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A Randomized Phase I Study of a Hepatitis B Antigen Combined With IMP321

Phase 1
Completed
Conditions
Healthy
Interventions
Biological: hepatitis B antigen (without alum) plus IMP321
Biological: hepatitis B antigen alone (without alum)
Biological: Engerix B
Registration Number
NCT00354861
Lead Sponsor
Immutep S.A.S.
Brief Summary

This is a single centre, three single administrations (Days 1, 29 and 57) at increasing doses of IMP321 (3, 10, 30 and 100 µg) in four cohorts of 12 subjects, single blind, randomized study.

Detailed Description

In each cohort, 8 subjects will receive the hepatitis B antigen (10 µg) with IMP321 at one dose, 2 subjects will receive the reference hepatitis B antigen (10 µg) alone with physiological saline and 2 subjects will receive the commercial vaccine Engerix B® (20 µg).

Engerix B® will be administered intramuscularly. The other treatments will be administered subcutaneously.

The four successive cohorts of volunteers will be:

Cohort A:

* 8 subjects treated by hepatitis B antigen (10 µg HbsAg, subtype adw, without alum) with IMP321 (3 µg),

* 2 subjects treated by hepatitis B antigen (10 µg HbsAg, subtype adw, without alum) with physiological saline,

* 2 subjects treated by the commercial hepatitis vaccine Engerix B® (20 µg HBsAg with alum).

If the tolerability of this cohort is acceptable, the following cohort will be done.

Cohort B:

* 8 subjects treated by hepatitis B antigen (10 µg HbsAg, subtype adw, without alum) with IMP321 (10 µg),

* 2 subjects treated by hepatitis B antigen (10 µg HbsAg, subtype adw, without alum) with Physiological saline,

* 2 subjects treated by the commercial hepatitis vaccine Engerix B® (20 µg HBsAg with alum).

If the tolerability of this cohort is acceptable, the following cohort will be done.

Cohort C:

* 8 subjects treated by hepatitis B antigen (10 µg HbsAg, subtype adw, without alum) with IMP321 (30 µg),

* 2 subjects treated by hepatitis B antigen (10 µg HbsAg, subtype adw, without alum) with physiological saline,

* 2 subjects treated by the commercial hepatitis vaccine Engerix B® (20 µg HBsAg with alum).

If the tolerability of this cohort is acceptable, the following cohort will be done.

Cohort D:

* 8 subjects treated by hepatitis B antigen (10 µg HbsAg, subtype adw, without alum) with IMP321 (100 µg),

* 2 subjects treated by hepatitis B antigen (10 µg HbsAg, subtype adw, without alum) with physiological saline

* 2 subjects treated by the commercial hepatitis vaccine Engerix B® (20 µg HBsAg with alum).

Blood samples will be collected on the morning of days 1, 29, 36, 57 and 85 for pharmacodynamic evaluation.

Monitoring for the occurrence of adverse events (AE), changes in physical examination, vital signs (blood pressure, pulse rate, respiration), electrocardiograms (ECG) and clinical laboratory tests (biochemistry, haematology, urinalysis) will be performed before and after each dose of the study drug to assess safety and tolerability.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
48
Inclusion Criteria
  • able to give a written informed consent ;
  • healthy male volunteers aged between 18 and 40 years and post-menopausal healthy women aged between 18 and 55 years;
  • with body mass index (weight/height²) in the range 18 to 30 kg/m²;
  • registered with the French Social Security in agreement with the French Law (Huriet Law : N° 88.1138 - 20.12.88) on biomedical experimentation;
  • able to comply with protocol requirements, including overnight stays, blood and urine sample collections as defined in the protocol;
  • not previously vaccinated for Hepatitis B.
Exclusion Criteria
  • who on direct questioning and physical examination have evidence of any clinically significant acute or chronic disease, including known or suspected HIV, HBV and HCV infection ;
  • with any clinically significant abnormality following review of pre-study laboratory tests and full physical examination ;
  • who have received any experimental drug within the exclusion period defined in the National Register for Healthy Volunteers of the French Ministry of Health ;
  • who forfeit their freedom by administrative or legal award or who were under guardianship ;
  • unwilling to give their informed consent ;
  • who present a positive laboratory test for Hepatitis B surface antigen (HbsAg), HBc antibodies, HIV 1 and 2 antibodies and HCV antibodies ;
  • who have a history of allergy or intolerance to the study drug ;
  • who had a history of serious allergy, asthma, allergic skin rash or sensitivity to any drug ;
  • who are known or suspected alcohol or drug abusers ;
  • who present a positive laboratory test for urine drug screening (opiates, barbiturates, amphetamine, cannabis) ;
  • who undergo surgery or have donated blood within 1 month prior to the start of the study ;
  • who have taken any prescribed or over the counter drug (including antacid drug), with the exception of paracetamol (up to 3 g per day) within 1 week prior to the first dose administration ;
  • who receive any drug known to affect hepatic metabolism like cimetidine, ketoconazole, fluconazole, itraconazole, phenytoin, rifampicin, rifabutin within 1 month prior to the first dose administration ;
  • who receive any drug known to affect renal tubular secretion like probenecid, beta-lactam antibiotics within 2 weeks prior to the first dose administration ;
  • who present any clinical condition or prior therapy which, in the opinion of the investigator, made the subject unsuitable for the study.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Ahepatitis B antigen (without alum) plus IMP321IMP321
Bhepatitis B antigen alone (without alum)Saline
CEngerix BEngerix B
Primary Outcome Measures
NameTimeMethod
To evaluate clinical and laboratory safety and tolerability profiles3 months
Secondary Outcome Measures
NameTimeMethod
To determine T cell response induction efficacy3 months

Trial Locations

Locations (1)

SGS Aster-Cephac

🇫🇷

Paris, France

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