ShigellosisPhase 1SUNSHINENCT05961059
InvaplexAR-Detox and DmLT Adjuvant in the Netherlands and Zambia
A Phase 1 study testing 2.5 μg InvaplexAR-Detox, 10 μg InvaplexAR-Detox and 0.1 μg of dmLT in people with Shigellosis and Bacillary Dysentery, run by Leiden University Medical Center at 1 site in Netherlands.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Shigellosis, Bacillary Dysentery
- What is being tested?
- 2.5 μg InvaplexAR-Detox, 10 μg InvaplexAR-Detox and 0.1 μg of dmLT
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 85 participants
- Where
- 1 siteNetherlands
- Study dates
- 10 Oct 2024to May 2025
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy adult, male or female, aged 18 to 50 years (inclusive) at the time of inclusion (=vaccination).
- Provide written informed consent before initiation of any study procedures.
- Available to complete all study visits and procedures.
- Negative stool PCR test for Shigella.
- 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:
Show all 27Show fewer
- 1. hormonal contraception
- combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, or transdermal)
- 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).
- 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.
- Current use of immunosuppressive medications (except for antihistamines and topical or inhalation corticosteroids).
- 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.
- 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.
- Positive blood test for hepatitis B surface antigen (HbsAg), hepatitis C virus (HCV), or human immunodeficiency virus (HIV).
- Clinically significant abnormalities on basic laboratory screening tests.
- Systemic antimicrobial treatment (i.e., topical treatments are not an exclusion criterion) within 1 week before the first vaccine dose (temporary exclusion).
- Known hypersensitivity to compounds in the vaccine or adjuvant or other known drug allergies that may increase the risk of adverse events.
- Regular use (weekly or more often) of antidiarrheal, anti-constipation, or antacid therapy.
- 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.
- Personal or family history of inflammatory arthritis.
- Proven allergy to any substance in the InvaplexAR-Detox vaccine or dmLT or history of anaphylactic reaction to any other vaccine.
- Exclusionary skin disease history/findings that would confound assessment or prevent appropriate monitoring of local AEs, or possibly increase the risk of local AEs.
- Recent (<3 months) history of gastroenteritis.
- Received previous licensed or experimental Shigella vaccine, dmLT or live Shigella challenge.
- 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.
- 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.
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Maxim Bax, MD contact
Netherlands1 site, 1 recruiting
- Recruiting
Leiden University Medical Center
Leiden, 2333 ZA
M. Roestenberg, MD. PhD., +3171715262613, m.roestenberg@lumc.nl
M. Roestenberg, MD. PhD.
About this study
Official title: Phase Ia/b Double-blind, Placebo-controlled, Dose Escalating Safety Study of Detoxified Shigella Flexneri 2a Artificial Invasin Complex (InvaplexAR-Detox) Vaccine Formulated with and Without DmLT Adjuvant Given Intramuscularly to Healthy Adults in the Netherlands and Zambia
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).
Read the detailed description
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
- Shigellosis, Bacillary Dysentery
- Being tested
- 2.5 μg InvaplexAR-Detox, 10 μg InvaplexAR-Detox, 0.1 μg of dmLT, Placebo
- Keywords
- Vaccine, Invaplex, dmLT, Shigella
- Medical subject headings
- Dysentery, Bacillary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
2.5 μg InvaplexAR-DetoxBiological
2.5 μg intramuscular dose of Sfl2a InvaplexAR-Detox.
10 μg InvaplexAR-DetoxBiological
10 μg intramuscular dose of Sfl2a InvaplexAR-Detox.
0.1 μg of dmLTBiological
0.1 μg intramuscular dose of double mutant (LT R192G/L211A) enterotoxigenic Escherichia coli heat labile toxin (dmLT).
PlaceboBiological
Placebo vaccination with commercially available saline solution.
| Study group | Role | What they receive |
|---|---|---|
| A1 - Low dose vaccine (Netherlands) | Experimental | 10 Dutch participants who receive three 2.5 μg doses of the vaccine without adjuvant at a 28-day interval in Cohort A. Receives: Biological: 2.5 μg InvaplexAR-Detox |
| A2 - Low dose vaccine + adjuvant (Netherlands) | Experimental | 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. Receives: Biological: 2.5 μg InvaplexAR-Detox; Biological: 0.1 μg of dmLT |
| B1/C1 - High dose vaccine (Netherlands & Zambia) | Experimental | 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. Receives: Biological: 10 μg InvaplexAR-Detox |
| B2/C2 - High dose vaccine + adjuvant (Netherlands & Zambia) | Experimental | 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. Receives: Biological: 10 μg InvaplexAR-Detox; Biological: 0.1 μg of dmLT |
| A3/B3/C3 - Placebo (Netherlands & Zambia) | Placebo comparator | 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. Receives: Biological: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Occurence of solicited adverse events
Occurrence of solicited adverse events considered to be (possibly, probably or definitely) related to vaccination according to the International Classification of Diseases version 11 (ICD-11) compared to the placebo group. Local solicited adverse events include pain/tenderness, erythema, induration/swelling, pruritus, and ipsilateral axillary lymphadenopathy. Systemic solicited adverse events include fever, chills, headache, fatigue, malaise, nausea/vomiting, painful/swollen joints, myalgia, diarrhea, and abdominal pain. Only symptoms with an onset after a vaccination until the 7th subsequent day after that vaccination will be considered solicited.
Measured: Within 7 days following vaccination (day of vaccination and 7 subsequent days).
Occurence of unsolicited adverse events
Occurrence of unsolicited adverse events considered to be (possibly, probably or definitely) related to vaccination, according to the ICD-11 classification.
Measured: Within 28 days following each vaccination (day of vaccination and 28 subsequent days).
Secondary outcomes (9)
Geometric mean titers of serum immunoglobulin A antibodies to Invaplex antigens
Serum GMTs of anti-LPS, anti-IpaB and anti-IpaC IgA
Measured: Study days 1 (baseline), 29, 57, 64, 85 and 225.
Geometric mean titers of serum immunoglobulin G antibodies to Invaplex antigens
Serum GMTs of anti-LPS, anti-IpaB and anti-IpaC IgG
Measured: Study days 1 (baseline), 29, 57, 64, 85 and 225.
Proportion of participants with immunoglobulin A seroconversion (> 4-fold rise in titer over baseline)
Percentage of participants wit a ≥ 4-fold increase in serum anti-LPS, anti-IpaB and anti-IpaC IgA titer from baseline
Measured: Study days 1 (baseline), 29, 57, 64, 85 and 225.
Proportion of participants with immunoglobulin G seroconversion (> 4-fold rise in titer over baseline)
Percentage of participants wit a ≥ 4-fold increase in serum anti-LPS, anti-IpaB and anti-IpaC IgG titer from baseline
Measured: Study days 1 (baseline), 29, 57, 64, 85 and 225.
Serum bactericidal assay response to S. flexneri 2a, strain 2457T in geometric mean titers
Measured: Study days 1 (baseline), 29, 57, 64, and 85.
Proportion of participants with serum bactericidal assay responses (≥ 4-fold rise over baseline) to S. flexneri 2a, strain 2457T
Measured: Study days 1 (baseline), 29, 57, 64, and 85.
Geometric mean titers of α4β7 antibodies in lymphocyte supernatant.
Measured: Study days 1 (baseline), 8, 36, and 64
B cell memory responses to Invaplex antigens
B cell memory responses to the LPS and IpaB and IpaC antigens.
Measured: Study days 1 (baseline), 64 and 225
T cell memory responses to Invaplex antigens
T cell memory responses to the LPS and IpaB and IpaC antigens.
Measured: Study days 1 (baseline), 64 and 225
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jul 2023
- Study start10 Oct 2024
- Primary completionMay 2025 (estimated)
- Study completionMay 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for ShigellosisStudies of the same condition, open and under way.
- More trials run by Leiden University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Factorial
- Model description
- A phase Ia/b dose escalation, randomized, double-blind, placebo-controlled clinical trial
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 85 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Leiden University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Centre for Infectious Disease Research in Zambia, PATH, Walter Reed Army Institute of Research (WRAIR), Göteborg University, European Vaccine Initiative, European and Developing Countries Clinical Trials Partnership (EDCTP)
- Responsible party
- Principal investigator, Meta Roestenberg, Leiden University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05961059
- Sponsor's protocol ID
- SUNSHINE
- Acronym
- SUNSHINE
- Status last verified
- Nov 2024
- First submitted
- 5 Jul 2023
- Last updated
- 7 Nov 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data of the trial will follow the FAIR (findable, accessible, interoperable and re-usable) principles for data collection and sharing outlined by force11 and metadata will be entered in a repository which will be open access after completion of the trial.
Publications
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.
PubMed 39852827
Study at a glance
From the registry record, last updated by the sponsor on 7 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase Ia/b Double-blind, Placebo-controlled, Dose Escalating Safety Study of Detoxified Shigella Flexneri 2a Artificial Invasin Complex (InvaplexAR-Detox) Vaccine Formulated with and Without DmLT Adjuvant Given Intramuscularly to Healthy Adults in the Netherlands and Zambia
- ClinicalTrials.gov ID
- NCT05961059
- Acronym / sponsor ID
- SUNSHINE / SUNSHINE
- Conditions
- Shigellosis, Bacillary Dysentery
- Keywords
- Vaccine, Invaplex, dmLT, Shigella
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 85 participants (estimated)
- Lead sponsor
- Leiden University Medical CenterUniversity, hospital or other
- Collaborators
- Centre for Infectious Disease Research in Zambia, PATH, Walter Reed Army Institute of Research (WRAIR), Göteborg University, European Vaccine Initiative, European and Developing Countries Clinical Trials Partnership (EDCTP)
- Study start
- 10 Oct 2024 (actual)
- Primary completion
- May 2025 (estimated)
- Study completion
- May 2025 (estimated)
- First posted
- 27 Jul 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 5
- Model description
- A phase Ia/b dose escalation, randomized, double-blind, placebo-controlled clinical trial
| Arm | Type | Receives |
|---|---|---|
| A1 - Low dose vaccine (Netherlands) | Experimental | Biological: 2.5 μg InvaplexAR-Detox10 Dutch participants who receive three 2.5 μg doses of the vaccine without adjuvant at a 28-day interval in Cohort A. |
| A2 - Low dose vaccine + adjuvant (Netherlands) | Experimental | Biological: 2.5 μg InvaplexAR-Detox, Biological: 0.1 μg of dmLT10 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. |
| B1/C1 - High dose vaccine (Netherlands & Zambia) | Experimental | Biological: 10 μg InvaplexAR-Detox10 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. |
| B2/C2 - High dose vaccine + adjuvant (Netherlands & Zambia) | Experimental | Biological: 10 μg InvaplexAR-Detox, Biological: 0.1 μg of dmLT10 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. |
| A3/B3/C3 - Placebo (Netherlands & Zambia) | Placebo comparator | Biological: Placebo5 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. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (27 listed)
- Healthy adult, male or female, aged 18 to 50 years (inclusive) at the time of inclusion (=vaccination).
- Provide written informed consent before initiation of any study procedures.
- Available to complete all study visits and procedures.
- Negative stool PCR test for Shigella.
- 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.
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 2.5 μg InvaplexAR-Detox2.5 μg intramuscular dose of Sfl2a InvaplexAR-Detox. | Biological | A1 - Low dose vaccine (Netherlands), A2 - Low dose vaccine + adjuvant (Netherlands) |
| 10 μg InvaplexAR-Detox10 μg intramuscular dose of Sfl2a InvaplexAR-Detox. | Biological | B1/C1 - High dose vaccine (Netherlands & Zambia), B2/C2 - High dose vaccine + adjuvant (Netherlands & Zambia) |
| 0.1 μg of dmLT0.1 μg intramuscular dose of double mutant (LT R192G/L211A) enterotoxigenic Escherichia coli heat labile toxin (dmLT). | Biological | A2 - Low dose vaccine + adjuvant (Netherlands), B2/C2 - High dose vaccine + adjuvant (Netherlands & Zambia) |
| PlaceboPlacebo vaccination with commercially available saline solution. | Biological | A3/B3/C3 - Placebo (Netherlands & Zambia) |
Primary outcome
Occurence of solicited adverse events
Time frame: Within 7 days following vaccination (day of vaccination and 7 subsequent days).
Occurrence of solicited adverse events considered to be (possibly, probably or definitely) related to vaccination according to the International Classification of Diseases version 11 (ICD-11) compared to the placebo group. Local solicited adverse events include pain/tenderness, erythema, induration/swelling, pruritus, and ipsilateral axillary lymphadenopathy. Systemic solicited adverse events include fever, chills, headache, fatigue, malaise, nausea/vomiting, painful/swollen joints, myalgia, diarrhea, and abdominal pain. Only symptoms with an onset after a vaccination until the 7th subsequent day after that vaccination will be considered solicited.
Occurence of unsolicited adverse events
Time frame: Within 28 days following each vaccination (day of vaccination and 28 subsequent days).
Occurrence of unsolicited adverse events considered to be (possibly, probably or definitely) related to vaccination, according to the ICD-11 classification.
9 secondary outcomes
Geometric mean titers of serum immunoglobulin A antibodies to Invaplex antigens
Time frame: Study days 1 (baseline), 29, 57, 64, 85 and 225.
Geometric mean titers of serum immunoglobulin G antibodies to Invaplex antigens
Time frame: Study days 1 (baseline), 29, 57, 64, 85 and 225.
Proportion of participants with immunoglobulin A seroconversion (> 4-fold rise in titer over baseline)
Time frame: Study days 1 (baseline), 29, 57, 64, 85 and 225.
Proportion of participants with immunoglobulin G seroconversion (> 4-fold rise in titer over baseline)
Time frame: Study days 1 (baseline), 29, 57, 64, 85 and 225.
Serum bactericidal assay response to S. flexneri 2a, strain 2457T in geometric mean titers
Time frame: Study days 1 (baseline), 29, 57, 64, and 85.
Proportion of participants with serum bactericidal assay responses (≥ 4-fold rise over baseline) to S. flexneri 2a, strain 2457T
Time frame: Study days 1 (baseline), 29, 57, 64, and 85.
Geometric mean titers of α4β7 antibodies in lymphocyte supernatant.
Time frame: Study days 1 (baseline), 8, 36, and 64
B cell memory responses to Invaplex antigens
Time frame: Study days 1 (baseline), 64 and 225
T cell memory responses to Invaplex antigens
Time frame: Study days 1 (baseline), 64 and 225
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Nov 2024.
- Derived from this study: PubMed 39852827Roozen 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.
- Individual participant dataSharing planned: Yes. Data of the trial will follow the FAIR (findable, accessible, interoperable and re-usable) principles for data collection and sharing outlined by force11 and metadata will be entered in a repository which will be open access after completion of the trial.
Related trials for Shigellosis
RecruitingPhase 2
Long-Term Immunogenicity of the altSonflex1-2-3 Shigella Vaccine in African Children
Diarrhoea
Not yet recruitingPhase 1/2
Safety and Immunogenicity Study of IP-QSV Vaccine in Healthy Adults/Adolescents, Children and Infants
Shigella Infection
Active, not recruitingPhase 3
Clinical Trial of the S. Flexneri-S. Sonnei Bivalent Conjugate Vaccine
Dysentery, Dysentery, Shigella
RecruitingPhase 2
The Impact of Shigellosis and Recommended Treatment in Children
Diarrhea Infectious, Shigella
RecruitingPhase 1
First in Human Dose Escalation Study Evaluating the Safety and Immunogenicity of IVT's Shigella-04 Vaccine in Healthy Young Adults
Shigella, Diarrhea
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Maxim Bax, MD contact
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing 2.5 μg InvaplexAR-Detox, 10 μg InvaplexAR-Detox and 0.1 μg of dmLT in people with Shigellosis and Bacillary Dysentery, run by Leiden University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 27 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 7 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Meta Roestenberg, MD, PhD (+3171715262613, M.Roestenberg@lumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Occurence of solicited adverse events (time frame: Within 7 days following vaccination (day of vaccination and 7 subsequent days).). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05961059, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Nov 2024.