Clinical trial NCT05561673: A Study on the Safety and Immune Response of AS37 Together With Hepatitis B Antigen in Adults Aged 18-45 Years
Official title: A Phase I/IIa, Open-label, Randomised, Controlled, Multi-country, Dose-escalation Study to Assess the Safety and Immunogenicity of AS37 in Combination With the Hepatitis B Surface Antigen (HBsAg), According to a 0-1 Month Schedule, in Healthy, HBs naïve, Adults Aged 18-45 Years
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Hepatitis B
Keywords: Hepatitis B
Hepatitis B virus
Hepatitis B surface antigen
Aluminum hydroxide
Adjuvant System
Safety
Immunogenicity
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2022-09-30
Enrollment: 122
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This study is conducted to assess safety and immunogenicity of GSK's HBsAg vaccine adjuvanted with GSK's AS37 adjuvant system in healthy, HBs naïve, adults aged 18-45 years and to differentiate GSK's AS37 adjuvant system from other approved adjuvant systems and from an aluminum-based adjuvant.


Eligibility criteria: Inclusion Criteria:

* Participants who the investigator believe can and will comply with the requirements of the protocol.
* Written informed consent obtained from the participant prior to performance of any study-specific procedure.
* Healthy participants as established by medical history, clinical examination and clinical laboratory assessment before entering the study.
* A male or female between, and including, 18 and 45 years at the time of the first study intervention administration.
* Female participants of non-childbearing potential may be enrolled in the study. Non-childbearing potential is defined as pre-menarche, current bilateral tubal ligation or occlusion, hysterectomy, bilateral ovariectomy or post-menopause.
* Female participants of childbearing potential may be enrolled in the study, if the participant:

  * has practiced adequate contraception for 1 month prior to study intervention administration, and
  * has a negative pregnancy test on the day of study intervention administration, and
  * has agreed to continue adequate contraception during the entire treatment period and for at least 3 months after completion of the study intervention administration series.
  * blood sample for simultaneous follicle-stimulating hormone (FSH) and estradiol levels may be collected at the discretion of the investigator to confirm non-reproductive potential according to local laboratory reference range.

Exclusion Criteria:

Medical conditions

* Previous vaccination against Hepatitis B.
* Positive for anti-HBs antibodies or anti-HBc antibodies or HBsAg.
* Any previous administration of monophosphoryl lipid (MPL) and/or AS37.
* Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
* Any confirmed or suspected autoimmune disease.
* History of any reaction or hypersensitivity likely to be exacerbated by any component of the study intervention(s).
* Recurrent history or uncontrolled neurological disorders or seizures.
* Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the participant due to participation in the study.
* Any clinically significant\* haematological and/or biochemical laboratory abnormality.

  \*The investigator should use his/her clinical judgement to decide which abnormalities are clinically significant.
* Any past or current malignancies and lymphoproliferative disorders.

Prior/Concomitant therapy

* Use of any investigational or non-registered product (drug or vaccine) other than the study intervention(s) during the period beginning 30 days before the first dose of study intervention(s) or their planned use during the study period.
* Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting 30 days before each dose and ending 30 days after each dose of study intervention(s) administration with the exception of influenza vaccine (pandemic or seasonal).
* A vaccine not foreseen by the study protocol administered during the period starting at Visit 1 or 30 days before each dose and ending 30 days after the last dose of study intervention(s) administration\*, with the exception of influenza vaccine (pandemic or seasonal).

  \*In case emergency mass vaccination for an unforeseen public health threat (e.g. a pandemic) is organised by public health authorities outside the routine immunisation programme, the time period described above can be reduced if necessary for that vaccine, provided it is licensed/authorised and used according to its Product Information.
* Administration of long-acting immune-modifying drugs at any time during the study period.
* Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs during the period starting 3 months before the first study intervention dose(s). For corticosteroids, this will mean prednisone equivalent ≥ 20 mg/day. Inhaled and topical steroids are allowed.
* Administration of immunoglobulins and/or any blood products or plasma derivatives during the period starting 3 months before the administration of the first dose of study intervention(s) or planned administration during the study period.

Prior/Concurrent clinical study experience

* Concurrently participating in another clinical study, at any time during the study period, in which the participant has been or will be exposed to an investigational intervention.

Other exclusions

* Pregnant or lactating female.
* Female planning to become pregnant or planning to discontinue contraceptive precautions.
* History of chronic alcohol consumption and/or drug abuse.
* Any study personnel or their immediate depandants, family, or household members.

Specific exclusion for MRI-assessable subgroup participants (post-randomization procedure)

* Presence of pacemakers, metal implants and/or prostheses.
* Claustrophobia.

Primary outcomes:
measure: Percentage of participants with solicited administration site events
timeFrame: Within 14 days after Dose 1 administration (Dose 1 administered at Day 1)
measure: Percentage of participants with solicited administration site events
timeFrame: Within 14 days after Dose 2 administration (Dose 2 administered at Day 31)
measure: Percentage of participants with solicited systemic events
timeFrame: Within 14 days after Dose 1 administration (Dose 1 administered at Day 1)
measure: Percentage of participants with solicited systemic events
timeFrame: Within 14 days after Dose 2 administration (Dose 2 administered at Day 31)
measure: Duration of solicited administration site events
timeFrame: Within 14 days after Dose 1 administration (Dose 1 administered at Day 1)
measure: Duration of solicited administration site events
timeFrame: Within 14 days after Dose 2 administration (Dose 2 administered at Day 31)
measure: Duration of solicited systemic events
timeFrame: Within 14 days after Dose 1 administration (Dose 1 administered at Day 1)
measure: Duration of solicited systemic events
timeFrame: Within 14 days after Dose 2 administration (Dose 2 administered at Day 31)
measure: Percentage of participants with any unsolicited adverse events (AEs)
timeFrame: Within 31 days after Dose 1 administration (Dose 1 administered at Day 1)
measure: Percentage of participants with any unsolicited adverse events (AEs)
timeFrame: Within 31 days after Dose 2 administration (Dose 2 administered at Day 31)
measure: Percentage of participants with serious AEs (SAEs)
timeFrame: Throughout the entire study period (from Day 1 to Day 361)
measure: Percentage of participants with medically attended AEs (MAEs)
timeFrame: Throughout the entire study period (from Day 1 to Day 361)
measure: Percentage of participants with AEs leading to study withdrawal
timeFrame: Throughout the entire study period (from Day 1 to Day 361)
measure: Percentage of participants with potential mediated immune diseases (pIMDs)
timeFrame: Throughout the entire study period (from Day 1 to Day 361)
measure: Percentage of participants with changes from baseline (pre-vaccination, Day 1) in haematology and biochemistry parameters at Day 8
timeFrame: At Day 8
measure: Percentage of participants with changes from baseline (pre-vaccination, Day 1) in haematology and biochemistry parameters at Day 31
timeFrame: At Day 31
measure: Percentage of participants with changes from baseline (pre-vaccination, Day 1) in haematology and biochemistry parameters at Day 38
timeFrame: At Day 38
measure: Percentage of participants with changes from baseline (pre-vaccination, Day 1) in haematology and biochemistry parameters at Day 61
timeFrame: At Day 61
measure: Percentage of participants with abnormal haematology and biochemistry laboratory parameter values at Day 1
timeFrame: At Day 1
measure: Percentage of participants with abnormal haematology and biochemistry laboratory parameter values at Day 8
timeFrame: At Day 8
measure: Percentage of participants with abnormal haematology and biochemistry laboratory parameter values at Day 31
timeFrame: At Day 31
measure: Percentage of participants with abnormal haematology and biochemistry laboratory parameter values at Day 38
timeFrame: At Day 38
measure: Percentage of participants with abnormal haematology and biochemistry laboratory parameter values at Day 61
timeFrame: At Day 61
Secondary outcomes:
measure: Anti-HBs antibody concentrations
timeFrame: At Day 1, Day 31, Day 61 and Day 361
measure: Percentage of participants seroconverted for anti-HBs
timeFrame: At Day 31, Day 61 and Day 361
measure: Percentage of participants seroprotected for anti-HBs
timeFrame: At Day 31, Day 61 and Day 361
Other outcomes:
Locations:
city: Leuven
country: Belgium
facility: GSK Investigational Site
city: Hamburg
country: Germany
facility: GSK Investigational Site
city: Koeln
country: Germany
facility: GSK Investigational Site
city: Magdeburg
country: Germany
facility: GSK Investigational Site
city: Cambridge
country: United Kingdom
facility: GSK Investigational Site
Study officials:
References: