Anti-Hepatitis A Virus, Pharmacokinetics, and Safety of Immune Globulin (Human)
Condition: Anti-Hepatitis A Antibody Levels in Heathy Subjects
MeSH terms: Hepatitis A; Hepatitis
Intervention: Immune Globulin (Human)
Intervention description: A single 0.2 mL/kg IM injection of Immune Globulin (Human) (GamaSTAN) was administered in healthy subjects.
Intervention MeSH terms: Immunoglobulins; Antibodies; gamma-Globulins; Immunoglobulins, Intravenous; Rho(D) Immune Globulin
Phase: Phase 4
Study type: Interventional
Primary purpose: Prevention
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 28.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      This was a single center, open-label, single-arm study in which approximately 28 Hepatitis A
      virus (HAV)-seronegative healthy subjects were enrolled. There was a screening period of up
      to 28 days during which subjects were screened for enrollment in the study.

      Healthy subjects received a single intramuscular (IM) dose of GamaSTAN (0.2 mL/kg), followed
      by a pharmacokinetic (PK) sampling period of 150 days (approximately 5 half-lives). The
      protective levels of anti-HAV antibodies were assessed up to 60 days after the administration
      of GamaSTAN. A PK curve was obtained during the PK sampling period.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male subjects from 18 to 55 years of age, inclusive, or female subjects from 18 to 65
             years of age, inclusive

          2. Subjects with a body mass index (BMI) of 18.5 to 29.9 kg/m2

          3. Body weight greater than or equal to 50 kg at screening

          4. Subjects willing and able to provide written informed consent

          5. Subjects in good health in the judgment of the Investigator, as determined by medical
             history, physical examination, vital signs, ECG and laboratory assessments

          6. A female study subject must meet one of the following criteria:

               1. If a female of childbearing potential - agrees to use one of the accepted
                  contraceptive regimens from at least 30 days prior to study treatment
                  administration and during the entire study duration. An acceptable method of
                  contraception includes one of the following:

                    -  Abstinence from heterosexual intercourse (i.e. when abstinence is the
                       preferred and usual lifestyle of the subject; periodic abstinence is not
                       acceptable)

                    -  Non-estrogen containing hormonal contraceptives (birth control pills,
                       injectable/implant/insertable hormonal birth control products, transdermal
                       patch)

                    -  Intrauterine device without hormones

                    -  Condom with spermicide

                    -  Diaphragm or cervical cap with spermicide

                    -  Vasectomized partner (minimum 6 months since vasectomy prior to study
                       treatment administration)

               2. If a female of non-childbearing potential - should be surgically sterile (i.e.
                  has undergone complete hysterectomy, bilateral oophorectomy, or tubal ligation)
                  or in a menopausal state (at least 1 year without menses prior to study treatment
                  administration)

          7. A male study subject must agree to use one of the accepted contraceptive regimens
             during the entire study duration;

               -  Abstinence from heterosexual intercourse

               -  Female partner with condom with spermicide used by male study subject

               -  Female partner of non-childbearing potential

               -  Male sterilization (if proof of sterilization is not provided, the subject must
                  agree to use one of the above accepted contraceptive methods)

          8. A male study subject must agree not to impregnate a female or donate sperm during the
             entire study duration

        Exclusion Criteria:

          1. Subject vaccinated against HAV, as documented the in medical history at the screening
             visit

          2. Subject with positive anti-HAV antibodies in blood sample at the screening visit

          3. Subject who previously received any type of IG, including HAV IG within the past 12
             months prior to study treatment administration

          4. Subject with prolonged International Normalized Ratio (INR) or activated partial
             thromboplastin time (aPTT) at the screening visit

          5. Subject with a platelet count below 100×109/L at the screening visit

          6. Subject suffering from some acute or chronic medical, surgical or psychiatric
             significant condition or laboratory abnormality at the screening visit or prior to
             study treatment administration that, according to Investigator judgement, may increase
             the risk associated with study participation or study treatment administration, or may
             interfere with the successful completion or interpretation of the study results

          7. Subject with a history of the following: angioedema, cardiac arrhythmia, angina
             pectoris, myocardial infarction, cerebrovascular accident, cardiac failure, thrombotic
             events, embolism, coagulopathy, diabetes mellitus, hyperlipidaemia, nephrotic
             syndrome, acute renal injury, chronic obstructive pulmonary disease, asthma, hepatic
             disease, reticuloendothelial system dysfunction, or nervous system disorder

          8. Subject with known personal or family history of abnormal bleeding episodes

          9. Subject not willing to receive study treatment via IM route of administration or
             unable to receive study treatment via IM route of administration

         10. Subject with cardiovascular risk factors based on medical history: active tobacco
             smoking and/or ongoing diabetes mellitus at the screening visit

         11. Subject with thrombosis risk factors: prolonged immobilization within 2 months prior
             to the screening visit, history of venous or arterial thrombosis, use of estrogens (30
             days prior to the study drug administration), indwelling central vascular catheters
             and hyperviscosity or hypercoagulable states

         12. Subject with known history of hypersensitivity/allergic reaction to blood/plasma
             products

         13. Subject with known selective IgA deficiency (with or without antibodies to IgA)

         14. Subject who received any plasma-derived product infusion within 12 months prior to
             study treatment administration

         15. Subject who received a blood or plasma transfusion within 12 months prior to study
             treatment administration

         16. Subject with systolic blood pressure >140 mmHg or diastolic blood pressure >90 mmHg at
             the screening visit and prior to treatment administration

         17. Subject with anemia (hemoglobin <12 g/dL in women and 13 g/dL in men) at the screening
             visit

         18. Subjects with proteinuria (>1+ on urine dipstick), blood urea nitrogen (BUN) or
             creatinine greater than the upper limit of normal at the screening visit

         19. Subject with liver enzymes (aspartate aminotransferase [AST], alanine aminotransferase
             [ALT] and gamma-glutamyl transferase [GGT]) levels greater than the upper limit of
             normal at screening visit

         20. Subject who received any dose of parenteral, oral, or inhaled corticosteroids,
             immunosuppressants, or immunomodulators within 6 weeks prior to the screening visit

         21. Subject who received any live virus vaccine within five months prior to the screening
             visit

         22. Subject not willing to postpone receiving any live virus vaccines until 6 months after
             receiving IP

         23. Currently receiving any anti-viral treatment, regardless of the route of
             administration

         24. Subject with virus safety laboratory results (serology and/or nucleic acid
             amplification technology [NAT]) indicative of a current infection with hepatitis A
             virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency
             virus (HIV) or parvovirus B19 (B19V) at the screening visit

         25. Participated in another clinical trial within 30 days prior to the screening visit or
             has received any IPs within 3 months prior to the screening visit

         26. Positive urine drug panel testing at the screening visit or prior to study treatment
             administration

         27. Known or suspected abuse of alcohol, opiates, psychotropic agents or other drugs or
             chemical substances; or has done so in the 12 months prior to the screening visit

         28. In the opinion of the Investigator, the subject may have compliance problems with the
             protocol and the procedures of the protocol

         29. Subject who has already been included in a previous group for this clinical study