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

NCT04602975 | Completed Phase 2 DMC

• 1 other identifier: 2018-017
• Study Type: interventional
• Target: 248
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy

Keywords

vaccine; anti-shigella; shigella; diarrheic disease; Kenya

Outcome Measures

Primary Outcomes (2)

• Number, proportion,severity and relatedness of adverse events (AEs) to measure the safety and tolerability of SF2a-TT15 vaccine (2 μg OS and 10 μg OS) in each cohort.

  Solicited reactions, AEs, SAEs assessed post-vaccination using targeted physical examinations, vital signs, and clinical laboratory tests

  15 months

• Analyses of the serum anti-S. flexneri 2a lipopolysaccharide (LPS) IgG antibody response in the infant target population to assess the immunogenicity of the vaccine.

  Proportion of responders (4-fold increases over baseline) in serum anti-S. flexneri 2a LPS IgG antibody response

  15 months

Secondary Outcomes (3)

• The number and proportion of responders, the geometric mean titer (GMT), mean fold-rises (compared to baseline), and peak-post-vaccination of the serum bactericidal activity (SBA) antibody (functionality of SF2a-specific IgGs antibodies in infants).

  15 months

• Analyses of the serum anti-S. flexneri 2a LPS Immunoglobulins G (IgG) antibody response in the adult and children cohorts.

  15 months

• Comparison of the Measle-Rubella (MR) vaccine immune response in SF2a-TT15 vaccinees and placebo groups for the infant cohort.

  15 months

Study Arms (12)

Adults cohort 1 vaccinees

EXPERIMENTAL

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.

Biological: Injection SF2A-TT15 10 µg Adjuvanted

Adults cohort 1 placebo recipients

PLACEBO COMPARATOR

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

Biological: Injection Adjuvanted Placebo

Children cohort 2 vaccinees

EXPERIMENTAL

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.

Biological: Injection SF2A-TT15 10 µg Adjuvanted

Children cohort 2 placebo recipients

PLACEBO COMPARATOR

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

Biological: Injection Adjuvanted Placebo

Infants cohort 3A vaccinees (-)

EXPERIMENTAL

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.

Biological: Injection SF2A-TT15 2 µg

Infants cohort 3A placebo recipients (-)

PLACEBO COMPARATOR

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

Biological: Injection Placebo

Infants cohort 3A vaccinees (+)

EXPERIMENTAL

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.

Biological: Injection SF2A-TT15 2 µg Adjuvanted

Infants cohort 3A placebo recipients (+)

PLACEBO COMPARATOR

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

Biological: Injection Adjuvanted Placebo

Infants cohort 3B vaccinees (-)

EXPERIMENTAL

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.

Biological: Injection SF2A-TT15 10 µg

Infants cohort 3B placebo recipients (-)

PLACEBO COMPARATOR

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

Biological: Injection Placebo

Infants cohort 3B vaccinees (+)

EXPERIMENTAL

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.

Biological: Injection SF2A-TT15 10 µg Adjuvanted

Infants cohort 3B placebo recipients (+)

PLACEBO COMPARATOR

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

Biological: Injection Adjuvanted Placebo

Interventions

Injection SF2A-TT15 10 µg Adjuvanted BIOLOGICAL

Intramuscular injection of experimental vaccine (adjuvanted 10 µg)

Also known as: SF2A-TT15 10 µg Adjuvanted, Anti-shigella experimental vaccine (10µg with alhydrogel)

Adults cohort 1 vaccinees; Children cohort 2 vaccinees; Infants cohort 3B vaccinees (+)

Injection SF2A-TT15 10 µg BIOLOGICAL

Intramuscular injection of experimental vaccine (not adjuvanted 10 µg)

Also known as: SF2A-TT15 10 µg not adjuvanted, Anti-shigella experimental vaccine (10µg without alhydrogel)

Infants cohort 3B vaccinees (-)

Injection Adjuvanted Placebo BIOLOGICAL

Intramuscular injection of Placebo with alhydrogel

Also known as: Placebo with Alhydrogel injection

Adults cohort 1 placebo recipients; Children cohort 2 placebo recipients; Infants cohort 3A placebo recipients (+); Infants cohort 3B placebo recipients (+)

Injection Placebo BIOLOGICAL

Intramuscular injection of the not adjuvanted Placebo

Also known as: Placebo without alhydrogel injection

Infants cohort 3A placebo recipients (-); Infants cohort 3B placebo recipients (-)

Injection SF2A-TT15 2 µg Adjuvanted BIOLOGICAL

Intramuscular injection of experimental vaccine (adjuvanted 2 µg)

Also known as: SF2A-TT15 2 µg Adjuvanted, Anti-shigella experimental vaccine (2µg with alhydrogel)

Infants cohort 3A vaccinees (+)

Injection SF2A-TT15 2 µg BIOLOGICAL

Intramuscular injection of experimental vaccine (not adjuvanted 2 µg)

Also known as: SF2A-TT15 2 µg not adjuvanted, Anti-shigella experimental vaccine (2µg without alhydrogel)

Infants cohort 3A vaccinees (-)

Eligibility Criteria

• Age: 8 Months - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• For adults:
• Healthy men and women between 18 and 50 (inclusive) years of age.
• Subjects who provide written informed consent or thumb print in the presence of a witness to participate in the study
• 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:
• Healthy boys and girls between 2 and 5 years of age for the children group (cohort 2)
• Healthy boys and girls 9 mo-old (+/- 1 month) for the infant group (cohort 3)
• Parents or legally acceptable representatives, as appropriate, who are willing and able to provide signed/thumb printed informed consent for children and infants.
• 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:
• 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.
• Subjects in general good health in the opinion of the Investigator as determined by medical history, vital signs and a physical examination.
• No clinically significant abnormalities in hematology, blood chemistry, or urinalysis laboratory tests at screening.
• Negative HIV, Hepatitis B and Hepatitis C serology tests and malaria test.

You may not qualify if:

• Subjects with a history of clinically significant gastrointestinal disorders (e.g. gastroesophageal reflux disease, peptic ulcer, celiac disease, inflammatory bowel disease).
• Individuals with immunosuppressive diseases or under immunosuppressive therapy.
• Previous participation in any study in which a Shigella-vaccine candidate was administered.
• 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.
• 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.
• 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.
• 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.
• Participation in another clinical trial with drugs within 3 months prior first study injection.

Sponsors & Collaborators

• Institut Pasteur: lead
• Wellcome Trust: collaborator
• Gates Medical Research Institute: collaborator
• Henry M. Jackson Foundation Medical Research International: collaborator
• Walter Reed Army Institute of Research (WRAIR): collaborator
• Parexel: collaborator
• ClinWin Research: collaborator

Study Sites (1)

KEMRI / Henry M. Jackson Foundation Medical Research International

Kericho, Kenya

Location

MeSH Terms

Conditions

Dysentery, Bacillary

Interventions

Aluminum Hydroxide

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

Intervention Hierarchy (Ancestors)

Hydroxides; Alkalies; Inorganic Chemicals; Aluminum Compounds; Anions; Ions; Electrolytes

Study Officials

• Armelle Phalipon, PhD

  Institut Pasteur

  STUDY CHAIR

• Laurence Mulard, PhD

  Institut Pasteur

  STUDY CHAIR

• Christiane Gerke, PhD

  Institut Pasteur (Consulting)

  STUDY CHAIR

• Fredrick Sawe, MBChB MMED

  Kenya Medical Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Every team will be masked except the pharmacist and the pharmacy team on site and one dedicated personal within Sponsor team.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized, age descending (3 cohorts), with dose escalation in the target cohort

Study Record Dates

• First Submitted: September 24, 2020
• First Posted: October 26, 2020
• Study Start: October 6, 2020
• Primary Completion: April 12, 2023
• Study Completion: November 15, 2023
• Last Updated: April 23, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

KE (1)