A Phase 1 interventional study of 2.5 μg InvaplexAR-Detox and 10 μg InvaplexAR-Detox in Shigellosis and Bacillary Dysentery, sponsored by Leiden University Medical Center. Recruiting at 1 site in Netherlands. Open to participants aged 18 Years to 50 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2024-11-07.
Sponsored by Leiden University Medical Center · Phase 1, Interventional, and Prevention
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:
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).
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.
61 studies on the registry are indexed under Dysentery, Bacillary; 6 are open to participants now.
This study's planned enrollment of 85 is above the median of 76 across 54 interventional studies indexed under Dysentery, Bacillary.
Browse Dysentery, Bacillary studies →Leiden University Medical Center is the lead sponsor of 334 studies on the registry; 110 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Inclusion Criteria:
Adequate methods of contraception for this study include:
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).
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Postmenopausal
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
10 Dutch participants who receive three 2.5 μg doses of the vaccine without adjuvant at a 28-day interval in Cohort A.
Biological: 2.5 μg InvaplexAR-Detox
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.
Biological: 2.5 μg InvaplexAR-Detox · Biological: 0.1 μg of dmLT
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.
Biological: 10 μg InvaplexAR-Detox
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.
Biological: 10 μg InvaplexAR-Detox · Biological: 0.1 μg of dmLT
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.
Biological: Placebo
2.5 μg intramuscular dose of Sfl2a InvaplexAR-Detox.
10 μg intramuscular dose of Sfl2a InvaplexAR-Detox.
0.1 μg intramuscular dose of double mutant (LT R192G/L211A) enterotoxigenic Escherichia coli heat labile toxin (dmLT).
Placebo vaccination with commercially available saline solution.
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.
Time frame: 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.
Time frame: Within 28 days following each vaccination (day of vaccination and 28 subsequent days).
Geometric mean titers of serum immunoglobulin A antibodies to Invaplex antigens
Serum GMTs of anti-LPS, anti-IpaB and anti-IpaC IgA
Time frame: 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
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)
Percentage of participants wit a ≥ 4-fold increase in serum anti-LPS, anti-IpaB and anti-IpaC IgA titer from 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)
Percentage of participants wit a ≥ 4-fold increase in serum anti-LPS, anti-IpaB and anti-IpaC IgG titer from 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
B cell memory responses to the LPS and IpaB and IpaC antigens.
Time frame: 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.
Time frame: Study days 1 (baseline), 64 and 225
Plan to share: 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.
Time frame: After completion of the trial. Specific timepoint to be decided.
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