Clinical trial NCT02639351: Safety and Immunogenicity of an Aluminium Hydroxide/LHD153R Adjuvanted Meningococcal C-CRM197 Conjugate Vaccine
Official title: A Phase 1, Randomized, Observer-Blind, Dosage-Escalation Study to Evaluate the Safety and Immunogenicity of an Aluminium Hydroxide/LHD153R Adjuvanted Meningococcal C-CRM197 Conjugate Vaccine Compared to Aluminium Hydroxide Adjuvanted Meningococcal C-CRM197 Conjugate Vaccine in Healthy Adults (18-45 Years of Age).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Infections, Meningococcal
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2015-12-24
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Dosage-Escalation Study to Evaluate the Safety and Immunogenicity of an Aluminium Hydroxide/LHD153R Adjuvanted Meningococcal C-CRM197 Conjugate Vaccine in Healthy Adults (18-45 years of age).


Eligibility criteria: Inclusion Criteria:

1. Male or female individuals of 18 through 45 years of age on the day of informed consent
2. Healthy volunteers with good physical and mental health status, determined on the basis of the medical history, a physical examination and the results of the screening tests as judged by the investigator
3. Individuals who have voluntarily given written informed consent after the nature of the study has been explained according to local regulatory requirements, prior to study entry
4. Individuals who can comply with study procedures including follow-up
5. Individuals that are able to understand, read and write German language
6. Females of childbearing potential who are using an effective birth control method which they intend to use for at least 30 days after the study vaccination.

Exclusion Criteria:

1. Progressive, unstable or uncontrolled clinical conditions
2. Hypersensitivity, including allergy, to any component of vaccines, medicinal products or medical equipment whose use is foreseen in this study
3. Clinical conditions representing a contraindication to intramuscular vaccination and blood draws
4. Abnormal function of the immune system
5. Received immunoglobulins or any blood products within 180 days prior to informed consent
6. Received an investigational or non-registered medicinal product within 30 days prior to informed consent or intend to participate in another clinical study at any time during the conduct of this study
7. Vulnerable subjects (e.g. persons kept in detention), study personnel or an immediate family or household member of study personnel, subjects with legal incapacity or limited legal capacity
8. Any relevant deviation from the laboratory parameters at screening as judged by the investigator
9. Previously received any vaccine that included a MenC antigen
10. Previously suspected or confirmed disease caused by N. meningitides
11. Had household contact with and/or intimate exposure to an individual with culture proven MenC
12. A positive serum or urine pregnancy test prior to the study vaccine administration or are currently lactating.
13. A positive drugs-of-abuse test prior to the study vaccine administration;
14. Received any other vaccines within 30 days prior to enrolment in this study or who are planning to receive any vaccine within 30 days from the administration of study vaccines
15. Any other condition that, in the opinion of the investigator, might interfere with the results of the study or pose additional risk to the subject due to participation in the study.

Primary outcomes:
measure: Number of Subjects With Any Solicited Local and Systemic Adverse Events (AEs)
timeFrame: Within 30 minutes of vaccination (Min) at Day 1
measure: Number of Subjects With Any Solicited Local and Systemic AEs
timeFrame: From Day 1 to Day 4 (excluding 30 minutes immediately after vaccination)
measure: Number of Subjects With Any Solicited Local and Systemic AEs
timeFrame: From Day 5 to Day 8
measure: Number of Subjects With Any Solicited Local and Systemic AEs
timeFrame: From Day 8 to Day 14
measure: Number of Subjects With Any Solicited Local and Systemic AEs
timeFrame: From Day 1 to Day 8 (excluding 30 minutes immediately after vaccination)
measure: Number of Subjects With Any Solicited Local and Systemic AEs
timeFrame: From Day 1 to Day 14 (excluding 30 minutes immediately after any vaccination)
measure: Number of Subjects With Any Unsolicited AEs
timeFrame: From Day 1 to Day 29
measure: Number of Subjects With Any Serious Adverse Events (SAEs), Medically Attended AEs (MAAEs), AEs Leading to Study Withdrawal, New Onset of Chronic Disease (NOCDs) and Adverse Events of Special Interest (AESIs).
timeFrame: From Day 1 to Day 366
measure: Number of Subjects With Any SAEs, MAAEs, AEs Leading to Study Withdrawal, NOCDs and AESIs.
timeFrame: From Day 1 to Day 29
measure: Number of Subjects With Any SAEs, MAAEs, AEs Leading to Study Withdrawal, NOCDs and AESIs.
timeFrame: From Day 29 up to study end (Day 366)
measure: Absolute Values for Clinical Serum Chemistry Parameters- Sodium (Na), Potassium (K), Chlorine (Cl), Blood Urea Nitrogen (BUN) and Bicarbonate.
timeFrame: At Day 1 (pre-dose)
measure: Changes in Clinical Serum Chemistry Parameters
timeFrame: At Day 1 (post-dose)
measure: Changes in Clinical Serum Chemistry Parameters
timeFrame: At Day 8
measure: Changes in Clinical Serum Chemistry Parameters
timeFrame: At Day 29
measure: Absolute Values for Clinical Serum Chemistry Parameters-Creatinine
timeFrame: At Day 1 (pre-dose)
measure: Changes in Clinical Serum Chemistry Parameters
timeFrame: At Day 1 (post-dose)
measure: Changes in Clinical Serum Chemistry Parameters
timeFrame: At Day 8
measure: Changes in Clinical Serum Chemistry Parameters
timeFrame: At Day 29
measure: Absolute Values for Clinical Serum Chemistry Parameters- Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST)
timeFrame: At Day 1 (pre-dose)
measure: Changes in Clinical Serum Chemistry Parameters
timeFrame: At Day 1 (post-dose)
measure: Changes in Clinical Serum Chemistry Parameters
timeFrame: At Day 8
measure: Changes in Clinical Serum Chemistry Parameters
timeFrame: At Day 29
measure: Absolute Values for Clinical Serum Chemistry Parameters- C-reactive Protein (CRP)
timeFrame: At Day 1 (pre-dose)
measure: Changes in Clinical Serum Chemistry Parameters
timeFrame: At Day 1 (post-dose)
measure: Changes in Clinical Serum Chemistry Parameters
timeFrame: At Day 8
measure: Changes in Clinical Serum Chemistry Parameters
timeFrame: At Day 29
measure: Absolute Values for Hematology Parameters- Basophils, Eosniophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Plateletes.
timeFrame: At Day 1 (pre-dose)
measure: Changes in Hematology Parameters
timeFrame: At Day 1 (post-dose)
measure: Changes in Hematology Parameters
timeFrame: At Day 8
measure: Changes in Hematology Parameters
timeFrame: At Day 29
measure: Absolute Values for Hematology Parameters- Red Blood Cells (RBC)
timeFrame: At Day 1 (pre-dose)
measure: Changes in Hematology Parameters
timeFrame: At Day 1 (post-dose)
measure: Changes in Hematology Parameters
timeFrame: At Day 8
measure: Changes in Hematology Parameters
timeFrame: At Day 29
measure: Absolute Values for Hematology Parameters- Hematocrit
timeFrame: At Day 1 (pre-dose)
measure: Changes in Hematology Parameters
timeFrame: At Day 1 (post-dose)
measure: Changes in Hematology Parameters
timeFrame: At Day 8
measure: Changes in Hematology Parameters
timeFrame: At Day 29
measure: Absolute Values for Hematology Parameters- Hemoglobin (HGB)
timeFrame: At Day 1 (pre-dose)
measure: Changes in Hematology Parameters
timeFrame: At Day 1 (post-dose)
measure: Changes in Hematology Parameters
timeFrame: At Day 8
measure: Changes in Hematology Parameters
timeFrame: At Day 29
measure: Absolute Values for Urinalysis Parameters- Urine Erythrocytes (Urine RBC)
timeFrame: At Day 1 (pre-dose)
measure: Changes in Urinalysis Parameters
timeFrame: At Day 1 (post-dose)
measure: Changes in Urinalysis Parameters
timeFrame: At Day 8
measure: Changes in Urinalysis Parameters
timeFrame: At Day 29
measure: Absolute Values for Urinalysis Parameters- Urine Glucose
timeFrame: At Day 1 (pre-dose)
measure: Changes in Urinalysis Parameters
timeFrame: At Day 1 (post-dose)
measure: Changes in Urinalysis Parameters
timeFrame: At Day 8
measure: Changes in Urinalysis Parameters
timeFrame: At Day 29
measure: Absolute Values for Urinalysis Parameters- Urine Protein
timeFrame: At Day 1 (pre-dose)
measure: Changes in Urinalysis Parameters
timeFrame: At Day 1 (post-dose)
measure: Changes in Urinalysis Parameters
timeFrame: At Day 8
measure: Changes in Urinalysis Parameters
timeFrame: At Day 29
measure: Number of Subjects With Abnormal Laboratory Parameter Values
timeFrame: At Day 1 (post-dose)
measure: Number of Subjects With Abnormal Laboratory Parameter Values
timeFrame: At Day 8
measure: Number of Subjects With Abnormal Laboratory Parameter Values
timeFrame: At Day 29
measure: Number of Subjects With Abnormal Laboratory Parameter Values
timeFrame: At Day 1 (post-dose)
measure: Number of Subjects With Abnormal Laboratory Parameter Values
timeFrame: At Day 8
measure: Number of Subjects With Abnormal Laboratory Parameter Values
timeFrame: At Day 29
measure: Human Complement Serum Bactericidal Assay (hSBA) Geometric Mean Titers (GMTs) Against N. Meningitidis Serogroup C (MenC)
timeFrame: At Day 1 (pre-dose)
measure: hSBA GMTs Against N. Meningitidis Serogroup C (MenC)
timeFrame: At Day 29
measure: Geometric Mean Ratio (GMR) of the Titers of Antibodies Measured by hSBA Against MenC Serogroup
timeFrame: At Day 29
Secondary outcomes:
measure: hSBA GMTs Against N. Meningitidis Serogroup C (MenC)
timeFrame: At Day 8 and Day 181
measure: GMR of the GMTs of Antibodies Measured by hSBA Against MenC Serogroup
timeFrame: At Day 8 and Day 181
measure: Percentage of Subjects With hSBA Seroresponse Against N. Meningitidis Serogroup C (MenC).
timeFrame: At Day 8, Day 29 and Day 181
measure: Concentrations of Antibodies Against MenC Serogroup Measured by Enzyme Linked Immunosorbent Assay (ELISA)
timeFrame: At Day 1 (pre-dose), Day 8, Day 29 and Day 181
measure: Percentage of Subjects With at Least a 4-fold Increase in Antibody Concentrations to MenC as Measured by ELISA
timeFrame: At Day 8, Day 29 and Day 181
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Gonzalez-Lopez A, Oostendorp J, Koernicke T, Fadini T, D'Oro U, Baker S, O'Hagan DT, Del Giudice G, Siena E, Finco O, Medini D. Adjuvant effect of TLR7 agonist adsorbed on aluminum hydroxide (AS37): A phase I randomized, dose escalation study of an AS37-adjuvanted meningococcal C conjugated vaccine. Clin Immunol. 2019 Dec;209:108275. doi: 10.1016/j.clim.2019.108275. Epub 2019 Oct 24.