Download PDF

Clinical Trial Results:
A Phase 3 Double-Blind Randomized Controlled Trial to Compare the Immunogenicity and Safety of a Three-dose Regimen of Sci-B-Vac™ to a Three-dose Regimen of Engerix-B® in Adults (PROTECT)

Summary
EudraCT number	2017-001819-36
Trial protocol	FI BE
Global end of trial date	08 Apr 2019

Results information
Results version number	v1(current)
This version publication date	08 Jan 2023
First version publication date	08 Jan 2023
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

Sci-B-Vac–001

ISRCTN number

US NCT number

NCT03393754

WHO universal trial number (UTN)

Sponsor organisation name

VBI Vaccines

Sponsor organisation address

310 Hunt Club East, Nepean, Canada, K1V 1C1

Public contact

Bebi Yassin-Rajkumar, VBI Vaccines Inc., +1 613749-4200 151, byassin-rajkumar@vbivaccines.com

Scientific contact

Dr Francisco Diaz-Mitoma, VBI Vaccines Inc., +1 613749-4200 151, fdiazmitoma@vbivaccines.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

17 Jul 2020

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

08 Apr 2019

Was the trial ended prematurely?

Main objective of the trial

Co-Primary Objectives of the Trial were: To demonstrate that the seroprotection rate (SPR) 4 weeks after completion of the three-dose regimen of Sci-B-Vac™ is non-inferior to the SPR 4 weeks after completion of the three-dose regimen of Engerix-B® in adults ≥18 years of old i.e. the lower bound of the 95% two-sided confidence interval (CI) of the difference between the SPR in the Sci-B-Vac™ arm minus the SPR in the Engerix-B® arm, achieved 4 weeks after receiving the third vaccination, will be > - 5%. and To demonstrate that the SPR 4 weeks after completion of the three-dose regimen of Sci-B-Vac™ is superior to the SPR 4 weeks after completion of the three-dose regimen of Engerix-B® in older adults ≥ 45 years old i.e. the lower bound of the 95% two-sided CI of the difference between the SPR in the Sci-B-Vac™ arm minus the SPR in the Engerix-B® arm, achieved 4 weeks after receiving the third vaccination, will be > 5%.

Protection of trial subjects

An independent Data Monitoring Committee (DMC) was established to monitor subject safety. Subjects were provided with a 28-day diary card to record vaccine reactions. Subjects recorded solicited local and systemic AEs on the day of vaccination and for the next 6 days. A safety follow-up telephone call was made 7 days after each vaccination to inquire about local and systemic reactions. Subjects were followed a minimum of 48 weeks after receiving the first vaccination at Study Day 0, with at least a 24 week follow-up safety assessments after receiving the third vaccination.

Background therapy

Evidence for comparator

Engerix-B is approved for active immunization against hepatitis B virus infection (HBV) caused by all known subtypes in non immune subjects.

Actual start date of recruitment

24 Nov 2017

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Canada: 259

Country: Number of subjects enrolled

United States: 680

Country: Number of subjects enrolled

Belgium: 63

Country: Number of subjects enrolled

Finland: 605

Worldwide total number of subjects

1607

EEA total number of subjects

668

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

1015

From 65 to 84 years

589

85 years and over

Subject disposition

Top of page

Recruitment details

Participants were recruited through radio and newspaper advertisements.

Screening details

Screening was conducted within 28 days (4 weeks) prior to the first vaccination.

Period 1 title

Overall Trial (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Assessor

Blinding implementation details

This was a double-blind study. Both subjects and the study center staff performing outcome measurement were blinded. Randomization and administration of study vaccine was by unblinded qualified health personnel not involved in assessment of outcome measures, whose sole role was to prepare and administer the allocated study vaccine and to perform activities requiring vial handling.

Are arms mutually exclusive

Yes

Sci-B-Vac®

Arm description

Sci-B-Vac® (hepatitis B vaccine) Hepatitis B Vaccination, Solution, 10ug, IM injection at Days 0, 28, and 168. Hepatitis B Vaccination: Prophylactic Hepatitis B Vaccination

Arm type

Experimental

Investigational medicinal product name

Sci-B-Vac®

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

The vaccination schedule consists of 3 doses (1 mL each) given according to the following schedule: first dose at an elected date; second dose 1 month after the first dose; third dose 6 months after the first dose. Injected intramuscularly (IM) into the deltoid region.

Engerix-B®

Arm description

Engerix-B® (hepatitis B vaccine) Hepatitis B Vaccination, Solution, 20ug, IM injection at Days 0, 28, and 168. Hepatitis B Vaccination: Prophylactic Hepatitis B Vaccination

Arm type

Active comparator

Investigational medicinal product name

Engerix-B®

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Number of subjects in period 1	Sci-B-Vac®	Engerix-B®
Started	796	811
Completed	758	785
Not completed	38	26
Adverse event, non-fatal	5	5
Other	30	21
Pregnancy	3	-

Baseline characteristics

Top of page

Reporting group title

Sci-B-Vac®

Reporting group description

Sci-B-Vac® (hepatitis B vaccine) Hepatitis B Vaccination, Solution, 10ug, IM injection at Days 0, 28, and 168. Hepatitis B Vaccination: Prophylactic Hepatitis B Vaccination

Reporting group title

Engerix-B®

Reporting group description

Engerix-B® (hepatitis B vaccine) Hepatitis B Vaccination, Solution, 20ug, IM injection at Days 0, 28, and 168. Hepatitis B Vaccination: Prophylactic Hepatitis B Vaccination

Reporting group values	Sci-B-Vac®	Engerix-B®	Total
Number of subjects	796	811	1607
Age categorical
Units: Subjects
Age continuous
Units: years
arithmetic mean (full range (min-max))	56.6 (18 to 86)	56.6 (18 to 90)	-
Gender categorical
Units: Subjects
Female	481	508	989
Male	315	303	618

Subject analysis set title

Safety Set

Subject analysis set type

Safety analysis

Subject analysis set description

All subjects in the All Enrolled Set who received at least 1 vaccination. Subjects were analyzed as vaccinated, ie, a subject was assigned according to the vaccination received. In case of vaccination error, subjects were analyzed as treated.

Subject analysis set title

Full Analysis Set (FAS)

Subject analysis set type

Full analysis

Subject analysis set description

subjects who received at least 1 injection and had at least baseline and 1 post baseline immunogenicity assessment.

Subject analysis set title

Per Protocol Set (PPS)

Subject analysis set type

Per protocol

Subject analysis set description

All subjects in the full analysis set who received all 3 injections, had at least baseline and 1 post-baseline immunogenicity assessment (at the time point of interest), were seronegative at baseline, and had no major protocol deviations leading to exclusion.

Subject analysis sets values	Safety Set	Full Analysis Set (FAS)	Per Protocol Set (PPS)
Number of subjects	1607	1585	1447
Age categorical
Units: Subjects
Age continuous
Units: years
arithmetic mean (full range (min-max))	56.6 (18 to 90)	56.6 (18 to 90)	56.8 (18 to 90)
Gender categorical
Units: Subjects
Female	989	975	894
Male	618	610	553

End points

Top of page

Reporting group title

Sci-B-Vac®

Reporting group description

Sci-B-Vac® (hepatitis B vaccine) Hepatitis B Vaccination, Solution, 10ug, IM injection at Days 0, 28, and 168. Hepatitis B Vaccination: Prophylactic Hepatitis B Vaccination

Reporting group title

Engerix-B®

Reporting group description

Engerix-B® (hepatitis B vaccine) Hepatitis B Vaccination, Solution, 20ug, IM injection at Days 0, 28, and 168. Hepatitis B Vaccination: Prophylactic Hepatitis B Vaccination

Subject analysis set title

Safety Set

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

Full Analysis Set (FAS)

Subject analysis set type

Full analysis

Subject analysis set description

subjects who received at least 1 injection and had at least baseline and 1 post baseline immunogenicity assessment.

Subject analysis set title

Per Protocol Set (PPS)

Subject analysis set type

Per protocol

Subject analysis set description

Primary: Seroprotection rate (SPR) defined as percentage of adults ≥ 18 years old achieving anti-HBs levels of ≥10 mIU/mL in serum at study day 196

Top of page

End point title

Seroprotection rate (SPR) defined as percentage of adults ≥ 18 years old achieving anti-HBs levels of ≥10 mIU/mL in serum at study day 196

End point description

To demonstrate that the SPR 4 weeks after completion of the three-dose regimen of Sci-B-Vac® is non-inferior to a three-dose regimen of Engerix-B® in adults ≥18 years old; i.e. the lower bound of the 95% two-sided confidence interval (CI) of the difference between the SPR in the Sci-B-Vac® arm minus the SPR in the Engerix-B® arm, achieved 4 weeks after the third vaccination, will be > - 5%.

End point type

Primary

End point timeframe

Day 196

End point values	Sci-B-Vac®	Engerix-B®
Number of subjects analysed	718	723
Units: Percentage of Subjects
number (confidence interval 95%)	91.36 (89.07 to 93.32)	76.49 (73.22 to 79.53)

Co-Primary1

Statistical analysis description

Seroprotection rate (SPR) at Study Day 196 in adults >= 18 years of age using PPS

Comparison groups

Sci-B-Vac® v Engerix-B®

Number of subjects included in analysis

1441

Analysis specification

Pre-specified

Analysis type

non-inferiority

Method

Miettinen and Nurminen

Parameter type

Difference in proportions

Point estimate

14.88

Confidence interval

level

95%

sides

2-sided

lower limit

11.18

upper limit

18.63

Primary: Seroprotection rate (SPR) defined as percentage of adults ≥ 45 years old achieving anti-HBs levels of ≥10 mIU/mL in serum at study day 196

Top of page

End point title

Seroprotection rate (SPR) defined as percentage of adults ≥ 45 years old achieving anti-HBs levels of ≥10 mIU/mL in serum at study day 196

End point description

To demonstrate that the SPR 4 weeks after completion of the three-dose regimen of Sci-B-Vac® is superior to the SPR 4 weeks after completion of the three-dose regimen of Engerix-B® in older adults ≥ 45 years old i.e. the lower bound of the 95% two-sided CI of the difference between the SPR in the Sci-B-Vac® arm minus the SPR in the Engerix-B® arm, achieved 4 weeks after receiving the third vaccination, will be > 5%.

End point type

Primary

End point timeframe

Day 196

End point values	Sci-B-Vac®	Engerix-B®
Number of subjects analysed	625	627
Units: Percentage of Subjects
number (confidence interval 95%)	89.44 (86.76 to 91.74)	73.05 (69.39 to 76.48)

Co-Primary2

Statistical analysis description

Seroprotection rate (SPR) at Study Day 196 in adults >= 45 years of age using FAS

Comparison groups

Sci-B-Vac® v Engerix-B®

Number of subjects included in analysis

1252

Analysis specification

Pre-specified

Analysis type

superiority

Method

Miettinen and Nurminen

Parameter type

Difference in proportions

Point estimate

16.39

Confidence interval

level

95%

sides

2-sided

lower limit

12.17

upper limit

20.65

Secondary: Seroprotection rate (SPR) of Sci-B-Vac at study day 168 compared with Engerix-B at study day 196 in adults >= 18 years of age

Top of page

End point title

Seroprotection rate (SPR) of Sci-B-Vac at study day 168 compared with Engerix-B at study day 196 in adults >= 18 years of age

End point description

To determine whether the SPR after receiving 2 vaccinations of Sci-B-Vac™, evaluated at 4 weeks and 20 weeks after receiving the second vaccination (just prior to receiving the third vaccination), is non-inferior to the SPR 4 weeks after receiving the third vaccination with Engerix-B®

End point type

Secondary

End point timeframe

Sci-B-Vac at Study Day 168 compared with Engerix-B at Study Day 196

End point values	Sci-B-Vac®	Engerix-B®
Number of subjects analysed	717	723
Units: Percentage of Subjects
number (confidence interval 95%)	65.97 (62.37 to 69.44)	76.49 (73.22 to 79.53)

Secondary1

Statistical analysis description

Seroprotection rate (SPR) of Sci-B-Vac at Study Day 168 compared with Engerix-B at Day 196 in adults >= 18 years of age

Comparison groups

Sci-B-Vac® v Engerix-B®

Number of subjects included in analysis

1440

Analysis specification

Pre-specified

Analysis type

non-inferiority

Method

Miettinen and Nurminen

Parameter type

Difference in proportions

Point estimate

-10.52

Confidence interval

level

95%

sides

2-sided

lower limit

-15.15

upper limit

-5.86

Secondary: Number of subjects reporting solicited local adverse events day 1 through day 7 after any vaccination

Top of page

End point title

Number of subjects reporting solicited local adverse events day 1 through day 7 after any vaccination

End point description

Analysis of local solicited adverse events with an interval of onset of Day 1 to Day 7 after any vaccination with either Sci-B-Vac® or Engerix-B®, in adults ≥18 years old.

End point type

Secondary

End point timeframe

Day of vaccination and 6 subsequent days

End point values	Sci-B-Vac®	Engerix-B®
Number of subjects analysed	796	811
Units: number of events	572	379

No statistical analyses for this end point

Secondary: Number of subjects reporting solicited systemic adverse events day 1 through day 7 after any vaccination

Top of page

End point title

Number of subjects reporting solicited systemic adverse events day 1 through day 7 after any vaccination

End point description

Analysis of systemic solicited adverse events with an interval of onset of Day 1 to Day 7 after any vaccination with either Sci-B-Vac® or Engerix-B®, in adults ≥18 years old.

End point type

Secondary

End point timeframe

Day of vaccine administration and six subsequent days

End point values	Sci-B-Vac®	Engerix-B®
Number of subjects analysed	796	811
Units: Number of events	445	396

No statistical analyses for this end point

Secondary: Number of subjects reporting unsolicited adverse events through end of study

Top of page

End point title

Number of subjects reporting unsolicited adverse events through end of study

End point description

Summary of unsolicited treatment-emergent adverse events reported in ≥1% of subjects after vaccination with either Sci-B-Vac® or Engerix-B®, in adults ≥18 years old.

End point type

Secondary

End point timeframe

Through end of study (day 336)

End point values	Sci-B-Vac®	Engerix-B®
Number of subjects analysed	796	811
Units: Number of events	418	441

No statistical analyses for this end point

Secondary: Number of subjects reporting serious adverse events through end of study

Top of page

End point title

Number of subjects reporting serious adverse events through end of study

End point description

Summary of unsolicited serious adverse events reported after vaccination with either Sci-B-Vac® or Engerix-B®, in adults ≥18 years old.

End point type

Secondary

End point timeframe

Through end of study (day 336)

End point values	Sci-B-Vac®	Engerix-B®
Number of subjects analysed	796	811
Units: Number of events	35	27

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

48-week follow-up for serious adverse events (SAEs), medically significant events or new onset of chronic illness (NOCI) (at least 24 weeks after receiving the third vaccination)

Adverse event reporting additional description

Safety evaluations included standardized methods for local and systemic vaccine reactions, repeated vital signs and physical examinations, medically significant events or new onset of chronic illness (NOCI), and changes in concomitant medications

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

20.1

Reporting group title

Sci-B-Vac®

Reporting group description

Sci-B-Vac® (hepatitis B vaccine) Hepatitis B Vaccination, Solution, 10ug, IM injection at Days 0, 28, and 168. Hepatitis B Vaccination: Prophylactic Hepatitis B Vaccination

Reporting group title

Engerix-B®

Reporting group description

Engerix-B® (hepatitis B vaccine) Hepatitis B Vaccination, Solution, 20ug, IM injection at Days 0, 28, and 168. Hepatitis B Vaccination: Prophylactic Hepatitis B Vaccination

Serious adverse events	Sci-B-Vac®	Engerix-B®
Total subjects affected by serious adverse events
subjects affected / exposed	32 / 796 (4.02%)	21 / 811 (2.59%)
number of deaths (all causes)	0	0
number of deaths resulting from adverse events	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer
subjects affected / exposed	0 / 796 (0.00%)	2 / 811 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Breast cancer
subjects affected / exposed	0 / 796 (0.00%)	1 / 811 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Endometrial cancer stage II
subjects affected / exposed	1 / 796 (0.13%)	0 / 811 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Invasive ductal breast carcinoma
subjects affected / exposed	1 / 796 (0.13%)	0 / 811 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Lung adenocarcinoma
subjects affected / exposed	1 / 796 (0.13%)	0 / 811 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Malignant melanoma
subjects affected / exposed	0 / 796 (0.00%)	1 / 811 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Prostate cancer
subjects affected / exposed	0 / 796 (0.00%)	1 / 811 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Transitional cell carcinoma
subjects affected / exposed	1 / 796 (0.13%)	0 / 811 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Vascular disorders
Aortic stenosis
subjects affected / exposed	0 / 796 (0.00%)	1 / 811 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pregnancy, puerperium and perinatal conditions
Subchorionic haemorrhage
subjects affected / exposed	1 / 796 (0.13%)	0 / 811 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
General disorders and administration site conditions
Chest pain
subjects affected / exposed	0 / 796 (0.00%)	1 / 811 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Asthma
subjects affected / exposed	0 / 796 (0.00%)	1 / 811 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Investigations
Troponin increased
subjects affected / exposed	0 / 796 (0.00%)	1 / 811 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Injury, poisoning and procedural complications
Ankle fracture
subjects affected / exposed	1 / 796 (0.13%)	1 / 811 (0.12%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Back injury
subjects affected / exposed	0 / 796 (0.00%)	1 / 811 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Head injury
subjects affected / exposed	0 / 796 (0.00%)	1 / 811 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Joint dislocation
subjects affected / exposed	1 / 796 (0.13%)	0 / 811 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Tendon rupture
subjects affected / exposed	1 / 796 (0.13%)	0 / 811 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Ulna fracture
subjects affected / exposed	1 / 796 (0.13%)	0 / 811 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Congenital, familial and genetic disorders
Trisomy 21
subjects affected / exposed	1 / 796 (0.13%)	0 / 811 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac disorders
Atrial fibrillation
subjects affected / exposed	1 / 796 (0.13%)	2 / 811 (0.25%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac failure congestive
subjects affected / exposed	2 / 796 (0.25%)	0 / 811 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Angina pectoris
subjects affected / exposed	1 / 796 (0.13%)	0 / 811 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Atrioventricular block second degree
subjects affected / exposed	0 / 796 (0.00%)	1 / 811 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Myocardial infarction
subjects affected / exposed	1 / 796 (0.13%)	0 / 811 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Nodal arrhythmia
subjects affected / exposed	1 / 796 (0.13%)	0 / 811 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Nervous system disorders
Cerebrovascular accident
subjects affected / exposed	1 / 796 (0.13%)	1 / 811 (0.12%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cerebral infarction
subjects affected / exposed	1 / 796 (0.13%)	0 / 811 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Peroneal nerve palsy
subjects affected / exposed	1 / 796 (0.13%)	0 / 811 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Syncope
subjects affected / exposed	1 / 796 (0.13%)	0 / 811 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Ear and labyrinth disorders
Vertigo
subjects affected / exposed	1 / 796 (0.13%)	0 / 811 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal disorders
Colitis ischaemic
subjects affected / exposed	0 / 796 (0.00%)	1 / 811 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Diaphragmatic hernia
subjects affected / exposed	0 / 796 (0.00%)	1 / 811 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal haemorrhage
subjects affected / exposed	0 / 796 (0.00%)	1 / 811 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Intra-abdominal haematoma
subjects affected / exposed	1 / 796 (0.13%)	0 / 811 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Obstructive pancreatitis
subjects affected / exposed	1 / 796 (0.13%)	0 / 811 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatobiliary disorders
Cholelithiasis
subjects affected / exposed	1 / 796 (0.13%)	1 / 811 (0.12%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Angioedema
subjects affected / exposed	1 / 796 (0.13%)	0 / 811 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Renal and urinary disorders
Nephrolithiasis
subjects affected / exposed	0 / 796 (0.00%)	1 / 811 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Osteoarthritis
subjects affected / exposed	1 / 796 (0.13%)	1 / 811 (0.12%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Back pain
subjects affected / exposed	1 / 796 (0.13%)	0 / 811 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Infections and infestations
Appendicitis
subjects affected / exposed	1 / 796 (0.13%)	0 / 811 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Escherichia sepsis
subjects affected / exposed	1 / 796 (0.13%)	0 / 811 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gastroenteritis viral
subjects affected / exposed	1 / 796 (0.13%)	0 / 811 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal infection
subjects affected / exposed	0 / 796 (0.00%)	1 / 811 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Influenza
subjects affected / exposed	1 / 796 (0.13%)	0 / 811 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	1 / 796 (0.13%)	0 / 811 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pyelonephritis acute
subjects affected / exposed	0 / 796 (0.00%)	1 / 811 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Sepsis
subjects affected / exposed	1 / 796 (0.13%)	0 / 811 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Subcutaneous abscess
subjects affected / exposed	1 / 796 (0.13%)	0 / 811 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	0 / 796 (0.00%)	1 / 811 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Urosepsis
subjects affected / exposed	1 / 796 (0.13%)	0 / 811 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Sci-B-Vac®	Engerix-B®
Total subjects affected by non serious adverse events
subjects affected / exposed	625 / 796 (78.52%)	526 / 811 (64.86%)
Nervous system disorders
Headache
Additional description: Headache events that occurred after 7 days post-vaccination were considered as unsolicited AE
subjects affected / exposed	274 / 796 (34.42%)	253 / 811 (31.20%)
occurrences all number	431	377
General disorders and administration site conditions
Fatigue
Additional description: Fatigue events that occurred after 7 days post-vaccination were considered as unsolicited AE
subjects affected / exposed	242 / 796 (30.40%)	250 / 811 (30.83%)
occurrences all number	377	387
Injection site pain
Additional description: Injection site pain events that occurred after 7 days post-vaccination were considered as unsolicited AE
subjects affected / exposed	564 / 796 (70.85%)	364 / 811 (44.88%)
occurrences all number	1194	619
Injection site pruritus
Additional description: Injection site pruritus events that occurred after 7 days post-vaccination were considered as unsolicited AE
subjects affected / exposed	76 / 796 (9.55%)	66 / 811 (8.14%)
occurrences all number	99	84
Gastrointestinal disorders
Diarrhoea
Additional description: Diarrhoea events that occurred after 7 days post-vaccination were considered as unsolicited AE
subjects affected / exposed	85 / 796 (10.68%)	104 / 811 (12.82%)
occurrences all number	111	129
Nausea
Additional description: Nausea events that occurred after 7 days post-vaccination were considered as unsolicited AE
subjects affected / exposed	57 / 796 (7.16%)	77 / 811 (9.49%)
occurrences all number	74	94
Musculoskeletal and connective tissue disorders
Myalgia
Additional description: Myalgia events that occurred after 7 days post-vaccination were considered as unsolicited AE
subjects affected / exposed	283 / 796 (35.55%)	205 / 811 (25.28%)
occurrences all number	432	286
Infections and infestations
Upper respiratory tract infection
subjects affected / exposed	50 / 796 (6.28%)	52 / 811 (6.41%)
occurrences all number	56	57

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

17 Jul 2017

The overall reason for the amendment is to change the short-term clinical laboratory follow-up on the entire study population to a more intensive clinical laboratory follow up over the full three-dose regimen on a subset (at least 10%) of the entire study population, and to provide per-protocol clarifications in response to study center inquiries.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Clinical trials

Clinical Trial Results:
A Phase 3 Double-Blind Randomized Controlled Trial to Compare the Immunogenicity and Safety of a Three-dose Regimen of Sci-B-Vac™ to a Three-dose Regimen of Engerix-B® in Adults (PROTECT)

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Seroprotection rate (SPR) defined as percentage of adults ≥ 18 years old achieving anti-HBs levels of ≥10 mIU/mL in serum at study day 196

Primary: Seroprotection rate (SPR) defined as percentage of adults ≥ 18 years old achieving anti-HBs levels of ≥10 mIU/mL in serum at study day 196

Primary: Seroprotection rate (SPR) defined as percentage of adults ≥ 45 years old achieving anti-HBs levels of ≥10 mIU/mL in serum at study day 196

Primary: Seroprotection rate (SPR) defined as percentage of adults ≥ 45 years old achieving anti-HBs levels of ≥10 mIU/mL in serum at study day 196

Secondary: Seroprotection rate (SPR) of Sci-B-Vac at study day 168 compared with Engerix-B at study day 196 in adults >= 18 years of age

Secondary: Seroprotection rate (SPR) of Sci-B-Vac at study day 168 compared with Engerix-B at study day 196 in adults >= 18 years of age

Secondary: Number of subjects reporting solicited local adverse events day 1 through day 7 after any vaccination

Secondary: Number of subjects reporting solicited local adverse events day 1 through day 7 after any vaccination

Secondary: Number of subjects reporting solicited systemic adverse events day 1 through day 7 after any vaccination

Secondary: Number of subjects reporting solicited systemic adverse events day 1 through day 7 after any vaccination

Secondary: Number of subjects reporting unsolicited adverse events through end of study

Secondary: Number of subjects reporting unsolicited adverse events through end of study

Secondary: Number of subjects reporting serious adverse events through end of study

Secondary: Number of subjects reporting serious adverse events through end of study

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

Clinical Trial Results: A Phase 3 Double-Blind Randomized Controlled Trial to Compare the Immunogenicity and Safety of a Three-dose Regimen of Sci-B-Vac™ to a Three-dose Regimen of Engerix-B® in Adults (PROTECT)

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Seroprotection rate (SPR) defined as percentage of adults ≥ 18 years old achieving anti-HBs levels of ≥10 mIU/mL in serum at study day 196

Primary: Seroprotection rate (SPR) defined as percentage of adults ≥ 18 years old achieving anti-HBs levels of ≥10 mIU/mL in serum at study day 196

Primary: Seroprotection rate (SPR) defined as percentage of adults ≥ 45 years old achieving anti-HBs levels of ≥10 mIU/mL in serum at study day 196

Primary: Seroprotection rate (SPR) defined as percentage of adults ≥ 45 years old achieving anti-HBs levels of ≥10 mIU/mL in serum at study day 196

Secondary: Seroprotection rate (SPR) of Sci-B-Vac at study day 168 compared with Engerix-B at study day 196 in adults >= 18 years of age

Secondary: Seroprotection rate (SPR) of Sci-B-Vac at study day 168 compared with Engerix-B at study day 196 in adults >= 18 years of age

Secondary: Number of subjects reporting solicited local adverse events day 1 through day 7 after any vaccination

Secondary: Number of subjects reporting solicited local adverse events day 1 through day 7 after any vaccination

Secondary: Number of subjects reporting solicited systemic adverse events day 1 through day 7 after any vaccination

Secondary: Number of subjects reporting solicited systemic adverse events day 1 through day 7 after any vaccination

Secondary: Number of subjects reporting unsolicited adverse events through end of study

Secondary: Number of subjects reporting unsolicited adverse events through end of study

Secondary: Number of subjects reporting serious adverse events through end of study

Secondary: Number of subjects reporting serious adverse events through end of study

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Phase 3 Double-Blind Randomized Controlled Trial to Compare the Immunogenicity and Safety of a Three-dose Regimen of Sci-B-Vac™ to a Three-dose Regimen of Engerix-B® in Adults (PROTECT)