Phase 1 N=140 Randomized Quadruple-blind Prevention

Safety and Immunogenicity Study of GSK's Clostridium Difficile Vaccine 2904545A When Administered in Healthy Adults Aged 18-45 Years and 50-70 Years

Clostridium Infections

Bottom Line

View on ClinicalTrials.gov: NCT04026009 ↗

Enrolled (actual)

140

Serious AEs

5.0%

Results posted

Sep 2024

Primary outcome: Primary: Number of Subjects With Any and Grade 3 Solicited Local Symptoms, After Each Vaccine Dose — 0; 0; 0; 8 Participants

Study Design & Population

Study type: Interventional
Phase: Phase 1
Interventions: C. difficile investigational vaccine based on the F2 antigen (GSK2904545A) (Biological); C. difficile investigational vaccine based on the F2 antigen (GSK2904545A) adjuvanted with AS01B (Biological); Placebo (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: GlaxoSmithKline
Primary completion: May 2022

Outcome Measures

Outcome	Result	p-value
PRIMARY Number of Subjects With Any and Grade 3 Solicited Local Symptoms, After Each Vaccine Dose	0; 0; 0; 8; 0; 0	—
PRIMARY Number of Subjects With Any, Grade 3, Related and Grade 3 Related Solicited General Symptoms, After Each Vaccine Dose	0; 0; 0; 5; 3; 0	—
PRIMARY Number of Subjects With Any, Grade 3, Related, Grade 3 Related and Medically Attended Unsolicited Adverse Events (AEs)	3; 2; 22; 27; 11; 1	—
PRIMARY Number of Subjects With Serious Adverse Events (SAEs)	0; 1; 3; 3; 0	—
PRIMARY Number of Subjects With Potential Immune-mediated Diseases (pIMDs)	0; 0; 2; 0; 0	—
PRIMARY Number of Subjects With Hematological, Biochemical, and Urinary Laboratory Abnormalities at Screening	0; 0; 3; 1; 0; 0	—
PRIMARY Number of Subjects With Hematological and Biochemical Laboratory Abnormalities at Day 8	0; 0; 2; 1; 0; 0	—
PRIMARY Number of Subjects With Hematological and Biochemical Laboratory Abnormalities at Day 31	0; 0; 2; 3; 0; 0	—
PRIMARY Number of Subjects With Hematological and Biochemical Laboratory Abnormalities at Day 38	0; 0; 0; 2; 1; 0	—
PRIMARY Number of Subjects With Hematological and Biochemical Laboratory Abnormalities at Day 180	0; 1; 2; 2; 0; 0	—
PRIMARY Number of Subjects With Hematological and Biochemical Laboratory Abnormalities at Day 390	0; 0; 2; 0; 1; 0	—
PRIMARY Number of Subjects With Hematological and Biochemical Laboratory Abnormalities at Day 476	0; 0; 1; 0; 0; 0	—
PRIMARY Number of Subjects With Hematological and Biochemical Laboratory Abnormalities at Day 491	0; 0; 1; 1; 0; 0	—
PRIMARY Number of Subjects With Hematological and Biochemical Laboratory Abnormalities at Day 670	0; 0; 2; 1; 0; 0	—
SECONDARY Serum Neutralizing Anti-Toxin A and Anti-Toxin B Antibody Titers, as Measured by Toxin Neutralization Assay (TNA)	7.24; 6.00; 6.00; 6.64; 6.25; 55.52	—

Summary

The purpose of this study is to generate safety, reactogenicity (assessment of any expected or unexpected side effect of the vaccine) and immunogenicity (ability to induce an immune response) data for the development of a candidate Clostridium difficile (C. difficile) vaccine that would protect against primary cases of Clostridium difficile infection (CDI) and CDI recurrence. Clostridium difficile infection is a major cause of gastrointestinal illness with approximately 500,000 infections and the leading cause of gastroenteritis associated death with 29,000 deaths annually in the United States of America (USA). The emergence of extremely infectious varieties/types of C. difficile has contributed to increase the number and severity of CDI cases. In recent years, some countries (United Kingdom) have implemented hospital hygiene and other measures which resulted in significant reductions in the number of cases. The burden is, however, expected to remain significant until vaccination is available.

Eligibility Criteria

Inclusion Criteria

Subjects who, in the opinion of the Investigator, can and will comply with the requirements of the protocol.
Written or witnessed/thumb print informed consent obtained from the subject prior to performance of any study specific procedure.
For Step 1 only: A male or female between, and including, 18-45 years of age at the time of the first vaccination.
For Steps 2, 3, and 4: A male or female between, and including, 50-70 years of age at the time of the first vaccination.
Healthy subjects as established by medical history and clinical examination before entering into the study.
Subjects free of any uncontrolled chronic illnesses as established by medical history and clinical examination before entering into the study.
Female subjects of non-childbearing potential may be enrolled in the study.
Non-childbearing potential is defined as premenarche, current bilateral tubal ligation or occlusion, hysterectomy, bilateral ovariectomy, or post-menopause.

Female subjects of childbearing potential may be enrolled in the study, if the subject:

Has practiced adequate contraception for 30 days prior to vaccination, and
Has a negative urine pregnancy test on the day of vaccination, and
Has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the vaccination series.

Exclusion Criteria

Health condition that, in the opinion of the Investigator, may interfere with optimal participation in the study or place the volunteer at increased risk of AEs. Study clinicians, in consultation with the Principal Investigator will use clinical judgment on a case by case basis to assess safety risks under this criterion. The Principal Investigator will consult with the Medical Monitor as appropriate.
Use of any investigational or nonregistered product other than the study vaccine(s) during the period starting 30 days before the first dose of study vaccine(s) (Day 29 to Day 1), or planned use during the study period.
Any medical condition that in the judgment of the Investigator would make IM injection unsafe and subjects under treatment with anticoagulant therapy.
Chronic administration of immunosuppressants or other immune modifying drugs during the period starting 3 months prior to the first vaccination. For corticosteroids, this will mean prednisone ≥ 5 milligrams per day (mg/day) (for adult subjects), or equivalent. Inhaled and topical steroids are allowed.
Administration of long acting immune modifying drugs at any time during the study period.
Administration of immunosuppressive therapy, including chemotherapeutic agents used to treat cancer or other conditions, and treatments associated with organ or bone marrow transplantation or autoimmune disease.
Administration of immunoglobulins and/or any blood products during the period starting 3 months before the first vaccination of study treatment or planned administration during the study period.
Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting 6 weeks before the first vaccination and ending 6 weeks after the last vaccination, with the exception of inactivated influenza vaccine which can be administered up to 14 days before or from 30 days after the last study vaccination.

In case an emergency mass vaccination for an unforeseen public health threat (eg, a pandemic) is recommended and/or organized by public health authorities outside the routine immunization program, the time period described above can be reduced if, necessary for that vaccine, provided it is used according to the local governmental recommendations and that the Sponsor is notified accordingly.

Planned administration of GSK's Herpes Zoster vaccine marketed as Shingrix or an adjuvanted recombinant varicella zoster virus envelope gE subunit vaccine (HZ/su) within 180 days before the first dose and within 180 days after the last dose of the study

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT04026009). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.