A Reactogenicity, Safety and Immunogenicity Study of GSK's Paediatric Herpes Zoster Subunit Candidate Vaccine (PED-HZ/su) GSK143713A in Immunocompromised Paediatric Renal Transplant Recipients
Overview
- Phase
- Phase 1
- Intervention
- PED-HZ/su
- Conditions
- Herpes Zoster
- Sponsor
- GlaxoSmithKline
- Enrollment
- 184
- Locations
- 1
- Primary Endpoint
- Number of subjects from the control groups with solicited general symptoms
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
The purpose of this study is to evaluate the reactogenicity, safety and immunogenicity of 2 doses of PED-HZ/su, GSK's vaccine candidate for the prevention of Herpes Zoster (HZ) in immunocompromised paediatric renal transplant recipients aged 1-17 years
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subjects' parent(s)/Legally Acceptable Representative(s) \[LAR(s) who, in the opinion of the investigator, can and will comply, with the requirements of the protocol
- •Written or witnessed/thumb printed informed consent obtained from the parent(s)/LAR(s) of the subject prior to performance of any study specific procedure.
- •Written informed assent obtained from the subjects when applicable according to local requirements.
- •A male or female between, and including, 1 and 17 years of age at the time of randomisation (Visit Day 1)
- •Body weight ≥ 6 kg/13.23 pounds.
- •A subject is eligible if they meet at least one of the following criteria:
- •Documented previous VZV vaccination OR
- •Medically verified varicella (with source documentation) OR
- •Seropositive for VZV prior to transplantation.
- •Subjects with renal transplant more than six months (180 days) prior randomization (Visit Day 1)
Exclusion Criteria
- •Medical conditions
- •Any primary kidney disease with a high incidence of recurrent primary kidney disease within the allograft
- •Evidence of recurrent primary kidney disease within the current allograft
- •Previous allograft loss secondary to recurrent primary kidney disease
- •History of more than one organ transplanted (that is, kidney-liver, simultaneous double kidney or kidney-other organ(s) transplanted).
- •Subjects with an episode of acute allograft rejection over the six months (180 days) prior to enrolment
- •Panel Reactive Antibodies (PRA) calculated PRA (cPRA) or Calculated Reaction Frequency (cRF) score that is unknown at the time of transplant
- •VZV serostatus unknown prior to transplant
- •Subjects with advanced chronic kidney disease
- •Evidence of significant proteinuria (≥ 200 g/mol creatinine) believed to be of renal origin (an example of non-renal origin is proteinuria from mucus in a reconstructed bladder)
Arms & Interventions
PED-HZ/su 12-17 Group
Paediatric renal transplant recipients aged 12 to 17 years old, receiving 2 doses of the investigational vaccine (PED HZ/su)
Intervention: PED-HZ/su
PED-HZ/su 1-11 Group
Paediatric renal transplant recipients aged 1 to 11 years old, receiving 2 doses of the investigational vaccine (PED HZ/su). Enrolment into this group will be in a staggered manner. Following enrolment into the PED-HZ/su 12-17 group, a safety evaluation of data collected up to visit month 2 will be performed. Upon favourable outcome of the evaluation, enrolment into this group will begin.
Intervention: PED-HZ/su
Outcomes
Primary Outcomes
Number of subjects from the control groups with solicited general symptoms
Time Frame: Within 7 days after Visit Month 1
Assessed solicited general symptoms among Infants/Toddlers/Children \< 6 years are: * Drowsiness * Fever\* * Irritability/Fussiness * Loss of appetite * GI symptoms\*\* Assessed solicited general symptoms among Children ≥ 6 years are: * Fatigue * Fever\* * GI symptoms\*\* * Headache * Myalgia * Shivering (chills) * Fever is defined as temperature ≥ 38.0°C/100.4°F \*\*GI symptoms include nausea, vomiting, diarrhoea, and/or abdominal pain
Number of subjects from the interventional groups with unsolicited AEs after each vaccination
Time Frame: Within 30 days after each vaccination (vaccines administered on day 1 and month 1)
An unsolicited AE is any AE reported in addition to those solicited during the clinical study. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms is to be reported as an unsolicited adverse event.
Number of subjects from the interventional groups, with solicited general AEs
Time Frame: Within 7 days after each vaccination (vaccines administered on day 1 and month 1)
Assessed solicited general AEs among Infants/Toddlers/Children \< 6 years are: * Drowsiness * Fever\* * Irritability/Fussiness * Loss of appetite * Gastrointestinal (GI) symptoms\*\* Assessed solicited general AEs among Children ≥ 6 years are: * Fatigue * Fever\* * GI symptoms\*\* * Headache * Myalgia * Shivering (chills) * Fever is defined as temperature ≥ 38.0°C/100.4°F \*\*GI symptoms include nausea, vomiting, diarrhoea, and/or abdominal pain Note: GSK diary cards for collecting solicited local and general AEs/symptoms is different for subjects \< 6 years and ≥ 6 years. Hence the age category of 1-11 years is further split to 1-5 years and 6-11 years.
Number of subjects from the control groups with unsolicited symptoms
Time Frame: Within 30 days after Visit Month 1
An unsolicited symptom is any symptom reported in addition to those solicited during the clinical study. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms is to be reported as an unsolicited adverse event.
Number of subjects with serious adverse events (SAEs), potential immune mediated diseases (pIMDs) and biopsy confirmed renal allograft rejection.
Time Frame: From Visit Day 1 up to Visit Month 2
An SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization or results in disability/incapacity. pIMDs are sub sets of Adverse events of special interest (AESIs) that include autoimmune disease and other inflammatory and/neurological disorders of interest, which may or may not have autoimmune aetiology. The renal allograft rejections are biopsy confirmed pathophysiological changes indicative of rejection. The rejection is graded for severity and extent of histologic inflammation and injury. The reporting period for any renal allograft rejection is from Visit Day 1 to the study end (month 2).
Percentage of subjects with Anti-gE antibody concentrations in terms of Geometric Mean Concentrations (GMCs)
Time Frame: At Month 2 (one-month post-dose 2)
The geometric mean concentration (GMC) calculations are performed by taking the anti log of the mean of the log concentration transformations. Antibody concentrations below the cut-off of the assay will be given an arbitrary value equal to half the cut-off for GMC calculation
Number of subjects from the non-interventional groups with seizures
Time Frame: Within 30 days after Visit Month 1
All seizures occurring within 30 days of visit month 1 are reported, for the control groups
Number of subjects from the interventional groups, with solicited local adverse events (AEs)
Time Frame: Within 7 days after each vaccination (vaccines administered on day 1 and month 1)
Assessed solicited local AEs are pain, redness and swelling at the injection site. Pain includes tenderness. Note: GSK diary cards for collecting solicited local and general AEs/symptoms is different for subjects \< 6 years and ≥ 6 years. Hence the age category of 1-11 years is further split to 1-5 years and 6-11 years.
Number of subjects from the interventional groups with seizures
Time Frame: Within 30 days after each vaccination (vaccines administered on day 1 and month 1)
All seizures occurring within 30 days following study vaccination are reported.
Number of subjects from the interventional groups with generalized convulsive seizures
Time Frame: Within 7 days after each vaccination (vaccines administered on day 1 and month 1)
Generalized convulsive seizures are classified as follows: * Level 1 of diagnostic certainty: witnessed sudden loss of consciousness AND generalized, tonic, clonic, tonic-clonic, or atonic motor manifestations * Level 2 of diagnostic certainty: history of unconsciousness AND generalized, tonic, clonic, tonic-clonic, or atonic motor manifestations * Level 3 of diagnostic certainty: history of unconsciousness AND other generalized motor manifestations * Level 4 of diagnostic certainty: reported generalized convulsive seizure with insufficient evidence to meet the case definitions for Level 1, 2 or 3 of diagnostic certainty above * Level 5 of diagnostic certainty: Not a case of generalized convulsive seizure Only levels 1 to 3 of generalized convulsive seizures will comprise the analysis for this outcome measure.
Number of subjects from the non-interventional groups with generalized convulsive seizures
Time Frame: Within 7 days after Visit Month 1
Generalized convulsive seizures are classified as follows: * Level 1 of diagnostic certainty: witnessed sudden loss of consciousness AND generalized, tonic, clonic, tonic-clonic, or atonic motor manifestations * Level 2 of diagnostic certainty: history of unconsciousness AND generalized, tonic, clonic, tonic-clonic, or atonic motor manifestations * Level 3 of diagnostic certainty: history of unconsciousness AND other generalized motor manifestations * Level 4 of diagnostic certainty: reported generalized convulsive seizure with insufficient evidence to meet the case definitions for Level 1, 2 or 3 of diagnostic certainty above * Level 5 of diagnostic certainty: Not a case of generalized convulsive seizure Only levels 1 to 3 of generalized convulsive seizures will comprise the analysis for this outcome measure
Secondary Outcomes
- Number of subjects from the interventional pooled age group with unsolicited AEs after each vaccination(Within 30 days after each vaccination (vaccines administered on day 1 and month 1))
- Number of subjects from the non-interventional pooled age group with unsolicited symptoms(Within 30 days after Visit Month 1)
- Number of subjects with SAEs, pIMDs and biopsy confirmed renal allograft rejections from day 1 to month 13(From Visit Day 1 up to Visit Month 13)
- Number of subjects from the interventional pooled age group with solicited local AEs(Within 7 days after each vaccination (vaccines administered on day 1 and month 1))
- Number of subjects from the interventional pooled age group with solicited general AEs(Within 7 days after each vaccination (vaccines administered on day 1 and month 1))
- Number of subjects from the non-interventional pooled age group with solicited general symptoms(Within 7 days after each vaccination (vaccines administered on day 1 and month 1))
- Median fold increase of anti-gE antibody concentrations(At Month 2 and Month 13)
- Percentage of subjects with anti-gE antibody concentrations in terms of GMCs(At Day 1 (pre-vaccination) and Month 13)
- Number of subjects from the non-interventional pooled age group with seizures(Within 30 days after each vaccination (vaccines administered on day 1 and month 1))
- Vaccine Response Rate (VRR) for Anti-glycoprotein (Anti-gE) antibody concentrations(At Month 2 and Month 13)
- Occurrence of Herpes Zoster cases(From Visit Day 1 until Visit Month 13)
- Number of subjects from the non-interventional pooled age group with generalized convulsive seizures(Within 7 days after Visit Month 1)
- Number of subjects from the interventional pooled age group with seizures(Within 30 days after each vaccination (vaccines administered on day 1 and month 1))
- Number of subjects from the pooled age groups with any SAEs, pIMDs and biopsy confirmed renal allograft rejections(From Visit Day 1 until Visit Month 13)
- Number of subjects from the pooled age groups with HZ(From Visit Day 1 until Visit Month 13)
- Number of subjects from the interventional pooled age group with generalized convulsive seizures(Within 7 days after each vaccination (vaccines administered on day 1 and month 1))
- Percentage of subjects in the interventional pooled age group, with Anti-gE antibody concentrations in terms of GMCs(At Day 1, Month 2 and Month 13)