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Meningococcal C-CRM Conjugate Vaccine

Phase 1

Infections, Meningococcal | Monoclonal antibody | Other |GSK plc|Last Updated: Jun 28, 2019

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
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Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
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Trial Design
RandomizedACTIVE_CONTROLLEDDMCBiomarker
Total Trials1
Total Enrollment80
FDA Designations
No designations recorded
Clinical Trials (1)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT02639351Safety and Immunogenicity of an Aluminium Hydroxide/LHD153R Adjuvanted Meningococcal C-CRM197 Conjugate VaccinePHASE1 COMPLETED 80Mar 1, 2016Aug 31, 2017Jun 28, 20191 Germany
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Study Endpoints
Primary Endpoints
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 4 (excluding 30 minutes immediately after 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 1 to Day 29

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 Gastrointestinal disorders, Liver disorders, Metabolic diseases, Musculo-skeletal disorders, Neuroinflammatory disorders, Skin disorders, Vasculitides and others

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 1 (post-dose)

Analysis was performed on blood samples collected at Day 1 (post-dose) for the following parameters: Na, K, Cl, BUN and bicarbonate in mmol/L. The change was calculated as difference between the Day 1 (pre-dose) results and the Day 1 (post-dose) 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 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).

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)

Changes in Hematology Parameters
At Day 1 (post-dose)

Analysis was performed on blood samples collected at Day 1 (post-dose) for the following parameters: basophils, eosinophils, leukocytes, lymphocytes, monocytes, neutrophils and platelets in 10\^9/L. The change was calculated as difference between the Day 1 (pre-dose) results and the Day 1 (post-dose) 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 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 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).

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).

Changes in Urinalysis Parameters
At Day 1 (post-dose)

Analysis was performed on urine samples collected at Day 1 (post-dose) for the following parameter: Urine RBC in μL. The change was calculated as difference between the Day 1 (pre-dose) results and the Day 1 (post-dose) results.

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 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 1 (post-dose)

The abnormal laboratory parameters values were classified by the investigator as Normal (a value either low or high at baseline and normal post-baseline), High (a value either normal or low at baseline and high post-baseline), Low (a value either normal or high at baseline and low post-baseline) and No change.

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.

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 Endpoints
hSBA GMTs Against N. Meningitidis Serogroup C (MenC)
At Day 8 and Day 181
GMR of the GMTs of Antibodies Measured by hSBA Against MenC Serogroup
At Day 8 and Day 181
Percentage of Subjects With hSBA Seroresponse Against N. Meningitidis Serogroup C (MenC).
At Day 8, Day 29 and Day 181
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Study Design & Arms
AllocationRANDOMIZED
MaskingSINGLE
ModelPARALLEL
PurposePREVENTION
Treatment Arms
ArmTypeDescription
LHD153R Formulation 1 GroupEXPERIMENTALHealthy subjects aged 18 to 45 years who received a single dose of investigational MenC-CRM vaccine adjuvanted with 12.5 ug of LHD153R.
LHD153R Formulation 2 GroupEXPERIMENTALHealthy subjects aged 18 to 45 years who received a single dose of investigational MenC-CRM vaccine adjuvanted with 25 ug of LHD153R.
LHD153R Formulation 3 GroupEXPERIMENTALHealthy 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 GroupEXPERIMENTALHealthy 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.
MenC GroupACTIVE_COMPARATORHealthy subjects aged 18 to 45 years who received a single dose of MenC-CRM vaccine.
Interventions
NameTypeDescription
Investigational MenC-CRM adjuavnted with 12.5 ug of LHD153RBIOLOGICALIntramuscular (IM) vaccination of 1 dose of 0.5 mL
Investigational MenC-CRM adjuavnted with 25 ug of LHD153RBIOLOGICALIM vaccination of 1 dose of 0.5 mL
Investigational MenC-CRM adjuavnted with 50 ug of LHD153RBIOLOGICALIM vaccination of 1 dose of 0.5 mL
Investigational MenC-CRM adjuavnted with 100 ug of LHD153RBIOLOGICALIM vaccination of 1 dose of 0.5 mL
Meningococcal C-CRM Conjugate Vaccine (MenC-CRM)BIOLOGICALIM vaccination of 1 dose of 0.5 mL
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Eligibility Criteria
Age Range18 Years — 45 Years
SexALL
Healthy VolunteersYes
Study Sites1

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 b...

Countries:Germany
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