Back to resultsA Phase 2 Bridging Study to Assess the New Formulation of ETVAX
Primary Purpose
Healty Volunteers, Preventable Disease, Vaccine
Status
Completed
Phase
Phase 2
Locations
Sweden
Study Type
Interventional
Intervention
Etvax
Etvax
Sponsored by
About this trial
This is an interventional prevention trial for Healty Volunteers focused on measuring Prophylaxis against diarrhea due to enterotoxigenic E. coli
Eligibility Criteria
Inclusion Criteria:
- Male or female aged 18-50 years, inclusive at the time of signing the informed consent.
- Healthy constitution as established by medical history and physical examination.
- Willing and able to give written informed consent for participation in the study.
- Able to comply with study activities, as judged by the Investigator.
- Female Participants:
- Women of child-bearing potential (for definition see Section 9.3.6 in the protocol):
- Have to agree to use an acceptable birth control method during participation in the investigation (see Section 9.3.6).
- A negative pregnancy test (beta human chorionic gonadotropin dipstick test in urine) at Visit 2/Day 1 will be required.
- Male Participants:
- Have to agree to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm, as defined in Section 9.3.6
Exclusion criteria
- An acute or chronic medical condition that, in the opinion of the investigator/physician, would render ingestion of the investigational products unsafe or would interfere with the evaluation of responses. This includes, but is not limited to gastrointestinal diseases, and autoimmune diseases.
- Current malignancy or history of malignancy during the last five years, based on anamnesis.
- Gastroenteritis within two weeks prior to vaccination.
- Regular use of laxatives, antacids or other agents that lower stomach acidity.
- Any planned major surgery during the duration of the study.
- After 10 minutes supine rest, any vital signs outside the following ranges:
- Systolic BP > 160 mm Hg
- Diastolic BP > 100 mm Hg
- Heart rate < 40 or >85 beats per minute
- Antibiotic therapy within two weeks prior to the vaccination.
- Known Hepatitis A, B, C, and/or HIV infection.
- Concomitant intake of immunomodulating drugs during the study period or less than 3 months prior to the first immunization. Local anti-histamine treatment is however allowed.
- Any other significant medical conditions (e.g. poorly controlled psychiatric condition) judged by the Investigator to preclude entry.
- Intends to receive any other vaccine during the study period, or within two weeks prior to trial vaccination.
- Has previously received Dukoral or any type of ETEC or cholera vaccines.
- Brought up in ETEC-endemic areas (e.g., urban and rural areas of Central and South America, Caribbean, most countries in Asia, Africa, etc.).
- Has travelled to ETEC-endemic areas within the last 3 years OR spent > two months in ETEC endemic areas during the last 10 years.
- Intends to travel to ETEC endemic countries during the study period.
- Known or suspected history of drug, chemical or alcohol abuse, as deemed by the investigator/physician.
- History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the Investigator, or history of hypersensitivity to drugs with a similar chemical structure or class to ETVAX®.
- Participation in any other clinical study that included drug treatment with the last administration within the past 3 months prior to administration of study treatment in this study. Patients consented and screened but not dosed in previous clinical studies are not excluded.
- Concomitant participation in any other clinical study.
- Females who are pregnant as determined by urine test at inclusion and prior to each vaccination.
- Females who are nursing.
- Unable to participate in all study visits.
- Any condition or circumstance which would make the subject unsuitable for participation in the study in the opinion of the investigator/physician.
Sites / Locations
- Clinical Trial Center, CTC
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
The wet formulation of ETVAX.
The partially dried formulation of selected components of ETVAX.
Arm Description
The wet formulation consists of a liquid suspension of inactivated bacteria (ETEX 21-24) and LCTBA in one vial, freeze-dried dmLT adjuvant in a second vial, and effervescent buffer granules in a separate sachet. Prior to administration, the buffer is dissolved in 150 ml tap water, followed by the addition of the content of the vaccine vial (inactivated bacteria mixed with LCTBA) and reconstituted and diluted adjuvant dmLT from the second vial.
The partially dried formulation, dmLT and LCTBA are spray-dried and mixed with the buffer granules and stabilizing excipients in a sachet. Prior to administration, the content of the buffer sachet (buffer, dmLT, and LCTBA) is dissolved in 150 ml tap water, followed by the addition of a liquid suspension of inactivated bacteria (ETEX 21-24).
Outcomes
Primary Outcome Measures
Vaccine response
The primary endpoint to be measured for each patient in the study is response (yes/no) to a vaccine. A vaccine responder will be defined by a ≥2-fold increase in IgA and/or IgG antibody levels against LTB in serum between post- compared to pre-immunization samples. The response rates (seroconversion rates) of IgA and/or IgG anti-LTB antibodies in serum will be derived and compared between the two treatment groups.
Secondary Outcome Measures
Solicited symptoms after vaccination
Occurrence of solicited symptoms for six days after each vaccination (day of vaccination and five subsequent days).
Full Information
NCT ID
NCT05178134
First Posted
December 3, 2021
Last Updated
January 11, 2023
Sponsor
Scandinavian Biopharma AB
Collaborators
Göteborg University, Scandinavian CRO, Sahlgrenska University Hospital, Sweden
1. Study Identification
Unique Protocol Identification Number
NCT05178134
Brief Title
A Phase 2 Bridging Study to Assess the New Formulation of ETVAX
Official Title
A Phase 2 Immunological Bridging Study Assessing the Non-inferiority of a New Formulation of ETVAX®. A Prospective Double-blind, Randomized Study in Healthy Volunteers.
Study Type
Interventional
2. Study Status
Record Verification Date
January 2023
Overall Recruitment Status
Completed
Study Start Date
November 8, 2021 (Actual)
Primary Completion Date
October 20, 2022 (Actual)
Study Completion Date
October 20, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Scandinavian Biopharma AB
Collaborators
Göteborg University, Scandinavian CRO, Sahlgrenska University Hospital, Sweden
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
This is a phase 2,prospective double-blind, randomized, parallel-group study with the aim to demonstrate non-inferiority, in terms of immunogenicity, between the wet formulation and a newly developed partially dried formulation of selected components of ETVAX.
Detailed Description
This is a phase 2, prospective double-blind, randomized, parallel-group study with the aim to demonstrate non-inferiority, in terms of immunogenicity, between the wet formulation and a newly developed partially dried formulation of selected components of ETVAX.. A total number of 126 subjects will be included in each arm of the study, i.e. 252 subjects in total. Assuming a 10% dropout rate the target number of subjects to be recruited per study arm is therefore 140, i.e. 280 subjects in total. Healthy volunteers between 18-50 years will be eligible for enrolment into the study.
Eligible subjects will be randomized on Day 1 (Visit 2) to receive either of the two oral formulations of ETVAX (1:1) and consecutively included the study. The treatment allocation (Wet formulation/Partially dried formulation) will be double-blind. The study subjects will receive two oral doses, two weeks apart (Day 1/Visit 2 and Day 15 /Visit 3).The dosing will occur at the clinic (CTC in Gothenburg, Sweden). A follow-up visit will be performed 7 days after the last (second) dose in all study subjects
The primary endpoint to be measured for each patient in the study is response (yes/no) to a vaccine. A vaccine responder will be defined by a ≥2-fold increase in IgA and/or IgG antibody levels against LTB in serum between post- compared to pre-immunization samples. The response rates (seroconversion rates) of IgA and/or IgG anti-LTB antibodies in serum will be derived and compared between the two treatment groups.
The secondary endpoint to be measured for each patient in the study is the occurrence of solicited symptoms for six days after each vaccination (day of vaccination and five subsequent days).
Exploratory analyses will be done to evaluate if ETVAX vaccination induces circulating antigen specific memory B- and/or T cells that can be assessed using recently established laboratory assays.
For the exploratory analyses, subgroups of subjects (n=20-40, evenly distributed between the two treatment arms) will participate in additional follow-up visits 5± 1, 30± 7 and 90± 14 days after the second dose. Blood samples will be collected on all exploratory visits. The extra visits and analyses for exploratory analyses may continue after the main part of the study has been completed and the database locked.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Healty Volunteers, Preventable Disease, Vaccine
Keywords
Prophylaxis against diarrhea due to enterotoxigenic E. coli
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
A randomized, placebo controlled phase 2
Masking
ParticipantCare ProviderInvestigator
Masking Description
Other parts will be blinded except unblinded person who prepares the doses
Allocation
Randomized
Enrollment
280 (Actual)
8. Arms, Groups, and Interventions
Arm Title
The wet formulation of ETVAX.
Arm Type
Active Comparator
Arm Description
The wet formulation consists of a liquid suspension of inactivated bacteria (ETEX 21-24) and LCTBA in one vial, freeze-dried dmLT adjuvant in a second vial, and effervescent buffer granules in a separate sachet. Prior to administration, the buffer is dissolved in 150 ml tap water, followed by the addition of the content of the vaccine vial (inactivated bacteria mixed with LCTBA) and reconstituted and diluted adjuvant dmLT from the second vial.
Arm Title
The partially dried formulation of selected components of ETVAX.
Arm Type
Active Comparator
Arm Description
The partially dried formulation, dmLT and LCTBA are spray-dried and mixed with the buffer granules and stabilizing excipients in a sachet. Prior to administration, the content of the buffer sachet (buffer, dmLT, and LCTBA) is dissolved in 150 ml tap water, followed by the addition of a liquid suspension of inactivated bacteria (ETEX 21-24).
Intervention Type
Biological
Intervention Name(s)
Etvax
Intervention Description
Preparation of complete Wet formulation. The vaccine supplied as a liquid, is mixed with the 150 ml of sodium bicarbonate buffer solution on the day of preparation for use on dosing day.
Just prior to administration 10 µg of dmLT is added by pipette (50 µl).
Intervention Type
Biological
Intervention Name(s)
Etvax
Intervention Description
Preparation of partially dry formulation. The partially dry formulation of vaccine is prepared by adding the effervescent powder containing the dmLT and LCTBA to 150 ml of water. After mixing, the content of the vaccine vial is added to the mixture and the vaccine is administered to the volunteer within 30 minutes after adding the buffer powder to the water.
Primary Outcome Measure Information:
Title
Vaccine response
Description
The primary endpoint to be measured for each patient in the study is response (yes/no) to a vaccine. A vaccine responder will be defined by a ≥2-fold increase in IgA and/or IgG antibody levels against LTB in serum between post- compared to pre-immunization samples. The response rates (seroconversion rates) of IgA and/or IgG anti-LTB antibodies in serum will be derived and compared between the two treatment groups.
Time Frame
3 weeks
Secondary Outcome Measure Information:
Title
Solicited symptoms after vaccination
Description
Occurrence of solicited symptoms for six days after each vaccination (day of vaccination and five subsequent days).
Time Frame
3 weeks
Other Pre-specified Outcome Measures:
Title
Levels of IgA and IgG antibodies mononuclear cells (PBMCs)
Description
Evaluation if ETVAX® vaccination induces circulating antigen specific memory B- and/or T cells.
Time Frame
3 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Male or female aged 18-50 years, inclusive at the time of signing the informed consent.
Healthy constitution as established by medical history and physical examination.
Willing and able to give written informed consent for participation in the study.
Able to comply with study activities, as judged by the Investigator.
Female Participants:
Women of child-bearing potential (for definition see Section 9.3.6 in the protocol):
Have to agree to use an acceptable birth control method during participation in the investigation (see Section 9.3.6).
A negative pregnancy test (beta human chorionic gonadotropin dipstick test in urine) at Visit 2/Day 1 will be required.
Male Participants:
Have to agree to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm, as defined in Section 9.3.6
Exclusion criteria
An acute or chronic medical condition that, in the opinion of the investigator/physician, would render ingestion of the investigational products unsafe or would interfere with the evaluation of responses. This includes, but is not limited to gastrointestinal diseases, and autoimmune diseases.
Current malignancy or history of malignancy during the last five years, based on anamnesis.
Gastroenteritis within two weeks prior to vaccination.
Regular use of laxatives, antacids or other agents that lower stomach acidity.
Any planned major surgery during the duration of the study.
After 10 minutes supine rest, any vital signs outside the following ranges:
Systolic BP > 160 mm Hg
Diastolic BP > 100 mm Hg
Heart rate < 40 or >85 beats per minute
Antibiotic therapy within two weeks prior to the vaccination.
Known Hepatitis A, B, C, and/or HIV infection.
Concomitant intake of immunomodulating drugs during the study period or less than 3 months prior to the first immunization. Local anti-histamine treatment is however allowed.
Any other significant medical conditions (e.g. poorly controlled psychiatric condition) judged by the Investigator to preclude entry.
Intends to receive any other vaccine during the study period, or within two weeks prior to trial vaccination.
Has previously received Dukoral or any type of ETEC or cholera vaccines.
Brought up in ETEC-endemic areas (e.g., urban and rural areas of Central and South America, Caribbean, most countries in Asia, Africa, etc.).
Has travelled to ETEC-endemic areas within the last 3 years OR spent > two months in ETEC endemic areas during the last 10 years.
Intends to travel to ETEC endemic countries during the study period.
Known or suspected history of drug, chemical or alcohol abuse, as deemed by the investigator/physician.
History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the Investigator, or history of hypersensitivity to drugs with a similar chemical structure or class to ETVAX®.
Participation in any other clinical study that included drug treatment with the last administration within the past 3 months prior to administration of study treatment in this study. Patients consented and screened but not dosed in previous clinical studies are not excluded.
Concomitant participation in any other clinical study.
Females who are pregnant as determined by urine test at inclusion and prior to each vaccination.
Females who are nursing.
Unable to participate in all study visits.
Any condition or circumstance which would make the subject unsuitable for participation in the study in the opinion of the investigator/physician.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dan Curiac, MD
Organizational Affiliation
Clinical Trial Center, CTC, Gothia Forum
Official's Role
Principal Investigator
Facility Information:
Facility Name
Clinical Trial Center, CTC
City
Göteborg
ZIP/Postal Code
41346
Country
Sweden
12. IPD Sharing Statement
Learn more about this trial
A Phase 2 Bridging Study to Assess the New Formulation of ETVAX
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