A Study to Investigate the Safety and Immunogenicity of the SF2a-TT15 Synthetic Carbohydrate-based Conjugate Vaccine Against Shigella Flexneri 2a (GlycoShig3)

Pasteur Institute

Status and phase: Completed; Phase 2

Conditions: Healthy

Treatments: Biological: Injection SF2A-TT15 2 µg; Biological: Injection Adjuvanted Placebo; Biological: Injection SF2A-TT15 2 µg Adjuvanted; Biological: Injection SF2A-TT15 10 µg; Biological: Injection Placebo; Biological: Injection SF2A-TT15 10 µg Adjuvanted

Study type: Interventional

Funder types: Other; Industry; Other U.S. Federal agency

Identifiers

NCT04602975

2018-017

Details and patient eligibility

About

A study among adults, children and infants in Kenya to determine if a new type of glycoconjugate vaccine incorporating a synthetic carbohydrate component is safe and induces immunity against Shigella.

Full description

The purpose of this study is to examine the safety and immunogenicity of two doses of the parenteral synthetic carbohydrate-based conjugate vaccine against Shigella flexneri 2a (Shigella flexneri 2a-Tetanus Toxoid15 (SF2a-TT15)) adjuvanted or not with Alhydrogel in infants in an endemic country (Kenya), the target population for the vaccine, using an age-descending approach. In total, 232 participants will be enrolled in the study: 16 adults (18-50 years-old), 16 children (2-5 years-old) and 200 infants (9 months-old +/ 1 mo).

The vaccine will be tested in adults first, then in children and eventually in infants in Kenya (where Shigella infection is present), based on the safety/tolerability in each group before to moving to the other. Participants will be randomly assigned to receive the study vaccine or a placebo control (same solution but without the vaccine component). The participants will have to go through all the trial procedures including the 14 visits (3 injections and 11 follow-up) during a 16 months period.

Enrollment: 248 patients

Sex: All

Ages: 8 months to 50 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

For adults:

1. Healthy men and women between 18 and 50 (inclusive) years of age.
2. Subjects who provide written informed consent or thumb print in the presence of a witness to participate in the study
3. Women willing to use at least 1 reliable method of contraception during the study period, or are surgically sterilized, and agree to undergo repeated pregnancy tests (before each vaccination) and men willing to use an effective method of contraception (e.g. condom).

For children and infants:

1. Healthy boys and girls between 2 and 5 years of age for the children group (cohort 2)
2. Healthy boys and girls 9 mo-old (+/- 1 month) for the infant group (cohort 3)
3. Parents or legally acceptable representatives, as appropriate, who are willing and able to provide signed/thumb printed informed consent for children and infants.
4. Infant and children should have a normal nutritional Z score (-2 or greater) according to the mother and child health handbook of the republic of Kenya - Ministry of Health before entering the trial.

For all:

1. Signed/thumb written informed consent, in accordance with local practice, provided by adult volunteers (participants 18 years of age and older), parent(s) or legal representative(s) for children and infants participants as applicable, who, in the opinion of the Investigator, can and will comply with the requirements of the protocol.
2. Subjects in general good health in the opinion of the Investigator as determined by medical history, vital signs and a physical examination.
3. No clinically significant abnormalities in hematology, blood chemistry, or urinalysis laboratory tests at screening.
4. Negative HIV, Hepatitis B and Hepatitis C serology tests and malaria test.

Exclusion criteria

1. Subjects with a history of clinically significant gastrointestinal disorders (e.g. gastroesophageal reflux disease, peptic ulcer, celiac disease, inflammatory bowel disease).
2. Individuals with immunosuppressive diseases or under immunosuppressive therapy.
3. Previous participation in any study in which a Shigella-vaccine candidate was administered.
4. Suspected or known hypersensitivity (including allergy) to any of the vaccine components or to previous vaccine, or to medicinal products or medical equipment whose use is foreseen in this study.
5. Use of any prescription or over-the-counter (OTC) medications, within 14 days prior vaccination. Paracetamol or ibuprofen for symptomatic relief of pain is allowed until 48 hours prior to vaccination.
6. Women who are pregnant, breast-feeding, or are of childbearing age and are not on or do not plan to use acceptable contraceptives for the duration of the study.
7. Subjects with any significant acute medical situation (e.g. acute infection) within 48 hrs prior to study entry, in the opinion of the Principal Investigator.
8. Participation in another clinical trial with drugs within 3 months prior first study injection.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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248 participants in 12 patient groups, including a placebo group

Adults cohort 1 vaccinees

Experimental group

Description:

Eligible subjects (adults - 18 to 50 yr-old) will be randomized to receive 3 intramuscular (IM) injections with the 10μg OS adjuvanted dose (or matching placebo), at a ratio of 3:1.

Treatment:

Biological: Injection SF2A-TT15 10 µg Adjuvanted

Adults cohort 1 placebo recipients

Placebo Comparator group

Description:

Eligible subjects (adults - 18 to 50 yr-old) will be randomized to receive 3 IM injections with the adjuvanted matching placebo.

Treatment:

Biological: Injection Adjuvanted Placebo

Children cohort 2 vaccinees

Experimental group

Description:

Eligible subjects (Children 2 to 5 yr-old) will be randomized to receive 3 IM injections of the 10 μg OS dose with Alhydrogel (or matching placebo) at a ratio of 3:1.

Treatment:

Biological: Injection SF2A-TT15 10 µg Adjuvanted

Children cohort 2 placebo recipients

Placebo Comparator group

Description:

Eligible subjects (Children 2 to 5 yr-old) will be randomized to receive 3 IM injections of the matching placebo with Alhydrogel.

Treatment:

Biological: Injection Adjuvanted Placebo

Infants cohort 3A vaccinees (-)

Experimental group

Description:

Eligible subjects (9 mo-old +/- 1mo infants) will be randomized to receive 3 IM injections of the not adjuvanted 2 μg dose (or of matching placebo), at a ratio of 4:1.

Treatment:

Biological: Injection SF2A-TT15 2 µg

Infants cohort 3A placebo recipients (-)

Placebo Comparator group

Description:

Eligible subjects (9 mo-old +/- 1mo infants) will be randomized to receive 3 IM injections of the not adjuvanted matching placebo.

Treatment:

Biological: Injection Placebo

Infants cohort 3A vaccinees (+)

Experimental group

Description:

Eligible subjects (9 mo-old +/- 1mo infants) will be randomized to receive 3 IM injections of the adjuvanted 2 μg dose (or of matching placebo), at a ratio of 4:1.

Treatment:

Biological: Injection SF2A-TT15 2 µg Adjuvanted

Infants cohort 3A placebo recipients (+)

Placebo Comparator group

Description:

Eligible subjects (9 mo-old +/- 1mo infants) will be randomized to receive 3 IM injections of the adjuvanted matching placebo.

Treatment:

Biological: Injection Adjuvanted Placebo

Infants cohort 3B vaccinees (-)

Experimental group

Description:

Eligible subjects (9 mo-old +/- 1mo infants) will be randomized to receive 3 IM injections of the not adjuvanted 10 μg dose (or of matching placebo), at a ratio of 4:1.

Treatment:

Biological: Injection SF2A-TT15 10 µg

Infants cohort 3B placebo recipients (-)

Placebo Comparator group

Description:

Eligible subjects (9 mo-old +/- 1mo infants) will be randomized to receive 3 IM injections of the not adjuvanted matching placebo.

Treatment:

Biological: Injection Placebo

Infants cohort 3B vaccinees (+)

Experimental group

Description:

Eligible subjects (9 mo-old +/- 1mo infants) will be randomized to receive 3 IM injections of the adjuvanted 10 μg dose (or of matching placebo), at a ratio of 4:1.

Treatment:

Biological: Injection SF2A-TT15 10 µg Adjuvanted

Infants cohort 3B placebo recipients (+)

Placebo Comparator group

Description:

Eligible subjects (9 mo-old +/- 1mo infants) will be randomized to receive 3 IM injections of the adjuvanted matching placebo.

Treatment:

Biological: Injection Adjuvanted Placebo