Phase 2 Dose Finding sPIF in Patients With High Panel Reactive Antibodies

Phase II, Open Label Adaptive Design Dose Finding Study to Investigate Effect of Synthetic PreImplantation Factor (sPIF) in Patients With High Panel Reactive Antibodies

This is an open labeled dose finding adaptive design study. Patients with elevated cPRA values, 30-60% will be recruited and administered sPIF injected subcutaneously for 14 doses; one dose on Monday, Wednesday, Friday, or Tuesday, Thursday, Saturday, per individual patient dialysis schedule.

Study Overview

• Status: Withdrawn
• Conditions: Panel Reactive Antibodies
• Intervention / Treatment: Drug: synthetic PreImplantation Factor

Detailed Description

The purpose of this study is to determine the sPIF dose that reduces serum cPRA to <30%, when administered 14 doses. Safety, tolerability, and efficacy will be evaluated at day 42 and and day 84. The suitability of a patient to receive a kidney transplant will also be monitored up to 6 months after Day 84. Safety and tolerability will be assessed at each of the increased doses and throughout the treatment duration. Exploratory analysis of blood indices will be carried out and changes based on history, physical and laboratory exams will be assessed according to the 12 systems.

• Study Type: Interventional
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Outpatient male and females 18-75 years old
• Able and willing to give written informed consent and comply with the requirements of the study protocol
• Calculated panel reactive antibody (cPRA) >30% and <60% with a threshold using mean fluorescent intensity (MFI) of 3,000 or standard fluorescence intensity (SFI) of 60,000 over six months.
• Women who are of childbearing potential must have a negative serum pregnancy test prior to being enrolled in the study and agree to use effective method of contraception throughout the 84-day study.
• Patients on kidney dialysis 3.3 Exclusion Criteria
• Patients not capable of following through the treatment for various reasons as determined by treating physicians
• Pregnant females
• Requiring blood transfusions
• Have an active infection
• Infection with hepatitis C virus (HCV) or hepatitis B virus(HBV) or human immunodeficiency virus (HIV), lack of documentation of treatment of a positive PPD, baseline leukopenia, white blood cell count (WBC) <4.0, thrombocytopenia (platelet count <100,000/mm) or difficult to treat anemia, a hematocrit chronically <25% on intravenous iron and EPO (erythropoietin) therapy
• Active cancer within 5 years
• Significant cardiac or pulmonary disease (including obstructive pulmonary disease)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: NONE

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: synthetic preImplantation factor 1 mg/kg; Patients will be dosed SQ with 14 doses of sPIF	Drug: synthetic PreImplantation Factor; peptide; Other Names: sPIF
EXPERIMENTAL: synthetic preImplantation factor 2 mg/kg; Patients will be dosed SQ with 14 doses of sPIF	Drug: synthetic PreImplantation Factor; peptide; Other Names: sPIF
EXPERIMENTAL: synthetic preImplantation factor 3 mg/kg; Patients will be dosed SQ 14 doses	Drug: synthetic PreImplantation Factor; peptide; Other Names: sPIF
EXPERIMENTAL: synthetic preImplantation factor 4 mg/kg; Patients will be dosed SQ with 14 doses of sPIF	Drug: synthetic PreImplantation Factor; peptide; Other Names: sPIF
EXPERIMENTAL: synthetic preImplantation factor 5 mg/kg; Patients will be dosed SQ with 14 doses of sPIF	Drug: synthetic PreImplantation Factor; peptide; Other Names: sPIF

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the safety and tolerability of multiple ascending, subcutaneously administered doses of sPIF in patients with high panel reactive antibodies (PRA) with no SAEs greater than grade 3	No grade SAE > Grade 3	84 days
Evaluate the pharmacokinetics of sPIF levels in the circulation after multiple ascending, subcutaneously administered doses of sPIF by measurement of sPIF in circulation	sPIF circulating levels are assessed following dialysis and post-first injection at 1, 2, and 4 hours and before last sPIF dose, trough values.	84 days
Evaluate the effect of sPIF on serum cPRA following administration of multiple ascending, subcutaneously administered doses as determined by CPRA levels	Determine cPRA levels	84 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine the percentage of patients in remission ass determined by CPRA less than 30%	Determine cPRA levels as defined by <30% until day 42, and sustained until day 84. Analysis is based on decrease in cPRA percent, median fluorescent intensity (MFI) and standard fluorescent intensity (SFI) analysis.	84 days
Assess number of patients receiving a kidney transplant within 6 months post-day 84 as dertermined by patients being available for kidney transplant	Determine number of patients eligible for kidney transplant	6 months post study drug treatment

Collaborators and Investigators

• Sponsor: Christopher O'Brien, MD
• Collaborators: BioIncept LLC
• Investigators: Principal Investigator: eytan barnea, MD, BioIncept LLC

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): February 1, 2019
• Primary Completion (ANTICIPATED): December 1, 2020
• Study Completion (ANTICIPATED): December 31, 2020

Study Registration Dates

• First Submitted: June 7, 2018
• First Submitted That Met QC Criteria: July 9, 2018
• First Posted (ACTUAL): July 20, 2018

Study Record Updates

• Last Update Posted (ACTUAL): January 3, 2019
• Last Update Submitted That Met QC Criteria: December 31, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Other Study ID Numbers: 20171060; sPIF-US-PRA-001 (OTHER: University of Miami)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No