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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Panel Reactive Antibodies

Intervention / Treatment
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* Drug: synthetic PreImplantation Factor


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: open label, adaptive design, dose finding study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: synthetic preImplantation factor 1 mg/kg<br>Patients will be dosed SQ with 14 doses of sPIF | Drug: synthetic PreImplantation Factor<br>* peptide<br>* Other names: sPIF;|
| Experimental: synthetic preImplantation factor 2 mg/kg<br>Patients will be dosed SQ with 14 doses of sPIF | Drug: synthetic PreImplantation Factor<br>* peptide<br>* Other names: sPIF;|
| Experimental: synthetic preImplantation factor 3 mg/kg<br>Patients will be dosed SQ 14 doses | Drug: synthetic PreImplantation Factor<br>* peptide<br>* Other names: sPIF;|
| Experimental: synthetic preImplantation factor 4 mg/kg<br>Patients will be dosed SQ with 14 doses of sPIF | Drug: synthetic PreImplantation Factor<br>* peptide<br>* Other names: sPIF;|
| Experimental: synthetic preImplantation factor 5 mg/kg<br>Patients will be dosed SQ with 14 doses of sPIF | Drug: synthetic PreImplantation Factor<br>* peptide<br>* Other names: sPIF;|

What is the study measuring?
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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 |