Conditions: Autoimmune Hepatitis
Keywords: sPIF synthetic PreImplantation Factor Autoimmune Liver Hepatitis
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 36
Healthy volunteers: no

Brief summary:
The purpose of this study is to study the safety and tolerability of synthetic PreImplantation Factor (sPIF) in female patients with autoimmune hepatitis. Autoimmune hepatitis is a disease where the patient's immune system produces an inappropriate immune response against their own liver. PreImplantation Factor is a substance that is secreted by viable fetuses during pregnancy. PIF apparently initiates both maternal tolerance preventing the loss/rejection of the fetus. Synthetic PIF (sPIF) successfully translates PIF endogenous properties to pregnant and non-pregnant immune disorders. sPIF was found to be effective in preclinical models of autoimmunity and transplantation (published). Specifically sPIF protected the liver against immune attack. Toxicity studies (mice, dogs) have shown that high-dose sPIF administration for 2 weeks followed by 2 weeks observation period demonstrated a high safety profile. This study will evaluate the safety, tolerability and the blood level of this synthetic version of this natural compound in the circulation.

Detailed description:
Both sPIF as well as natural PIF appears to orchestrate a complex series of cytokine effects that overall appear to cause return of proper immune function and regulation rather than a nonspecific immune suppression. PIF acts on both the innate and adaptive arms of the immune system in a dynamic, diverse and synergetic manner "per need". In the pregnancy setting, PIF maintains basal immunity required for embryo and maternal survival, and aids in tolerance for self by blocking activated T cells proliferation that would otherwise harm the embryo. The activity of PIF appears to have a dual complementary mode of action that is dependent on whether the immune system is in the basal or the stimulated immune state. The sPIF concentrations that were used are in the same range as those that are present in maternal circulation of viable pregnancy. sPIF targets three major intracellular proteins that pivotal in autoimmune control.

Arms:
arm 1: single ascending dose (SAD) 3 patients with normal liver function tests (LFTs) and 3 patients with abnormal LFTs randomized in a 2:1 ratio (active drug:placebo) as follows: Single subcutaneous (SQ) dose 0.1 mg/kg sPIF or Placebo Day 1 arm 2: single ascending dose (SAD) 3 patients with normal LFTs and 3 patients with abnormal LFTs randomized in a 2:1 ratio (active drug:placebo) as follows: single SQ dose 0.5 mg/kg sPIF or Placebo Day 1 arm 3: single ascending dose (SAD) 3 patients with normal LFTs and 3 patients with abnormal LFTs randomized in a 2:1 ratio (active drug:placebo) as follows: Cohort 3: single SQ dose 1.0 mg/kg sPIF or Placebo Day 1 arm 4: multiple ascending dose (MAD) 3 patients with normal LFTs and 3 patients with abnormal LFTs randomized in a 2:1 ratio (active drug:placebo) to multiple doses of sPIF SQ (one time) 1X day for 5 consecutive days (Days 1 to 5) Cohort 1: SQ 0.1 mg/kg sPIF or Placebo Days 1-5 arm 5: multiple ascending dose (MAD) 3 patients with normal LFTs and 3 patients with abnormal LFTs randomized in a 2:1 ratio (active drug:placebo) to multiple doses of sPIF SQ 1X day for 5 consecutive days (Days 1 to 5) Cohort 1: SQ 0.5 mg/kg sPIF or Placebo Days 1-5 arm 6: multiple ascending dose (MAD) 3 patients with normal LFTs and 3 patients with abnormal LFTs randomized in a 2:1 ratio (active drug:placebo) to multiple doses of sPIF SQ 1X day for 5 consecutive days (Days 1 to 5) Cohort 1: SQ 1.0 mg/kg sPIF or Placebo Days 1-5

Interventions: intervention 1: sPIF intervention 2: Placebo
Intervention descriptions: intervention 1: None intervention 2: None

Protocol document: