Hepatitis, AutoimmunePhase 2NCT03593460
Phase II AutoImmune Hepatitis
A Phase 2 study testing Synthetic PreImplantation Factor in people with Hepatitis, Autoimmune, run by Christopher O'Brien, MD.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Hepatitis, Autoimmune
- What is being tested?
- Synthetic PreImplantation Factor
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 1 Jan 2019to 31 Dec 2019
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- 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)
Show all 16Show fewer
- 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)
About this study
Official title: Phase II, Open Label, Adaptive Design, Multiple Dose Finding Study to Investigate Synthetic PreImplantation Factor (sPIF) in Patients With Autoimmune Hepatitis (AIH)
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.
Read the 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.
- Conditions
- Hepatitis, Autoimmune
- Being tested
- Synthetic PreImplantation Factor
- Medical subject headings
- Hepatitis, Autoimmune
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Synthetic PreImplantation FactorDrug
Also called sPIF
peptide
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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. Receives: 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 Receives: 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 Receives: 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. Receives: Drug: Synthetic PreImplantation Factor |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jul 2018
- Study start1 Jan 2019 (estimated)
- Primary completion1 Nov 2019 (estimated)
- Study completion31 Dec 2019 (estimated)
Why it stopped: BioIncept changed the focus of future drug development
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hepatitis, AutoimmuneStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- Adaptive Design
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Christopher O'Brien, MD
- Sponsor type
- University, hospital or other
- Collaborators
- BioIncept LLC
- Responsible party
- Sponsor-investigator, Christopher O'Brien, MD, University of Miami
- Investigators
- eytan barnea, MD, Principal investigator, BioIncept LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03593460
- Sponsor's protocol ID
- sPIF-US-AIH-002
- Status last verified
- Dec 2018
- First submitted
- 7 Jun 2018
- Last updated
- 3 Jan 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 23829627
Study at a glance
From the registry record, last updated by the sponsor on 3 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II, Open Label, Adaptive Design, Multiple Dose Finding Study to Investigate Synthetic PreImplantation Factor (sPIF) in Patients With Autoimmune Hepatitis (AIH)
- ClinicalTrials.gov ID
- NCT03593460
- Acronym / sponsor ID
- sPIF-US-AIH-002
- Conditions
- Hepatitis, Autoimmune
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: BioIncept changed the focus of future drug development
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Christopher O'Brien, MDUniversity, hospital or other
- Collaborators
- BioIncept LLC
- Study start
- 1 Jan 2019 (estimated)
- Primary completion
- 1 Nov 2019 (estimated)
- Study completion
- 31 Dec 2019 (estimated)
- First posted
- 20 Jul 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 5
- Model description
- Adaptive Design
| Arm | Type | Receives |
|---|---|---|
| sPIF 1 mg/kg (Starting Dose) | Experimental | Drug: Synthetic PreImplantation FactorPatients 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 |
| sPIF 2 mg/kg | Experimental | Drug: Synthetic PreImplantation FactorPatients will be dosed at 2mg/kg sPIF for 14 days assessing safety, tolerability and clinical response based on the effect on ALT levels. |
| sPIF 3 mg/kg | Experimental | Drug: Synthetic PreImplantation FactorPatients 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 |
| sPIF 4 mg/kg | Experimental | Drug: Synthetic PreImplantation FactorPatients 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 |
| sPIF 5 mg/kg | Experimental | Drug: Synthetic PreImplantation FactorPatients 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Synthetic PreImplantation FactorAlso: sPIFpeptide | Drug | sPIF 1 mg/kg (Starting Dose), sPIF 2 mg/kg, sPIF 3 mg/kg, sPIF 4 mg/kg, sPIF 5 mg/kg |
Primary outcome
Evaluate the safety and tolerability of multiple ascending, subcutaneously administered doses of sPIF in patients with autoimmune hepatitis (AIH) by measuring changes in ALT
Time frame: 12 weeks
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
Time frame: 12 weeks
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
Time frame: 12 weeks
No SAE > Grade 3 observed
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jan 2019.
- Results publication: PubMed 23829627Barnea 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
eytan barnea, MD principal investigator
BioIncept LLC
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Synthetic PreImplantation Factor in people with Hepatitis, Autoimmune, run by Christopher O'Brien, MD.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 0 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 3 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Evaluate the safety and tolerability of multiple ascending, subcutaneously administered doses of sPIF in patients with autoimmune hepatitis (AIH) by measuring changes in ALT (time frame: 12 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03593460, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jan 2019.