protocol for a Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Phase Ia/b Clinical Trial. Vaccines (Basel). 2025 Jan 8;13(1):48. doi: 10.3390/vaccines13010048.

Reference Type DERIVED
PMID: 39852827 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

SUNSHINE

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Zinc Supplementation in Shigella Patients
NCT00321126 COMPLETED PHASE3
Praziquantel in Children Under Age 4
NCT03640377 UNKNOWN PHASE2