sPIF CLINICAL STUDY PROTOCOL IN AUTOIMMUNE HEPATITIS

NCT02239562 | Completed Phase 1 Results DMC

• 2 other identifiers: 20140114119219
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 2

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.

Conditions

Autoimmune Hepatitis

Keywords

sPIF; synthetic PreImplantation Factor; Autoimmune; Liver; Hepatitis

Outcome Measures

Primary Outcomes (1)

• Safety/Tolerability Measured by Clinical Laboratory Tests, Metabolics, Cytokines, Anti-PIF Antibody, Periodic Physical Examination, Including Vital Signs Measurements and 12-lead ECG

  Single Ascending Dose (SAD): Adverse events, concomitant medications: Days 1, 2, 3, 5, 8 Vital signs, Physical exams: Days 1, 2, 8 Complete blood counts (CBC), Serum chemistry, Liver function tests, Pharmacokinetics: Days 1, 2, 8 Lipids, Coagulation, Urinalysis, Pregnancy test: Days 1, 8 EKG, chest x-ray (CXR): Days 1 and 8 Multiple Ascending Dose (MAD): Adverse events, concomitant medications: Days 1, 2, 3, 4, 5, 8, 15, 29 Vital signs, Physical exams: Days 1, 2, 3, 4, 5, 8, 15, 29 CBC, Serum chemistry, Liver function tests, Pharmacokinetics: Days 1, 3, 5, 8, 15, 29 Lipids, Coagulation, Urinalysis, Pregnancy test, EKG: Days 1, 5, 29 CXR: Days 1, 29

  29 Day

Secondary Outcomes (1)

• Number of Participants With Anti-sPIF Antibodies and Drug Interactions

  29 Day

Study Arms (6)

SAD sPIF 0.1

EXPERIMENTAL

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

Drug: sPIF; Drug: Placebo

SAD sPIF 0.5

EXPERIMENTAL

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

Drug: sPIF; Drug: Placebo

SAD sPIF 1.0

EXPERIMENTAL

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

Drug: sPIF; Drug: Placebo

MAD sPIF 0.1

EXPERIMENTAL

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

Drug: sPIF; Drug: Placebo

MAD sPIF 0.5

EXPERIMENTAL

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

Drug: sPIF; Drug: Placebo

MAD sPIF 1.0

EXPERIMENTAL

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

Drug: sPIF; Drug: Placebo

Interventions

sPIF DRUG

Also known as: synthetic PreImplantation Factor

MAD sPIF 0.1; MAD sPIF 0.5; MAD sPIF 1.0; SAD sPIF 0.1; SAD sPIF 0.5; SAD sPIF 1.0

Placebo DRUG

Also known as: Ringer's lactated solution

MAD sPIF 0.1; MAD sPIF 0.5; MAD sPIF 1.0; SAD sPIF 0.1; SAD sPIF 0.5; SAD sPIF 1.0

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female, aged from 18 to 70 years old, of non-child bearing potential (to avoid the possibility if antibodies are formed to sPIF this could put the patient at risk for future fertility)
• Females must be either
• Postmenopausal for greater than two years,
• Postmenopausal for less than two years with an follicle stimulating hormone (FSH) level greater \> 40 million international units per milliliter (mIU/mL )
• Or documented as surgically sterile (bilateral tubal ligation, bilateral oophorectomy or post-hysterectomy) at least three months prior to the screening evaluation
• Autoimmune hepatitis as documented by a:
• Pretreatment score ≥15
• Or a post-treatment score of ≥17 on the International Criteria for the Diagnosis of Autoimmune Hepatitis (Appendix 2)
• Treatment with prednisone and/or other oral, immunosuppressive drug(s) must have been stabilized for at least 6 weeks prior to screening for this study.
• Stable ALT levels with a fixed dose of their immunosuppressant medications
• Subjects do not have to have had 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 mofetil equal to/or less 3000 mg per day,

You may not qualify if:

• Any other forms of chronic liver disease.
• 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).
• Subjects 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 subject 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.
• Patient who are expected to receive a change in their immunosuppressant therapies during the protocol.
• Patients who may receive chemotherapeutic agents (e.g., corticosteroids, immunoglobulins and other immune- or cytokine-based therapies) during the study for any other medical condition.

Sponsors & Collaborators

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

Study Sites (2)

Center for Liver Diseases; University of Miami

Miami, Florida, 33136, United States

Location

Chief Scientist, BIOINCEPT, LLC / Chairman, (SIEP) / Director, Ob&Gyn CAMcare Health Center

Cherry Hill, New Jersey, 08003-3157, United States

Location

Related Publications (2)

• Di Simone N, Di Nicuolo F, Marana R, Castellani R, Ria F, Veglia M, Scambia G, Surbek D, Barnea E, Mueller M. Synthetic PreImplantation Factor (PIF) prevents fetal loss by modulating LPS induced inflammatory response. PLoS One. 2017 Jul 12;12(7):e0180642. doi: 10.1371/journal.pone.0180642. eCollection 2017.

  PMID: 28704412 DERIVED

• Barnea ER, Vialard F, Moindjie H, Ornaghi S, Dieudonne MN, Paidas MJ. PreImplantation Factor (PIF*) endogenously prevents preeclampsia: Promotes trophoblast invasion and reduces oxidative stress. J Reprod Immunol. 2016 Apr;114:58-64. doi: 10.1016/j.jri.2015.06.002. Epub 2015 Jul 21.

  PMID: 26257082 DERIVED

MeSH Terms

Conditions

Hepatitis, Autoimmune; Hepatitis

Interventions

preimplantation factor, synthetic; Ringer's Lactate

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Limitations and Caveats

Due to the small number of subjects, formal statistical analysis was not performed.

Results Point of Contact

• Title: Christopher O'Brien
• Organization: University of Miami

CObrien@med.miami.edu

305-243-2329

Study Officials

• Christopher B. O'Brien, MD

  University of Miami

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Clinical Medicine

Study Record Dates

• First Submitted: September 10, 2014
• First Posted: September 12, 2014
• Study Start: November 14, 2014
• Primary Completion: April 25, 2016
• Study Completion: December 29, 2016
• Last Updated: November 20, 2019
• Results First Posted: November 20, 2019

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)