search
Back to results

Phase II AutoImmune Hepatitis

Primary Purpose

Hepatitis, Autoimmune

Status
Withdrawn
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Synthetic PreImplantation Factor
Sponsored by
Christopher O'Brien, MD
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatitis, Autoimmune

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Written informed consent must be obtained before any assessment is performed. Patients with a confirmed diagnosis of AIH either Type II or Type II, based on the International Criteria for the Diagnosis of AIH, will be enrolled at screening.

  • Males and females aged from 18 to 75 years old, of non-child bearing potential
  • Females must be either:

Postmenopausal for greater than two years Postmenopausal for less than two years with an FSH level greater > 40mIU/mL Documented as surgically sterile (bilateral tubal ligation, bilateral oophorectomy or post-hysterectomy) at least three months prior to the screening evaluation Or be greater than age 40, does not want more children, is currently using at least one effective method of birth control at the time of screening and agrees to using two effective methods of birth control starting with Study day 0 and through the 42 days duration of the study

• Must have in the judgment of the Investigator, the diagnosis of AIH, or have a score on the International Criteria for the Diagnosis of AIH (Appendix 2) of: Pretreatment score ≥15 Post-treatment score of ≥17

  • Treatment with prednisone and/or other oral, immunosuppressive drug(s) must be stabilized for 6 weeks prior to screening for this study.
  • All patients with an abnormal ALT confirmed by two measurements 2 weeks apart at screening, with the present dose(s) of their immunosuppressant medication(s)
  • Patients do not have to have a documented relapse after completion of an initial course of therapy
  • Permitted concomitant immunosuppressant medications will include:

Azathioprine dose equal to/or less 100 mg per day Budesonide dose equal to/or less 9 mg per day Mycophenolate metil equal to/or less 3000 mg per day Prednisone equal to/or less than 30 mg per day Ursodeoxycholic acid equal to/or less than 1500 mg er day Prograf equal to/or less than 6 mg per day

  • Patients must agree to abstain from alcohol and illicit drugs use during their participation in the study protocol
  • ALT and AST levels greater than 2 times less than five times the upper limit of the normal (reference) range (ULN) and have no clinical or laboratory evidence of hepatic decompensation (i.e., platelets ≥ 100,000/mm, total bilirubin ≤ 1.5 × ULN, prothrombin time ≤ 1.2 × ULN and albumin ≥ 3.0 g/dL) for inclusion.
  • Normal renal function as determined by a serum creatinine

Exclusion criteria

Patients fulfilling any of the following criteria are not eligible for inclusion in this study. No additional exclusions may be applied by the Investigator, to ensure that the study population will be representative of all eligible patients.

  • Any other forms of chronic liver disease that is not under treatment
  • Decompensated liver disease defined on the basis of any one of the following laboratory parameters at the screening evaluation: total bilirubin > 1.5 × ULN, prothrombin time > 1.2 × ULN, platelets ≤ 100,000/mm3, or albumin < 3 g/dL OR current or prior history of clinical hepatic decompensation (e.g., ascites, jaundice, encephalopathy or variceal hemorrhage)
  • Hemoglobin < 11 g/dL at the screening evaluation
  • Serological evidence of infection with HIV upon review of the medical record
  • Evidence of hepatocellular carcinoma (i.e., screening α-fetoprotein > 50 ng/mL or other standard of care measure and ultrasound)
  • Patients with, or a history of clinically significant oncologic, pulmonary, hepatic, gastrointestinal, renal, other cardiovascular, hematologic, metabolic, endocrine, neurologic, immunologic or hematologic illness or any other major medical disorder that, in the judgment of the Investigator, would interfere with patient treatment, assessment or compliance with the protocol or should otherwise preclude their participation in this trial
  • Have received therapy with potentially hepatotoxic drugs within 3 months (90 days) prior to day 1 or are expected to receive such therapy during the study
  • Patients who are expected to receive a change in their immunosuppressant therapies during the protocol
  • Patients who may receive chemotherapeutic agents (e.g. immunoglobulins and other immune- or cytokine-based therapies) during the study for any other medical condition
  • Use of other investigational drugs within 5 half-lives of enrollment, or within 30 days until the expected pharmacodynamic effect has returned to baseline, whichever is longer
  • History of hypersensitivity to study drug or its excipients
  • Hepatitis B and C, infectious hepatitis (documented in medical record may need to repeat prior to enrollment)
  • Tuberculosis (documented in medical record)
  • Primary sclerosing cholangitis, primary biliary cholangitis (documented in medical record and may need to repeat prior to enrollment)
  • Alpha-1 antitrypsin deficiency, hemochromatosis, or Wilson's disease (documented in the medical record)

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm 4

    Arm 5

    Arm Type

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Arm Label

    sPIF 1 mg/kg (Starting Dose)

    sPIF 2 mg/kg

    sPIF 3 mg/kg

    sPIF 4 mg/kg

    sPIF 5 mg/kg

    Arm Description

    Patients will be administered a starting dose of sPIF 1mg/kg (n=10/cohort) for 14 days assessing safety, tolerability and clinical response based on the effect on ALT levels

    Patients will be dosed at 2mg/kg sPIF for 14 days assessing safety, tolerability and clinical response based on the effect on ALT levels.

    Patients will be administered a starting dose of sPIF 3mg/kg (n=10/cohort) for 14 days assessing safety, tolerability and clinical response based on the effect on ALT levels

    Patients will be administered a starting dose of sPIF 4mg/kg (n=10/cohort) for 14 days assessing safety, tolerability and clinical response based on the effect on ALT levels

    Patients will be administered a starting dose of sPIF 5mg/kg (n=10/cohort) for 14 days assessing safety, tolerability and clinical response based on the effect on ALT levels.

    Outcomes

    Primary Outcome Measures

    Evaluate the safety and tolerability of multiple ascending, subcutaneously administered doses of sPIF in patients with autoimmune hepatitis (AIH) by measuring changes in ALT
    Change of ALT from baseline to normal range
    Evaluate the pharmacokinetics of sPIF levels in the circulation after multiple ascending, subcutaneously administered doses of sPIF by normalization of liver enzymes, immunoglobulins, and bilirubin levels
    normalized AST, ALP, GGT, IgG, and bilirubin levels
    Evaluate the safety and tolerability of the increased sPIF dose and treatment duration by no SAEes greater than grade 3
    No SAE > Grade 3 observed

    Secondary Outcome Measures

    Full Information

    First Posted
    June 7, 2018
    Last Updated
    December 31, 2018
    Sponsor
    Christopher O'Brien, MD
    Collaborators
    BioIncept LLC
    search

    1. Study Identification

    Unique Protocol Identification Number
    NCT03593460
    Brief Title
    Phase II AutoImmune Hepatitis
    Official Title
    Phase II, Open Label, Adaptive Design, Multiple Dose Finding Study to Investigate Synthetic PreImplantation Factor (sPIF) in Patients With Autoimmune Hepatitis (AIH)
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    December 2018
    Overall Recruitment Status
    Withdrawn
    Why Stopped
    BioIncept changed the focus of future drug development
    Study Start Date
    January 1, 2019 (Anticipated)
    Primary Completion Date
    November 1, 2019 (Anticipated)
    Study Completion Date
    December 31, 2019 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor-Investigator
    Name of the Sponsor
    Christopher O'Brien, MD
    Collaborators
    BioIncept LLC

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    This is a Phase IIa open label adaptive design dose finding study in male and female patients with autoimmune hepatitis (AIH) with compensated liver function currently under standard of care. The purpose of this study is to evaluate the sPIF dose that normalizes and maintains the serum ALT when given for 14 doses. Autoimmune Hepatitis is disease where the patient's immune system produces an inappropriate immune response against their own liver. PreImplantation factor (PIF) is a substance that is secreted by viable fetuses during pregnancy. PIF 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. Specifically, sPIF protected the liver against immune attack.
    Detailed Description
    The study is an open label, dose finding trial in patients with AIH who have an elevated ALT levels. Patients will be administered a starting dose of sPIF 1mg/kg (n=10/cohort) for 14 days assessing safety, tolerability and clinical response based on the effect on ALT levels until day 84. This will be followed by enrolling (n=10) patients administering 2mg/kg sPIF for 14 days assessing safety, tolerability and clinical response based on the effect on ALT levels until day 84. This be followed by an interim analysis that will determine clinical efficacy by comparing the 1mg and 2mg dose results; testing the decrease in mean ALT percent and determining the number of patients in remission defined as normalized ALT level. The successful cohort will enroll additional patients to enable power analysis. If no significant improvement is observed in the two cohorts, N=10 patients will be enrolled and administered 3mg/kg sPIF for 14 days assessing safety and tolerability. If no significant improvement is noted and safety and tolerability is maintained additional 10 patients will be enrolled at 4mg/kg. Following the same analysis, the maximal dose to be administered will be 5mg/kg.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Hepatitis, Autoimmune

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Sequential Assignment
    Model Description
    Adaptive Design
    Masking
    None (Open Label)
    Allocation
    Non-Randomized
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    sPIF 1 mg/kg (Starting Dose)
    Arm Type
    Experimental
    Arm Description
    Patients will be administered a starting dose of sPIF 1mg/kg (n=10/cohort) for 14 days assessing safety, tolerability and clinical response based on the effect on ALT levels
    Arm Title
    sPIF 2 mg/kg
    Arm Type
    Experimental
    Arm Description
    Patients will be dosed at 2mg/kg sPIF for 14 days assessing safety, tolerability and clinical response based on the effect on ALT levels.
    Arm Title
    sPIF 3 mg/kg
    Arm Type
    Experimental
    Arm Description
    Patients will be administered a starting dose of sPIF 3mg/kg (n=10/cohort) for 14 days assessing safety, tolerability and clinical response based on the effect on ALT levels
    Arm Title
    sPIF 4 mg/kg
    Arm Type
    Experimental
    Arm Description
    Patients will be administered a starting dose of sPIF 4mg/kg (n=10/cohort) for 14 days assessing safety, tolerability and clinical response based on the effect on ALT levels
    Arm Title
    sPIF 5 mg/kg
    Arm Type
    Experimental
    Arm Description
    Patients will be administered a starting dose of sPIF 5mg/kg (n=10/cohort) for 14 days assessing safety, tolerability and clinical response based on the effect on ALT levels.
    Intervention Type
    Drug
    Intervention Name(s)
    Synthetic PreImplantation Factor
    Other Intervention Name(s)
    sPIF
    Intervention Description
    peptide
    Primary Outcome Measure Information:
    Title
    Evaluate the safety and tolerability of multiple ascending, subcutaneously administered doses of sPIF in patients with autoimmune hepatitis (AIH) by measuring changes in ALT
    Description
    Change of ALT from baseline to normal range
    Time Frame
    12 weeks
    Title
    Evaluate the pharmacokinetics of sPIF levels in the circulation after multiple ascending, subcutaneously administered doses of sPIF by normalization of liver enzymes, immunoglobulins, and bilirubin levels
    Description
    normalized AST, ALP, GGT, IgG, and bilirubin levels
    Time Frame
    12 weeks
    Title
    Evaluate the safety and tolerability of the increased sPIF dose and treatment duration by no SAEes greater than grade 3
    Description
    No SAE > Grade 3 observed
    Time Frame
    12 weeks
    Other Pre-specified Outcome Measures:
    Title
    Determine the proportion of patients achieving total remission by normalization of serum ALT levels
    Description
    Normalization in serum ALT levels (Males <45U/L and females <30 U/L)
    Time Frame
    12 weeks
    Title
    Determine the proportion of patients achieving partial remission by obervation of ALT levels greater than 1 but less than 2 the upper limit of normal
    Description
    ALT levels > 1x ULN and <2x ULN
    Time Frame
    12 weeks

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    75 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Written informed consent must be obtained before any assessment is performed. Patients with a confirmed diagnosis of AIH either Type II or Type II, based on the International Criteria for the Diagnosis of AIH, will be enrolled at screening. Males and females aged from 18 to 75 years old, of non-child bearing potential Females must be either: Postmenopausal for greater than two years Postmenopausal for less than two years with an FSH level greater > 40mIU/mL Documented as surgically sterile (bilateral tubal ligation, bilateral oophorectomy or post-hysterectomy) at least three months prior to the screening evaluation Or be greater than age 40, does not want more children, is currently using at least one effective method of birth control at the time of screening and agrees to using two effective methods of birth control starting with Study day 0 and through the 42 days duration of the study • Must have in the judgment of the Investigator, the diagnosis of AIH, or have a score on the International Criteria for the Diagnosis of AIH (Appendix 2) of: Pretreatment score ≥15 Post-treatment score of ≥17 Treatment with prednisone and/or other oral, immunosuppressive drug(s) must be stabilized for 6 weeks prior to screening for this study. All patients with an abnormal ALT confirmed by two measurements 2 weeks apart at screening, with the present dose(s) of their immunosuppressant medication(s) Patients do not have to have a documented relapse after completion of an initial course of therapy Permitted concomitant immunosuppressant medications will include: Azathioprine dose equal to/or less 100 mg per day Budesonide dose equal to/or less 9 mg per day Mycophenolate metil equal to/or less 3000 mg per day Prednisone equal to/or less than 30 mg per day Ursodeoxycholic acid equal to/or less than 1500 mg er day Prograf equal to/or less than 6 mg per day Patients must agree to abstain from alcohol and illicit drugs use during their participation in the study protocol ALT and AST levels greater than 2 times less than five times the upper limit of the normal (reference) range (ULN) and have no clinical or laboratory evidence of hepatic decompensation (i.e., platelets ≥ 100,000/mm, total bilirubin ≤ 1.5 × ULN, prothrombin time ≤ 1.2 × ULN and albumin ≥ 3.0 g/dL) for inclusion. Normal renal function as determined by a serum creatinine Exclusion criteria Patients fulfilling any of the following criteria are not eligible for inclusion in this study. No additional exclusions may be applied by the Investigator, to ensure that the study population will be representative of all eligible patients. Any other forms of chronic liver disease that is not under treatment Decompensated liver disease defined on the basis of any one of the following laboratory parameters at the screening evaluation: total bilirubin > 1.5 × ULN, prothrombin time > 1.2 × ULN, platelets ≤ 100,000/mm3, or albumin < 3 g/dL OR current or prior history of clinical hepatic decompensation (e.g., ascites, jaundice, encephalopathy or variceal hemorrhage) Hemoglobin < 11 g/dL at the screening evaluation Serological evidence of infection with HIV upon review of the medical record Evidence of hepatocellular carcinoma (i.e., screening α-fetoprotein > 50 ng/mL or other standard of care measure and ultrasound) Patients with, or a history of clinically significant oncologic, pulmonary, hepatic, gastrointestinal, renal, other cardiovascular, hematologic, metabolic, endocrine, neurologic, immunologic or hematologic illness or any other major medical disorder that, in the judgment of the Investigator, would interfere with patient treatment, assessment or compliance with the protocol or should otherwise preclude their participation in this trial Have received therapy with potentially hepatotoxic drugs within 3 months (90 days) prior to day 1 or are expected to receive such therapy during the study Patients who are expected to receive a change in their immunosuppressant therapies during the protocol Patients who may receive chemotherapeutic agents (e.g. immunoglobulins and other immune- or cytokine-based therapies) during the study for any other medical condition Use of other investigational drugs within 5 half-lives of enrollment, or within 30 days until the expected pharmacodynamic effect has returned to baseline, whichever is longer History of hypersensitivity to study drug or its excipients Hepatitis B and C, infectious hepatitis (documented in medical record may need to repeat prior to enrollment) Tuberculosis (documented in medical record) Primary sclerosing cholangitis, primary biliary cholangitis (documented in medical record and may need to repeat prior to enrollment) Alpha-1 antitrypsin deficiency, hemochromatosis, or Wilson's disease (documented in the medical record)
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    eytan barnea, MD
    Organizational Affiliation
    BioIncept LLC
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    23829627
    Citation
    Barnea ER, Rambaldi M, Paidas MJ, Mecacci F. Reproduction and autoimmune disease: important translational implications from embryo-maternal interaction. Immunotherapy. 2013 Jul;5(7):769-80. doi: 10.2217/imt.13.59.
    Results Reference
    result

    Learn more about this trial

    Phase II AutoImmune Hepatitis

    We'll reach out to this number within 24 hrs