A Global Phase 3 Safety Study of 120 mcg rLP2086 Vaccine in Adolescents and Young Adults Aged 10 to 25 Years

A Phase 3, Randomized, Active-controlled, Observer-blinded Trial To Assess The Safety And Tolerability Of A Meningococcal Serogroup B Bivalent Recombinant Lipoprotein (rlp2086) Vaccine Given In Healthy Subjects Aged Greater Than Or Equal To 10 To Less Than 26 Years

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01352793

Enrollment

5715

Registered

2011-05-12

Start date

2012-11-30

Completion date

2014-09-30

Last updated

2015-03-11

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Meningitis, Meningococcal

Keywords

phase 3 safety study, 5700 healthy subjects, 3 vaccine doses at month 0, 2, and 6, control HAV/saline/HAV

Brief summary

A multicenter phase 3 safety trial in which 5,700 subjects will be assigned in a 2:1 ratio to receive 120 μg rLP2086 vaccine in a 0, 2, 6 month schedule or control. The control group will receive HAVRIX vaccine at month 0 and 6 and saline at month 2. All subjects will be followed for 6 months after the last vaccination to assess safety and tolerability.

Interventions

BIOLOGICALrLP2086 vaccine

120 mcg, 3 doses, at month 0, 2, and 6.

BIOLOGICALcontrol

HAVRIX: 720 EL.U. or 1440 EL.Ul, 2 doses, at month 0 and 6. Placebo: normal saline injection, 1 dose, at month 2.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

PREVENTION

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

10 Years to 25 Years

Healthy volunteers

Yes

Inclusion criteria

* Healthy subjects aged 10 to 25 years.

Exclusion criteria

* Previous vaccination with Hepatitis A virus vaccine * Previous vaccination with investigational meningococcal B vaccine * History of culture-proven N. meningitidis serogroup B disease * Any neuroinflammatory or autoimmune condition * Any immune defect that would prevent an effective response to the study vaccine

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Participants With at Least One Serious Adverse Event (SAE) Throughout the Study	Vaccination 1 up to 6 months after Vaccination 3	An adverse event (AE) was any untoward medical occurrence in a participant who received study vaccine without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death, initial or prolonged inpatient hospitalization, life-threatening experience (immediate risk of dying), persistent or significant disability or incapacity, congenital anomaly.
Percentage of Participants With at Least One Medically Attended Adverse Event Within 30 Days After Vaccination 1	Within 30 days after Vaccination 1	A medically attended AE was defined as a non-serious AE that required medical attention.
Percentage of Participants With at Least One Medically Attended Adverse Event Within 30 Days After Vaccination 2	Within 30 days after Vaccination 2	A medically attended AE was defined as a non-serious AE that required medical attention.
Percentage of Participants With at Least One Medically Attended Adverse Event Within 30 Days After Vaccination 3	Within 30 days after Vaccination 3	A medically attended AE was defined as a non-serious AE that required medical attention.

Secondary

Measure	Time frame	Description
Percentage of Participants With at Least One Immediate Adverse Event (AE) After Each Study Vaccination	Within 30 minutes after Vaccination 1, 2, 3	An AE was any untoward medical occurrence in a participant who received study vaccine without regard to possibility of causal relationship. Any AE that occurred within the first 30 minutes after the administration of study vaccine (bivalent rLP2086, HAV vaccine or saline) was classified as an immediate AE. Here, 'N' signifies those participants who were evaluable for this measure during specified time period.
Percentage of Participants With at Least One Serious Adverse Event (SAE) During Pre-specified Time Periods	Within 30 days after Vaccination 1, 2, 3, any vaccination; vaccination phase (Vaccination 1 up to 1 month after Vaccination 3); follow-up phase (1 month up to 6 months after Vaccination 3)	An AE was any untoward medical occurrence in a participant who received study vaccine without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death, initial or prolonged inpatient hospitalization, life-threatening experience (immediate risk of dying), persistent or significant disability or incapacity, congenital anomaly. Here, 'N' signifies those participants who were evaluable for this measure during specified time period.
Number of Days Participant Missed School or Work Due to Adverse Events (AEs)	Vaccination 1 up to 1 month after Vaccination 3	—
Percentage of Participants With at Least One Medically Attended Adverse Event During Pre-specified Time Periods	Within 30 days after any vaccination; vaccination phase (Vaccination 1 up to 1 month after Vaccination 3); follow-up phase (1 month up to 6 months after Vaccination 3); throughout study (Vaccination 1 up to 6 months after Vaccination 3)	A medically attended AE was defined as a non-serious AE that required medical attention.
Percentage of Participants With at Least One Newly Diagnosed Chronic Medical Condition During Pre-specified Time Periods	Within 30 days after Vaccination 1, 2, 3, any vaccination; vaccination phase(Vaccination 1 up to 1 month after Vaccination 3); follow-up phase(1 month up to 6 months after Vaccination 3); throughout study(Vaccination 1 up to 6 months after Vaccination 3)	A newly diagnosed chronic medical condition was defined as a disease or medical condition that was not identified prior to study start and was expected to be persistent or otherwise long-lasting in its effects. Newly diagnosed chronic medical condition did not include illnesses considered to be temporary conditions. Here, 'N' signifies those participants who were evaluable for this measure during specified time period.
Percentage of Participants With at Least One Adverse Event (AE) During Pre-specified Time Periods	Within 30 days after Vaccination 1, 2, 3, any vaccination; vaccination phase (Vaccination 1 up to 1 month after Vaccination 3)	An AE was any untoward medical occurrence in a participant who received study vaccine without regard to possibility of causal relationship. Here, 'N' signifies those participants who were evaluable for this measure during specified time period.

Countries

Australia, Chile, Czechia, Denmark, Estonia, Finland, Germany, Lithuania, Poland, Spain, Sweden, United States

Participant flow

Pre-assignment details

A total of 5712 participants in 12 countries were enrolled in this study. Of these, 8 participants were randomized but did not receive study vaccination.

Participants by arm

Arm	Count
Group 1: rLP2086 Randomized to receive Neisseria meningitidis serogroup B (MnB) bivalent recombinant lipoprotein 2086 (rLP2086) vaccine on a 0, 2-, 6-month schedule	3,804
Group 2: HAV/Saline/HAV Randomized to receive hepatitis A virus (HAV) vaccine (Havrix) on a 0-, 6- month schedule and normal saline on 2-month	1,908
Total	5,712

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	44	10
Overall Study	Death	1	0
Overall Study	Lost to Follow-up	289	125
Overall Study	Medication error	2	2
Overall Study	No longer meets eligibility criteria	25	15
Overall Study	Other	25	7
Overall Study	Physician Decision	1	0
Overall Study	Pregnancy	26	8
Overall Study	Protocol Violation	44	23
Overall Study	Randomized but not vaccinated	8	0
Overall Study	Withdrawal by Subject	120	55

Baseline characteristics

Characteristic	Group 1: rLP2086	Group 2: HAV/Saline/HAV	Total
Age, Continuous	17.4 years STANDARD_DEVIATION 4.6	17.4 years STANDARD_DEVIATION 4.6	17.4 years STANDARD_DEVIATION 4.6
Sex: Female, Male Female	1962 Participants	994 Participants	2956 Participants
Sex: Female, Male Male	1842 Participants	914 Participants	2756 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	1,671 / 3,796	640 / 1,908
serious Total, serious adverse events	59 / 3,796	48 / 1,908

Outcome results

Primary

Percentage of Participants With at Least One Medically Attended Adverse Event Within 30 Days After Vaccination 1

A medically attended AE was defined as a non-serious AE that required medical attention.

Time frame: Within 30 days after Vaccination 1

Population: Vaccination 1 safety population included all participants who received the first dose of study vaccine (bivalent rLP2086 or HAV vaccine) and had safety information available from Vaccination 1 until prior to Vaccination 2.

Arm	Measure	Value (NUMBER)
Group 1: rLP2086	Percentage of Participants With at Least One Medically Attended Adverse Event Within 30 Days After Vaccination 1	7.03 percentage of participants
Group 2: HAV/Saline/HAV	Percentage of Participants With at Least One Medically Attended Adverse Event Within 30 Days After Vaccination 1	6.13 percentage of participants

Primary

Percentage of Participants With at Least One Medically Attended Adverse Event Within 30 Days After Vaccination 2

A medically attended AE was defined as a non-serious AE that required medical attention.

Time frame: Within 30 days after Vaccination 2

Population: Vaccination 2 safety population included all participants who received the second dose of study vaccine (bivalent rLP2086 or saline) and had safety information available from Vaccination 2 until prior to Vaccination 3.

Arm	Measure	Value (NUMBER)
Group 1: rLP2086	Percentage of Participants With at Least One Medically Attended Adverse Event Within 30 Days After Vaccination 2	5.50 percentage of participants
Group 2: HAV/Saline/HAV	Percentage of Participants With at Least One Medically Attended Adverse Event Within 30 Days After Vaccination 2	6.09 percentage of participants

Primary

Percentage of Participants With at Least One Medically Attended Adverse Event Within 30 Days After Vaccination 3

A medically attended AE was defined as a non-serious AE that required medical attention.

Time frame: Within 30 days after Vaccination 3

Population: Vaccination 3 safety population included all participants who received the third dose of study vaccine (bivalent rLP2086 or HAV vaccine or saline) and had safety information available from Vaccination 3 to post Vaccination 3 follow-up visit (1 month after Vaccination 3).

Arm	Measure	Value (NUMBER)
Group 1: rLP2086	Percentage of Participants With at Least One Medically Attended Adverse Event Within 30 Days After Vaccination 3	5.34 percentage of participants
Group 2: HAV/Saline/HAV	Percentage of Participants With at Least One Medically Attended Adverse Event Within 30 Days After Vaccination 3	5.50 percentage of participants

Primary

Percentage of Participants With at Least One Serious Adverse Event (SAE) Throughout the Study

An adverse event (AE) was any untoward medical occurrence in a participant who received study vaccine without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death, initial or prolonged inpatient hospitalization, life-threatening experience (immediate risk of dying), persistent or significant disability or incapacity, congenital anomaly.

Time frame: Vaccination 1 up to 6 months after Vaccination 3

Population: Safety population included all participants who received at least 1 dose of study vaccine (bivalent rLP2086 or HAV vaccine or saline) and had safety information available.

Arm	Measure	Value (NUMBER)
Group 1: rLP2086	Percentage of Participants With at Least One Serious Adverse Event (SAE) Throughout the Study	1.55 percentage of participants
Group 2: HAV/Saline/HAV	Percentage of Participants With at Least One Serious Adverse Event (SAE) Throughout the Study	2.52 percentage of participants

Secondary