InvaplexAR-Detox and DmLT Adjuvant in the Netherlands and Zambia

NCT05961059 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: SUNSHINE
• Study Type: interventional
• Target: 85
• Locations: 1 country
• Sites: 1

Brief 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 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).

Conditions

Shigellosis; Bacillary Dysentery

Keywords

Vaccine; Invaplex; dmLT; Shigella

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  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

  Study days 1 (baseline), 29, 57, 64, 85 and 225.

• Geometric mean titers of serum immunoglobulin G antibodies to Invaplex antigens

  Study days 1 (baseline), 29, 57, 64, 85 and 225.

• Proportion of participants with immunoglobulin A seroconversion (> 4-fold rise in titer over baseline)

  Study days 1 (baseline), 29, 57, 64, 85 and 225.

• Proportion of participants with immunoglobulin G seroconversion (> 4-fold rise in titer over baseline)

  Study days 1 (baseline), 29, 57, 64, 85 and 225.

• Serum bactericidal assay response to S. flexneri 2a, strain 2457T in geometric mean titers

  Study days 1 (baseline), 29, 57, 64, and 85.

Study Arms (5)

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.

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.

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.

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.

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.

Biological: Placebo

Interventions

2.5 μg InvaplexAR-Detox BIOLOGICAL

2.5 μg intramuscular dose of Sfl2a InvaplexAR-Detox.

A1 - Low dose vaccine (Netherlands); A2 - Low dose vaccine + adjuvant (Netherlands)

10 μg InvaplexAR-Detox BIOLOGICAL

10 μg intramuscular dose of Sfl2a InvaplexAR-Detox.

B1/C1 - High dose vaccine (Netherlands & Zambia); B2/C2 - High dose vaccine + adjuvant (Netherlands & Zambia)

0.1 μg of dmLT BIOLOGICAL

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

A2 - Low dose vaccine + adjuvant (Netherlands); B2/C2 - High dose vaccine + adjuvant (Netherlands & Zambia)

Placebo BIOLOGICAL

Placebo vaccination with commercially available saline solution.

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

Eligibility Criteria

• Age: 18 Years - 50 Years
• Gender Eligibility Details: Self-identified male or female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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:
• \. 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).
• \. 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.

Sponsors & Collaborators

• Leiden University Medical Center: lead
• Centre for Infectious Disease Research in Zambia: collaborator
• PATH: collaborator
• Walter Reed Army Institute of Research (WRAIR): collaborator
• Göteborg University: collaborator
• European Vaccine Initiative: collaborator
• European and Developing Countries Clinical Trials Partnership (EDCTP): collaborator

Study Sites (1)

Leiden University Medical Center

Leiden, 2333 ZA, Netherlands

RECRUITING

Related Publications (1)

• 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.

  PMID: 39852827 DERIVED

MeSH Terms

Conditions

Dysentery, Bacillary

Condition Hierarchy (Ancestors)

Enterobacteriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Dysentery; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Central Study Contacts

Meta Roestenberg, MD, PhD

CONTACT

+3171715262613; M.Roestenberg@lumc.nl

Maxim Bax, MD

CONTACT

a.m.bax@lumc.nl

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Double blind
• Purpose: PREVENTION
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Priniciple Investigator

Model Details: A phase Ia/b dose escalation, randomized, double-blind, placebo-controlled clinical trial

Study Record Dates

• First Submitted: July 5, 2023
• First Posted: July 27, 2023
• Study Start: October 10, 2024
• Primary Completion: May 1, 2025
• Study Completion: May 1, 2025
• Last Updated: November 7, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share
• Time Frame: After completion of the trial. Specific timepoint to be decided.

Locations

NL (1)