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

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

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).

Study Overview

• Status: Completed
• Conditions: End Stage Renal Disease; Kidney Disease; Protein Energy Wasting
• Intervention / Treatment: Drug: PINTA 745; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 51
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Lakewood, Colorado, United States, 80228
      • Davita Clinical Research
  • Florida
    • Orlando, Florida, United States, 32809
      • Orlando Clinical Research Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Davita Clinical Research
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • San Antonio, Texas, United States, 78215
      • Clinical Advancement Center, PLLC
  • Washington
    • Seattle, Washington, United States, 98104
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; 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
Experimental: PINTA 745	Drug: PINTA 745; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Pinta Biotherapeutics
• Investigators: Study Director: Christopher Haqq, MD, PhD, Pinta Biotherapeutics

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (Actual): November 1, 2015
• Study Completion (Actual): January 1, 2016

Study Registration Dates

• First Submitted: October 7, 2013
• First Submitted That Met QC Criteria: October 7, 2013
• First Posted (Estimate): October 9, 2013

Study Record Updates

• Last Update Posted (Actual): April 11, 2018
• Last Update Submitted That Met QC Criteria: April 10, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: End Stage Renal Disease; ESRD; Dialysis; Hemodialysis; MHD; Protein Energy Wasting; Maintenance Hemodialysis; PEW
• Additional Relevant MeSH Terms: Metabolic Diseases; Urologic Diseases; Renal Insufficiency; Nutrition Disorders; Body Weight; Body Weight Changes; Renal Insufficiency, Chronic; Emaciation; Weight Loss; Kidney Diseases; Kidney Failure, Chronic; Wasting Syndrome; Cachexia
• Other Study ID Numbers: 745-201