Safety and Immunogenicity of an Aluminium Hydroxide/LHD153R Adjuvanted Meningococcal C-CRM197 Conjugate Vaccine

Phase 1

Completed

• Conditions: Infections, Meningococcal
• Interventions: Biological: Investigational MenC-CRM adjuavnted with 50 ug of LHD153R; Biological: Investigational MenC-CRM adjuavnted with 100 ug of LHD153R; Biological: Investigational MenC-CRM adjuavnted with 25 ug of LHD153R; Biological: Investigational MenC-CRM adjuavnted with 12.5 ug of LHD153R; Biological: Meningococcal C-CRM Conjugate Vaccine (MenC-CRM)

• Registration Number: NCT02639351
• Lead Sponsor: GlaxoSmithKline

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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2015-12-21
• Study First Submitted QC: 2015-12-21
• Study First Posted: 2015-12-24
• Study Start: 2016-03-01
• Primary Completion: 2017-08-31
• Study Completion: 2017-08-31
• Results First Submitted: 2018-08-21
• Results First Submitted QC: 2019-03-05
• Status Verified: 2019-06
• Results First Posted: 2019-06-07
• Last Update Submitted: 2019-06-13
• Last Update Posted: 2019-06-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 80

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
LHD153R Formulation 3 Group	Investigational MenC-CRM adjuavnted with 50 ug of LHD153R	Healthy subjects aged 18 to 45 years who received a single dose of investigational MenC-CRM vaccine adjuvanted with 50 ug of LHD153R.
LHD153R Formulation 4 Group	Investigational MenC-CRM adjuavnted with 100 ug of LHD153R	Healthy subjects aged 18 to 45 years who received a single dose of investigational Meningococcal C-CRM conjugate vaccine (MenC-CRM) adjuvanted with 100 ug of LHD153R.
LHD153R Formulation 2 Group	Investigational MenC-CRM adjuavnted with 25 ug of LHD153R	Healthy subjects aged 18 to 45 years who received a single dose of investigational MenC-CRM vaccine adjuvanted with 25 ug of LHD153R.
LHD153R Formulation 1 Group	Investigational MenC-CRM adjuavnted with 12.5 ug of LHD153R	Healthy subjects aged 18 to 45 years who received a single dose of investigational MenC-CRM vaccine adjuvanted with 12.5 ug of LHD153R.
MenC Group	Meningococcal C-CRM Conjugate Vaccine (MenC-CRM)	Healthy subjects aged 18 to 45 years who received a single dose of MenC-CRM vaccine.

Primary Outcome Measures

Name	Time	Method
Number of Subjects With Any Solicited Local and Systemic Adverse Events (AEs)	Within 30 minutes of vaccination (Min) at Day 1	Assessed solicited local symptoms were injection site erythema, induration, pain and swelling. Any erythema/induration/swelling = erythema/induration/swelling spreading beyond 25 millimeters (mm) of injection site. Any pain = occurrence of the symptom regardless of intensity grade. Assessed solicited systemic symptoms were arthralgia, chills, diarrhea, fatigue, fever defined as body temperature greater than or equal to (≥) 38 degrees Celsius (°C), as measured orally, headache, loss of appetite, myalgia, nausea, rash, urticaria and vomiting. Any systemic symptom = occurrence of the symptom regardless of intensity grade.
Number of Subjects With Any Solicited Local and Systemic AEs	From Day 1 to Day 14 (excluding 30 minutes immediately after any vaccination)	Assessed solicited local symptoms were injection site erythema, induration, pain and swelling. Any erythema/induration/swelling = erythema/induration/swelling spreading beyond 25 mm of injection site. Any pain = occurrence of the symptom regardless of intensity grade. Assessed solicited systemic symptoms were arthralgia, chills, diarrhea, fatigue, fever defined as body temperature ≥ 38 °C, as measured orally, headache, loss of appetite, myalgia, nausea, rash, urticaria and vomiting. Any systemic symptom = occurrence of the symptom regardless of intensity grade. Other solicited data included: Analgesic/Antipyretics Use.
Number of Subjects With Any Unsolicited AEs	From Day 1 to Day 29	An adverse event (AE) is defined as any untoward medical occurrence in a subject or clinical investigation subject administered a pharmaceutical product at any dose that does not necessarily have to have a causal relationship with this treatment. Therefore, an AE can be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of an investigational product, whether or not considered related to the investigational product. This definition includes intercurrent illnesses or injuries and exacerbation of pre-existing conditions. Unsolicited adverse event were defined as symptoms that were not solicited using a Subject Diary and that were spontaneously communicated by a subject who has signed the informed consent. Unsolicited AEs were collected through the Day 29 visit and the analysis was performed for Day 1-29 time frame, instead of Day 1-14 as required by protocol.
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).	From Day 1 to Day 366	SAEs are untoward medical occurrences that at any dose resulted in death,was life-threatening,required/prolonged hospitalization,persistent/significant disability/incapacity,congenital anomaly/in important \& significant medical event that could jeopardize the subject/could required intervention to prevent one of the other outcomes mentioned above.MAAEs are AEs that lead to a visit to a healthcare provider.NOCDs are adverse events that represent new diagnosis of a chronic medical condition that was not present/suspected in a subject prior to study enrolment.AESIs were defined according to MedDRA preferred terms.Certain AESIs are monitored after administration of immunostimulatory agents.These are pre-defined \& include AEs in the SOCs of Gastrointestinal disorders,Liver disorders,Metabolic diseases,Musculo-skeletal disorders,Neuroinflammatory disorders,Skin disorders,Vasculitides \& others.
Number of Subjects With Any SAEs, MAAEs, AEs Leading to Study Withdrawal, NOCDs and AESIs.	From Day 29 up to study end (Day 366)	SAEs were defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening, required or prolonged hospitalization, persistent or significant disability/incapacity, congenital anomaly or in an important and significant medical event that could jeopardize the subject or could requiered intervention to prevent one of the other outcomes mentioned above. MAAEs were defined as an AE that lead to a visit to a healthcare provider. NOCDs were defined as AEs leading to study or vaccine withdrawal. AESIs were defined according to MedDRA preferred terms.Certain AEs of special interest (AESIs) are monitored after the administration of immunostimulatory agents. These are pre-defined and include AEs in the SOCs of Gastroin-testinal disorders, Liver disorders, Metabolic diseases, Musculo-skeletal disorders, Neuroinflammatory disorders, Skin disorders, Vasculitides and others
Absolute Values for Clinical Serum Chemistry Parameters- Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST)	At Day 1 (pre-dose)	Analysis was performed on blood samples collected at Day 1 (pre-dose) for the following parameters: ALT and AST in International Units per liter (IU/L).
Changes in Hematology Parameters	At Day 29	Analysis was performed on blood samples collected at Day 29 for the following parameter: HGB in g/L. The change was calculated as difference between the Day 1 (pre-dose) results and the Day 29 results.
Absolute Values for Hematology Parameters- Red Blood Cells (RBC)	At Day 1 (pre-dose)	Analysis was performed on blood samples collected at Day 1 (pre-dose) for the following parameter: RBC in 10\^12 cells per liter (10\^12/L).
Absolute Values for Urinalysis Parameters- Urine Erythrocytes (Urine RBC)	At Day 1 (pre-dose)	Analysis was performed on urine samples collected at Day 1 (pre-dose) for the following parameter: Urine RBC in microliters (μL).
Human Complement Serum Bactericidal Assay (hSBA) Geometric Mean Titers (GMTs) Against N. Meningitidis Serogroup C (MenC)	At Day 1 (pre-dose)	The antibody concentrations were assessed by hSBA directed against MenC serogroup and expressed as GMTs.
Absolute Values for Clinical Serum Chemistry Parameters- Sodium (Na), Potassium (K), Chlorine (Cl), Blood Urea Nitrogen (BUN) and Bicarbonate.	At Day 1 (pre-dose)	Analysis was performed on blood samples collected at Day 1 (pre-dose) for the following parameters: Na, K, Cl, BUN and bicarbonate in millimoles per liter (mmol/L).
Changes in Clinical Serum Chemistry Parameters	At Day 29	Analysis was performed on blood samples collected at Day 29 for the following parameter: CRP in mg/L. The change was calculated as difference between the Day 1 (pre-dose) results and the Day 29 results.
Absolute Values for Clinical Serum Chemistry Parameters-Creatinine	At Day 1 (pre-dose)	Analysis was performed on blood samples collected at Day 1 (pre-dose) for the following parameter: Creatinine (CREA) in micro mole per liter (μmol/L)
Absolute Values for Hematology Parameters- Hematocrit	At Day 1 (pre-dose)	Analysis was performed on blood samples collected at Day 1 (pre-dose) for the following parameter: hematocrit in liter per liter (L/L).
Absolute Values for Urinalysis Parameters- Urine Glucose	At Day 1 (pre-dose)	The absolute value for urinalysis was assessed for the following parameter: urine glucose in mmol/L.
Absolute Values for Clinical Serum Chemistry Parameters- C-reactive Protein (CRP)	At Day 1 (pre-dose)	Analysis was performed on blood samples collected at Day 1 (pre-dose) for the following parameter: CRP in milligram per liter (mg/L).
Absolute Values for Hematology Parameters- Basophils, Eosniophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Plateletes.	At Day 1 (pre-dose)	Analysis was performed on blood samples collected at Day 1 (pre-dose) for the following parameters: basophils, eosinophils, leukocytes, lymphocytes, monocytes, neutrophils and platelets in 10\^9 cells per liter (10\^9/L)
Absolute Values for Hematology Parameters- Hemoglobin (HGB)	At Day 1 (pre-dose)	Analysis was performed on blood samples collected at Day 1 (pre-dose) for the following parameter: HGB in gram per liter (g/L).
Changes in Urinalysis Parameters	At Day 29	Analysis was performed on urine samples collected at day 29 (post-dose) for the following parameter: urine protein in g/L. The change was calculated as difference between the day 1 (pre-dose) results and the day 29 (post-dose) results.
Absolute Values for Urinalysis Parameters- Urine Protein	At Day 1 (pre-dose)	The absolute value for urinalysis was assessed for the following parameter: urine protein in g/L
Number of Subjects With Abnormal Laboratory Parameter Values	At Day 29	The abnormal laboratory parameters values were defined following the FDA CBER Guidance for Industry "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials" dated September 2007, or the institution's normal ranges if they differ from CBER guidance
hSBA GMTs Against N. Meningitidis Serogroup C (MenC)	At Day 29	The antibody concentrations were assessed by hSBA directed against MenC serogroup and expressed as GMTs.
Geometric Mean Ratio (GMR) of the Titers of Antibodies Measured by hSBA Against MenC Serogroup	At Day 29	GMR of GMTs of antibodies against MenC was evaluated at Day 29 relative to Day 1 (pre-dose).

Secondary Outcome Measures

Name	Time	Method
GMR of the GMTs of Antibodies Measured by hSBA Against MenC Serogroup	At Day 8 and Day 181	GMR of GMTs of antibodies against MenC serogroup was evaluated at Day 8 and Day 181 relative to Day 1 (pre-dose).
Percentage of Subjects With hSBA Seroresponse Against N. Meningitidis Serogroup C (MenC).	At Day 8, Day 29 and Day 181	The percentage of subjects who achieved hSBA seroresponse against MenC serogroup was evaluated at Day 8, Day 29 and Day 181 after vaccination. Seroresponse was defined as a post vaccination hSBA ≥ 8 for subjects with a baseline hSBA lower than (\<) 4 or had an increase of at least 4 times the baseline hSBA level for subjects with pre vaccination hSBA ≥ 4.
Percentage of Subjects With at Least a 4-fold Increase in Antibody Concentrations to MenC as Measured by ELISA	At Day 8, Day 29 and Day 181	The percentage of subjects with at least a 4-fold increase in antibody concentrations to MenC serogroup as measured by ELISA were analysed at day 8, 29 and 181 relative to Day 1 (pre-dose).
hSBA GMTs Against N. Meningitidis Serogroup C (MenC)	At Day 8 and Day 181	The antibody concentrations were assessed by hSBA directed against MenC and expressed as GMTs.
Concentrations of Antibodies Against MenC Serogroup Measured by Enzyme Linked Immunosorbent Assay (ELISA)	At Day 1 (pre-dose), Day 8, Day 29 and Day 181	The antibody concentrations were assessed by ELISA and expressed as Geometric Mean Concentrations (GMCs) in microgram per mililiter (μg/mL).

Trial Locations

Locations (1)

GSK Investigational Site; 🇩🇪 Berlin, Germany