Phase II AutoImmune Hepatitis

NCT03593460 | Withdrawn Phase 2 FDA Drug

• 1 other identifier: sPIF-US-AIH-002
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Hepatitis, Autoimmune

Outcome Measures

Primary Outcomes (3)

• 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

  12 weeks

• 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

  12 weeks

• 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

  12 weeks

Other Outcomes (2)

• Determine the proportion of patients achieving total remission by normalization of serum ALT levels

  12 weeks

• 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

  12 weeks

Study Arms (5)

sPIF 1 mg/kg (Starting Dose)

EXPERIMENTAL

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

Drug: Synthetic PreImplantation Factor

sPIF 2 mg/kg

EXPERIMENTAL

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

Drug: Synthetic PreImplantation Factor

sPIF 3 mg/kg

EXPERIMENTAL

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

Drug: Synthetic PreImplantation Factor

sPIF 4 mg/kg

EXPERIMENTAL

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

Drug: Synthetic PreImplantation Factor

sPIF 5 mg/kg

EXPERIMENTAL

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.

Drug: Synthetic PreImplantation Factor

Interventions

Synthetic PreImplantation Factor DRUG

peptide

Also known as: sPIF

sPIF 1 mg/kg (Starting Dose); sPIF 2 mg/kg; sPIF 3 mg/kg; sPIF 4 mg/kg; sPIF 5 mg/kg

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• 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)

Sponsors & Collaborators

• Christopher O'Brien, MD: lead
• BioIncept LLC: collaborator

Related Publications (1)

• 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.

  PMID: 23829627 RESULT

MeSH Terms

Conditions

Hepatitis, Autoimmune

Interventions

preimplantation factor, synthetic

Condition Hierarchy (Ancestors)

Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• eytan barnea, MD

  BioIncept LLC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Model Details: Adaptive Design

Study Record Dates

• First Submitted: June 7, 2018
• First Posted: July 20, 2018
• Study Start: January 1, 2019
• Primary Completion: November 1, 2019
• Study Completion: December 31, 2019
• Last Updated: January 3, 2019

Record last verified: 2018-12