Trial Outcomes & Findings for Evaluation of Immune Memory to Twinrix or Comparator by Challenge Dose Administration 4 Years After Primary Vaccination (NCT NCT00684671)

NCT ID: NCT00684671

Last Updated: 2018-08-17

Results Overview

Anamnestic response was defined as: * for initially seronegative subjects, antibody concentration greater than or equal the cut-off \[≥ 15 Milli-International Units per Milliliter (mIU/mL)\], * for initially seropositive subjects with pre-vaccination antibody, concentration \< 100 mIU/mL: antibody concentration at least four times the pre-vaccination antibody concentration, * for initially seropositive subjects with pre-vaccination antibody concentration ≥ 100 mIU/mL: antibody concentration at least two times the pre-vaccination antibody concentration.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 506 participants
• Primary outcome timeframe: One month after the challenge dose.
• Results posted on: 2018-08-17

Participant Flow

Participant milestones

Measure	Twinrix Group Subjects received a single challenge dose of combined hepatitis A/hepatitis B vaccine (Twinrix).	Engerix + Havrix Group Subjects received separate administration of a single challenge dose of hepatitis B vaccine (Engerix) and hepatitis A vaccine (Havrix).	HB VAX PRO + Vaqta Group Subjects received separate administration of a single challenge dose of hepatitis B vaccine (HB VAX PRO) and hepatitis A vaccine (Vaqta).
Overall Study STARTED	172	170	164
Overall Study COMPLETED	169	170	164
Overall Study NOT COMPLETED	3	0	0

Reasons for withdrawal

Measure	Twinrix Group Subjects received a single challenge dose of combined hepatitis A/hepatitis B vaccine (Twinrix).	Engerix + Havrix Group Subjects received separate administration of a single challenge dose of hepatitis B vaccine (Engerix) and hepatitis A vaccine (Havrix).	HB VAX PRO + Vaqta Group Subjects received separate administration of a single challenge dose of hepatitis B vaccine (HB VAX PRO) and hepatitis A vaccine (Vaqta).
Overall Study Adverse Event	1	0	0
Overall Study Lost to Follow-up	1	0	0
Overall Study Alcoholic dependance	1	0	0

Baseline Characteristics

Evaluation of Immune Memory to Twinrix or Comparator by Challenge Dose Administration 4 Years After Primary Vaccination

Baseline characteristics by cohort

Measure	Twinrix Group n=172 Participants Subjects received a single challenge dose of combined hepatitis A/hepatitis B vaccine (Twinrix).	Engerix + Havrix Group n=170 Participants Subjects received separate administration of a single challenge dose of hepatitis B vaccine (Engerix) and hepatitis A vaccine (Havrix).	HB VAX PRO + Vaqta Group n=164 Participants Subjects received separate administration of a single challenge dose of hepatitis B vaccine (HB VAX PRO) and hepatitis A vaccine (Vaqta).	Total n=506 Participants Total of all reporting groups
Age, Continuous	58.4 years STANDARD_DEVIATION 8.70 • n=5 Participants	59.5 years STANDARD_DEVIATION 10.18 • n=7 Participants	59.1 years STANDARD_DEVIATION 9.16 • n=5 Participants	59.0 years STANDARD_DEVIATION 9.36 • n=4 Participants
Sex: Female, Male Female	85 Participants n=5 Participants	83 Participants n=7 Participants	85 Participants n=5 Participants	253 Participants n=4 Participants
Sex: Female, Male Male	87 Participants n=5 Participants	87 Participants n=7 Participants	79 Participants n=5 Participants	253 Participants n=4 Participants

PRIMARY outcome

Timeframe: One month after the challenge dose.

Population: Analysis was performed on the According-to-Protocol (ATP) cohort for analysis of immunogenicity.

Anamnestic response was defined as:

• for initially seronegative subjects, antibody concentration greater than or equal the cut-off [≥ 15 Milli-International Units per Milliliter (mIU/mL)],
• for initially seropositive subjects with pre-vaccination antibody, concentration < 100 mIU/mL: antibody concentration at least four times the pre-vaccination antibody concentration,
• for initially seropositive subjects with pre-vaccination antibody concentration ≥ 100 mIU/mL: antibody concentration at least two times the pre-vaccination antibody concentration.

Outcome measures

Measure	Twinrix Group n=167 Participants Subjects received a single challenge dose of combined hepatitis A/hepatitis B vaccine (Twinrix).	Engerix + Havrix Group n=168 Participants Subjects received separate administration of a single challenge dose of hepatitis B vaccine (Engerix) and hepatitis A vaccine (Havrix).	HB VAX PRO + Vaqta Group n=163 Participants Subjects received separate administration of a single challenge dose of hepatitis B vaccine (HB VAX PRO) and hepatitis A vaccine (Vaqta).
Number of Subjects With Anamnestic Response to the Challenge Dose for Anti-hepatitis A (Anti-HAV) Antibodies	164 Participants	164 Participants	162 Participants

PRIMARY outcome

Timeframe: One month after the challenge dose.

Population: Analysis was performed on the According-to-Protocol (ATP) cohort for analysis of immunogenicity.

Anamnestic response was defined as :

• for initially seronegative subjects, antibody concentration ≥ 10 Milli-International Units per Milliliter (mIU/mL),
• for initially seropositive subjects: antibody concentration at ≥ 4 fold the pre-vaccination antibody concentration.

Outcome measures

Measure	Twinrix Group n=167 Participants Subjects received a single challenge dose of combined hepatitis A/hepatitis B vaccine (Twinrix).	Engerix + Havrix Group n=168 Participants Subjects received separate administration of a single challenge dose of hepatitis B vaccine (Engerix) and hepatitis A vaccine (Havrix).	HB VAX PRO + Vaqta Group n=163 Participants Subjects received separate administration of a single challenge dose of hepatitis B vaccine (HB VAX PRO) and hepatitis A vaccine (Vaqta).
Number of Subjects With Anamnestic Response to the Challenge Dose for Anti-hepatitis B Surface Antigen (Anti-HBs) Antibodies	156 Participants	148 Participants	136 Participants

SECONDARY outcome

Timeframe: Prior to administration of challenge dose

Population: Analysis was performed on the Long-Term According-to-Protocol (LT ATP) cohort for analysis of immunogenicity.

Concentrations are given as geometric mean concentration (GMCs) expressed as mIU/mL.

Outcome measures

Measure	Twinrix Group n=167 Participants Subjects received a single challenge dose of combined hepatitis A/hepatitis B vaccine (Twinrix).	Engerix + Havrix Group n=168 Participants Subjects received separate administration of a single challenge dose of hepatitis B vaccine (Engerix) and hepatitis A vaccine (Havrix).	HB VAX PRO + Vaqta Group n=163 Participants Subjects received separate administration of a single challenge dose of hepatitis B vaccine (HB VAX PRO) and hepatitis A vaccine (Vaqta).
Anti-hepatitis A (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations anti-HAV	212.2 mIU/mL Interval 177.5 to 253.7	175.4 mIU/mL Interval 147.3 to 208.9	308.4 mIU/mL Interval 255.6 to 372.1
Anti-hepatitis A (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations anti-HBs	40.3 mIU/mL Interval 30.0 to 54.2	26.7 mIU/mL Interval 19.6 to 36.3	15.4 mIU/mL Interval 12.2 to 19.5

SECONDARY outcome

Timeframe: Two weeks and one month after the challenge dose

Population: Analysis was performed on the Log-Term According-to-Protocol (LT ATP) cohort for analysis of immunogenicity.

Concentrations are given as geometric mean concentration (GMCs) expressed as mIU/mL.

Outcome measures

Measure	Twinrix Group n=167 Participants Subjects received a single challenge dose of combined hepatitis A/hepatitis B vaccine (Twinrix).	Engerix + Havrix Group n=168 Participants Subjects received separate administration of a single challenge dose of hepatitis B vaccine (Engerix) and hepatitis A vaccine (Havrix).	HB VAX PRO + Vaqta Group n=163 Participants Subjects received separate administration of a single challenge dose of hepatitis B vaccine (HB VAX PRO) and hepatitis A vaccine (Vaqta).
Anti-hepatitis A (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Anti-HAV (at Day 14)	2255.0 mIU/mL Interval 2255.0 to 2636.8	1774.3 mIU/mL Interval 1493.5 to 2107.9	2712.9 mIU/mL Interval 2290.4 to 3213.3
Anti-hepatitis A (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Anti-HAV (at Day 30)	4062.0 mIU/mL Interval 3451.1 to 4781.0	3124.1 mIU/mL Interval 2630.4 to 3710.5	7481.6 mIU/mL Interval 6358.3 to 8803.3
Anti-hepatitis A (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Anti-HBs (at Day 14)	8936.9 mIU/mL Interval 6071.1 to 13155.4	1521.0 mIU/mL Interval 1012.5 to 2285.0	1222.4 mIU/mL Interval 821.3 to 1819.3
Anti-hepatitis A (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Anti-HBs (at Day 30)	7233.7 mIU/mL Interval 4868.2 to 10748.7	1242.5 mIU/mL Interval 823.5 to 1874.8	1075.1 mIU/mL Interval 717.2 to 1611.4

SECONDARY outcome

Timeframe: During the 4-day follow-up period after the challenge dose.

Solicited local symptoms assessed include pain, redness and swelling. Solicited general symptoms assessed include fatigue, gastrointestinal symptoms, headache and temperature (above 37 degree Celsius).

Outcome measures

Measure	Twinrix Group n=172 Participants Subjects received a single challenge dose of combined hepatitis A/hepatitis B vaccine (Twinrix).	Engerix + Havrix Group n=170 Participants Subjects received separate administration of a single challenge dose of hepatitis B vaccine (Engerix) and hepatitis A vaccine (Havrix).	HB VAX PRO + Vaqta Group n=164 Participants Subjects received separate administration of a single challenge dose of hepatitis B vaccine (HB VAX PRO) and hepatitis A vaccine (Vaqta).
Number of Subjects Reporting Solicited Symptoms Pain	42 Participants	35 Participants	46 Participants
Number of Subjects Reporting Solicited Symptoms Redness	22 Participants	10 Participants	19 Participants
Number of Subjects Reporting Solicited Symptoms Swelling	9 Participants	3 Participants	12 Participants
Number of Subjects Reporting Solicited Symptoms Fatigue	29 Participants	24 Participants	28 Participants
Number of Subjects Reporting Solicited Symptoms Gastrointestinal symptoms	5 Participants	8 Participants	5 Participants
Number of Subjects Reporting Solicited Symptoms Headache	21 Participants	20 Participants	18 Participants
Number of Subjects Reporting Solicited Symptoms Temperature	2 Participants	0 Participants	2 Participants

SECONDARY outcome

Timeframe: During the 31-day follow-up period after the challenge dose.

Unsolicited symptoms = any adverse event (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 was reported as an unsolicited adverse event.

Outcome measures

Measure	Twinrix Group n=172 Participants Subjects received a single challenge dose of combined hepatitis A/hepatitis B vaccine (Twinrix).	Engerix + Havrix Group n=170 Participants Subjects received separate administration of a single challenge dose of hepatitis B vaccine (Engerix) and hepatitis A vaccine (Havrix).	HB VAX PRO + Vaqta Group n=164 Participants Subjects received separate administration of a single challenge dose of hepatitis B vaccine (HB VAX PRO) and hepatitis A vaccine (Vaqta).
Number of Subjects Reporting Unsolicited Symptoms	28 Participants	10 Participants	21 Participants

SECONDARY outcome

Timeframe: Since the last study visit of the primary study long-term follow-up study up to challenge dose administration (1 year)

A serious adverse event (SAE) is any untoward medical occurrence that results in death, is life-threatening, requires hospitalisation or prolongation of existing hospitalisation, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or is a sign of suspected or confirmed hepatitis A or hepatitis B.

Outcome measures

Measure	Twinrix Group n=172 Participants Subjects received a single challenge dose of combined hepatitis A/hepatitis B vaccine (Twinrix).	Engerix + Havrix Group n=170 Participants Subjects received separate administration of a single challenge dose of hepatitis B vaccine (Engerix) and hepatitis A vaccine (Havrix).	HB VAX PRO + Vaqta Group n=164 Participants Subjects received separate administration of a single challenge dose of hepatitis B vaccine (HB VAX PRO) and hepatitis A vaccine (Vaqta).
Number of Subjects With Serious Adverse Events (SAEs) Since the Last Study Visit of the HAB-160 (NCT00603252) Long-term Follow-up Study Considered by the Investigator to Have a Causal Relationship to Primary Vaccination	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: During one month following the administration of the challenge dose

A serious adverse event (SAE) is any untoward medical occurrence that results in death, is life-threatening, requires hospitalisation or prolongation of existing hospitalisation, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or is a sign of suspected or confirmed hepatitis A or hepatitis B.

Outcome measures

Measure	Twinrix Group n=172 Participants Subjects received a single challenge dose of combined hepatitis A/hepatitis B vaccine (Twinrix).	Engerix + Havrix Group n=170 Participants Subjects received separate administration of a single challenge dose of hepatitis B vaccine (Engerix) and hepatitis A vaccine (Havrix).	HB VAX PRO + Vaqta Group n=164 Participants Subjects received separate administration of a single challenge dose of hepatitis B vaccine (HB VAX PRO) and hepatitis A vaccine (Vaqta).
Number of Subjects Reporting Serious Adverse Events (SAEs)	1 Participants	2 Participants	0 Participants

Adverse Events

Twinrix Group

Serious events: 1 serious events

Other events: 76 other events

Deaths: 0 deaths

Engerix + Havrix Group

Serious events: 2 serious events

Other events: 57 other events

Deaths: 0 deaths

HB VAX PRO + Vaqta Group

Serious events: 0 serious events

Other events: 75 other events

Deaths: 0 deaths

Serious adverse events

Measure	Twinrix Group n=172 participants at risk Subjects received a single challenge dose of combined hepatitis A/hepatitis B vaccine (Twinrix).	Engerix + Havrix Group n=170 participants at risk Subjects received separate administration of a single challenge dose of hepatitis B vaccine (Engerix) and hepatitis A vaccine (Havrix).	HB VAX PRO + Vaqta Group n=164 participants at risk Subjects received separate administration of a single challenge dose of hepatitis B vaccine (HB VAX PRO) and hepatitis A vaccine (Vaqta).
Vascular disorders Arterial occlusive disease	0.00% 0/172	0.59% 1/170	0.00% 0/164
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.00% 0/172	0.59% 1/170	0.00% 0/164
Renal and urinary disorders Nephritis interstitial	0.58% 1/172	0.00% 0/170	0.00% 0/164

Other adverse events

Measure	Twinrix Group n=172 participants at risk Subjects received a single challenge dose of combined hepatitis A/hepatitis B vaccine (Twinrix).	Engerix + Havrix Group n=170 participants at risk Subjects received separate administration of a single challenge dose of hepatitis B vaccine (Engerix) and hepatitis A vaccine (Havrix).	HB VAX PRO + Vaqta Group n=164 participants at risk Subjects received separate administration of a single challenge dose of hepatitis B vaccine (HB VAX PRO) and hepatitis A vaccine (Vaqta).
General disorders Pain	24.4% 42/172	20.6% 35/170	28.0% 46/164
General disorders Redness	12.8% 22/172	5.9% 10/170	11.6% 19/164
General disorders Swelling	5.2% 9/172	1.8% 3/170	7.3% 12/164
General disorders Fatigue	16.9% 29/172	14.1% 24/170	17.1% 28/164
General disorders Headache	12.2% 21/172	11.8% 20/170	11.0% 18/164

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

• Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
• Publication restrictions are in place

Restriction type: OTHER