Effects of PINTA 745 in End Stage Renal Disease (ESRD) Patients Who Require Hemodialysis and Have Protein Energy Wasting

Study Overview
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Brief Summary
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This is a pilot study to assess the safety, pharmacokinetics and effectiveness of PINTA 745 or placebo in treating protein energy wasting (PEW) in patients receiving maintenance hemodialysis (MHD).

Detailed Description
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This is a randomized (participants will be assigned by chance to study treatments), double-blind (participants and study personnel will not know the identity of the study treatments), placebo (an inactive substance that is compared with a drug to test whether the drug has a real effect in a clinical trial)-controlled study in patients who receive maintenance hemodialysis. Three participants will receive PINTA 745 for every participant that receives placebo. PINTA 745 or placebo will be taken intravenously once per week following dialysis. The study period will consist of screening, treatment for 12 weeks, and follow up for 8 weeks. Evaluations will be performed to assess the safety, pharmacokinetics (study of what the body does to a drug), pharmacodynamics (study of what a drug does to the body) and effectiveness in treating protein energy wasting (such as increasing muscle size and muscle function) throughout the study.

Official Title
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A Randomized, Double-blind, Pilot Study of PINTA 745, an Anti-myostatin Peptibody, in Patients With End Stage Renal Disease Who Require Maintenance Hemodialysis and Have Protein Energy Wasting

Conditions
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End Stage Renal Disease, Kidney Disease, Protein Energy Wasting

Intervention / Treatment
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* Drug: PINTA 745
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ESRD patient and on outpatient maintenance hemodialysis for ≥ 6 months Adequate dialysis with Kt/V ≥ 1.2 on two occasions within 12 weeks of enrollment Undergoing dialysis at least 3 times per week, on average Serum albumin ≤ 3.8g/dL within 60 days of enrollment Able and willing to provide Informed consent Exclusion Criteria: Presence of an indwelling central vascular catheter Current medical condition that would interfere with ability to perform physical function tests Active infection requiring hospitalization or antibiotics within the past month Major surgery within past 3 months, minor surgery within the past 4 months Dialysis access revision/angioplasty/replacement within the past 2 weeks History of renal transplant, whether or not functional, within 2 years (however, if graft has been removed, patient will be considered eligible) or plans to undergo renal transplantation within 6 months History of neoplasia, except non-melanoma skin cancers, with a 30% probability of recurrence within 12 months Current treatment with appetite stimulants, anabolic steroids or growth hormone Clinically significant heart disease Difficulty swallowing food or liquid If female, currently breast feeding If female, pregnant If female or male, unwilling to use a highly effective method of contraception

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PINTA 745<br> | Drug: PINTA 745<br>* PINTA 745 will be administered once weekly by IV infusion. Cohort dose schedules: 3mg/kg weekly for 12 weeks 3mg/kg for 3 weeks, followed by 1mg/kg for 9 weeks 6mg/kg for 3 weeks, followed by 2mg/kg for 9 weeks<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo will be administered once weekly by IV infusion. Cohort dose schedules: 3mg/kg weekly for 12 weeks 3mg/kg for 3 weeks, followed by 1mg/kg for 9 weeks 6mg/kg for 3 weeks, followed by 2mg/kg for 9 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose and Percent Changes in Lean Body Mass (LBM) | To evaluate the safety, dose-limiting toxicities (DLTs), maximum tolerated dose (MTD) and pharmacokinetics of PINTA 745 and to evaluate percentage change in LBM relative to baseline at 12 weeks, via dual-energy x-ray absorptiometry(DXA) scans, in the group receiving PINTA 745 at the MTD (or if no MTD is reached, at the recommended phase 2 dose) | MTD will be assessed after the last patient in Cohort 1A and Cohort 2A complete 28 days on treatment. LBM will be assessed for comparing baseline to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Muscle Composition - Lean Body Mass (LBM), Appendicular Lean Mass (ALM) and Mid Upper Arm Muscle Circumference (MUAMC) | To evaluate the change in LBM and ALM via CT and dual-energy x-ray absorptiometry (DXA) scans relative to baseline at 12, 16 and 20 weeks. To evaluate change relative to baseline in MUAMC at 5, 9, 16 and 20 weeks. | Baseline through Week 20 | 
| Change in Physical Function | To evaluate change in physical function as measured by the Stair Climbing Power Test (SCPT) and the 6 Minute Walk Test (6MWT) relative to baseline at 5, 9, 12, 16 and 20 weeks | Baseline through Week 20 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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End Stage Renal Disease, ESRD, Maintenance Hemodialysis, Hemodialysis, Dialysis, MHD, Protein Energy Wasting, PEW