A Double-Blind Placebo-Control Dose Escalating Study to Evaluate the Safety and Immunogenicity of dmLT by Oral, Sublingual and Intradermal Vaccination in Adults Residing in an Endemic Area

• Register: ClinicalTrials.gov
• Last refreshed on: 26 July 2021
• Main ID: NCT03548064
• Date of registration: 24/05/2018
• Prospective Registration: Yes
• Primary sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Public title: A Double-Blind Placebo-Control Dose Escalating Study to Evaluate the Safety and Immunogenicity of dmLT by Oral, Sublingual and Intradermal Vaccination in Adults Residing in an Endemic Area
• Scientific title: A Phase 1 Double-Blinded, Placebo-Controlled, Dose Escalation Study to Evaluate the Safety and Immunogenicity of Double Mutant Heat-Labile Toxin LTR192G/L211A (dmLT) From Enterotoxigenic Escherichia Coli (ETEC) by Oral, Sublingual, or Intradermal Vaccination in Adults Residing in an Endemic Area
• Date of first enrolment: March 10, 2019
• Target sample size: 75
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT03548064
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Sequential Assignment. Primary purpose: Prevention. Masking: Double (Participant, Investigator).
• Phase: Phase 1

Countries of recruitment

Bangladesh

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Male or female age 18-45 years old, inclusive.

2. Provides written informed consent before initiation of any study procedures.

3. Healthy as judged by the site investigators and determined by medical history,
medication history, and physical examination.

4. Capable of understanding, consenting, and complying with all the study visits and
procedures.

5. Body Mass Index of no less than 18.5.

6. Agrees not to participate in another clinical trial during the study period.

7. Agrees to complete all study visits and procedures.

8. Agrees not to donate blood to a blood bank for 12 months after receiving the last
vaccine.

Exclusion Criteria:

1. Women who are pregnant or lactating or have a positive urine pregnancy test at
screening or on the day of vaccinations.

Note: all women presenting for screening will have urine pregnancy testing. "Females
of childbearing potential must agree to use an efficacious hormonal or barrier method
of birth control from screening and through 28 days post last dose of vaccine.
Abstinence is also acceptable."

2. Presence or history of a chronic medical condition* that would, in the opinion of the
investigator, render vaccination unsafe or interfere with the evaluation of the
vaccine.

*Note: this may include, but is not limited to: significant renal disease, unstable or
progressive neurological disorders, diabetes, heart disease, asthma, lung disease,
liver disease, organ transplant recipients and cancer.

3. Presence of a significant dermatologic condition*, or tattoo(s), scarring or
significant skin damage at the vaccination site that would impede evaluation of local
reactogenicity.

*Note: this may include severe eczema, psoriasis or history of keloid formation.
Participants with history of squamous cell or basal cell skin cancer that has been
surgically excised and considered cured may be enrolled in the study if the skin
cancer site is healed and is not at proposed vaccine administration site.

4. Any developmental abnormality of the palate.

5. Participants diagnosed with autoimmune disorders, chronic inflammatory disorders or
neurological disorders with a potential autoimmune correlation.

6. Use of long-term (> / = 2 weeks) oral steroids, intranasal or topical prednisone (or
equivalent), parenteral steroids, or high-dose inhaled steroids (> 800 microgram/day
of beclomethasone dipropionate or equivalent) within the preceding 6 months.

7. Has major psychiatric illness* during last 12 months that in the investigator's
opinion would preclude participation.

*Note: Participants taking antipsychotic or antimanic drugs should not be enrolled.
These include: aripiprazole, clozapine, ziprasidone, haloperidol, molindone,
lamotrigine, gabapentin, topiramate, loxapine, thioridazine, thiothixene, pimozide,
fluphenazine, risperidone, mesoridazine, quetiapine, trifluoperazine, chlorprothixene,
chlorpromazine, perphenazine, olanzapine, carbamazepine, divalproex sodium, lithium
carbonate, or lithium citrate. Participants taking a single antidepressant drug and
are stable without de-compensating symptoms in the preceding 3 months can be enrolled
in the study.

8. Use of prescription or over-the-counter (OTC) anti-inflammatory medications* 48 hours
prior to receiving the investigational product.

*Note: This includes naproxen, aspirin, ibuprofen, and other non-steroidal
anti-inflammatory drugs.

9. Gastrointestinal symptoms* in the past 24 hours or abdominal pain lasting for more
than 2 weeks in the past 6 months.

*Note: this may include, but is not limited to: abdominal pain or cramps, loss of
appetite, nausea, general ill-feeling or vomiting.

10. Moderate or severe diarrheal illness* during the 6 weeks prior to enrollment.

*Note: Moderate or severe diarrheal illness is defined by the passage of > / = 4
unformed or loose stools (mix of liquid and solid components) in a 24 hour period

11. History of chronic gastrointestinal illness*.

*Note: this includes severe dyspepsia or gastroesophageal reflux disease,
constipation, irritable bowel syndrome (IBS), hemorrhoids, diverticular disease,
colitis, colon polyps, colon cancer, and inflammatory bowel disease. Mild or moderate
heartburn or epigastric pain occurring no more than three times per week is permitted.

12. Regular use (weekly or more often) of laxatives, anti-diarrheal, anti-constipation, or
antacid therapy.

13. History of major gastrointestinal surgery, excluding uncomplicated appendectomy or
cholecystectomy.

14. History of systemic antimicrobial treatment (i.e., topical treatments are not an
exclusion) during the week prior to any administration of dmLT.

15. Acute febrile illness (body temperature > / = 38 degrees Celsius) during the week
prior to enrollment.

16. Abnormal screening laboratories. Note: screening labs include white blood cell count
(WBC), absolute neutrophil count (ANC), hemoglobin (Hg), platelet count, serum
creatinine, serum albumin, alanine aminotransferase (ALT, also known as SGPT), and
serologic testing for Hepatitis B virus surface antigen (HBsAg) and Hepatitis C virus
(HCV) antibody. Abnormal vital signs.

17. Isolation of specific bacteria* from screening stool cultures.

*Note: bacteria include ETEC, Vibrio cholerae, and Shigella spp. Salmonella and
Campylobacter will not be evaluated as part this criterion.

18. Received an inactivated licensed vaccine within 2 weeks of enrollment or live licensed
vaccine within 4 weeks of enrollment.

19. Received a cholera (licensed or experimental) vaccine, E. coli vaccine, or Shigella
vaccine in the last 3 years.

20. History of receiving immune globulin or other blood product within the 3 months before
enrollment in this study.

21. Currently enrolled in another study, involving an experimental agent. Participants
involved in observational studies or surveys remain eligible.

22. Any condition that would, in the opinion of the Site Investigator, place the
participant at an unacceptable risk of injury or render the participant unable to meet
the requirements of the protocol.

23. Known allergies to study compound or components of the study vaccine.

24. Donating blood in the 8 weeks prior to study entry.



Age minimum: 18 Years
Age maximum: 45 Years
Gender: All

Health Condition(s) or Problem(s) studied

Immunisation

Gastroenteritis Escherichia Coli

Intervention(s)

Biological: Recombinant Double Mutant Heat-Labile Toxin LT(R192G/L211A) (dmLT) Oral enterotoxigenic Escherichia coli (ETEC) Vaccine

Other: Placebo

Primary Outcome(s)

The occurrence of study withdrawals [Time Frame: Day 1 up to day 223]

The occurrence of systemic reactogenicity events [Time Frame: Day 1 to day 8]

The occurrence of systemic reactogenicity events [Time Frame: Day 15 to day 36]

The occurrence of systemic reactogenicity events [Time Frame: Day 43 to day 50]

The occurrence of discontinuation of study vaccination [Time Frame: Day 1 up to day 223]

The occurrence of solicited local site events [Time Frame: Day 43 to day 50]

The occurrence of solicited local site events [Time Frame: Day 15 to day 36]

The occurrence of unsolicited vaccine-related adverse events (AE), including laboratory AE [Time Frame: Day 1 to day 71]

The occurrence of solicited local site events [Time Frame: Day 1 to day 8]

Secondary Outcome(s)

The occurrence of vaccine-related serious adverse events (SAE) [Time Frame: Day 1 up to day 223]

The proportion of participants with = / > 2-fold rise in ALS anti-dmLT-specific IgA titers over baseline measured by ELISA [Time Frame: Day 1 to day 114]

The proportion of participants with a = / > 4-fold rise in dmLT-specific serum IgA titers over baseline measured by ELISA [Time Frame: Day 1 to day 114]

The proportion of participants with a = / > 4-fold rise in dmLT-specific serum IgG titers over baseline measured by ELISA [Time Frame: Day 1 to day 114]

The proportion of participants with >8 dmLT-specific IgA or IgG ASC / 10^6 PBMC as measured by ELISpot [Time Frame: Day 1 to day 114]

The proportion of participants with = / > 2-fold rise in ALS anti-dmLT-specific IgG titers over baseline measured by ELISA [Time Frame: Day 1 to day 114]

The proportion of participants with a = / > 4-fold rise over baseline in dmLT-specific fecal IgA titers measured by ELISA [Time Frame: Day 1 to day 57]

The proportion of participants with a = / > 4-fold rise over baseline in dmLT-specific salivary IgA titers measured by ELISA [Time Frame: Day 1 to day 57]

Secondary ID(s)

HHSN272201300022I

14-0031

Source(s) of Monetary Support

Please refer to primary and secondary sponsors