Study of STX-100 in Renal Transplant Patients With Interstitial Fibrosis and Tubular Atrophy (IF/TA)

Randomized Double-Blind, Placebo-Controlled, Single and Multiple Dose, Dose-Escalation Study of STX 100 in Renal Transplant Patients With Biopsy Proven Interstitial Fibrosis and Tubular Atrophy (IF/TA)

This Phase 2 study is a multi-center, randomized, double-blind, placebo-controlled, single followed by multiple dose, dose escalation study designed to evaluate the safety, tolerability, pharmacokinetics, immunogenicity, and impact of STX-100 on gene and protein expression for αvβ6 related and TGF-β-inducible genes (including tubulointerstitial injury, epithelial function, and IF/TA related genes) in renal transplant patients with biopsy.

Study Overview

• Status: Withdrawn
• Conditions: Chronic Allograft Dysfunction
• Intervention / Treatment: Biological: STX-100

• Study Type: Interventional
• Enrollment (Anticipated): 48
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Cambridge, Massachusetts, United States, 02141
      • Stromedix Investigative Site

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:

• Consenting adult patients, 18 (or the legal age of consent) to 65 years old, male or female.
• eGFR ≥ 25 ml/min (Cockcroft-Gault formula).
• Six to 60 months post renal transplant at the initiation of screening.
• Qualifying renal biopsy obtained within 8 weeks prior to randomization with histologic evidence of ≥ Grade 2 IF/TA (Banff score) without morphologic evidence of a treatable etiology (e.g., BK virus nephropathy, chronic obstruction).
• Adequate bone marrow and liver function
• Weight between 40-110 kg.
• Female patients must be surgically sterile, postmenopausal (minimum 1 year without menses and verified by follicular-stimulating hormone [FSH] levels), or agree to use contraception from the time of signing the informed consent form through 16 weeks following the last injection of study medication. Male patients must also agree to use birth control for either themselves or their partner, as appropriate, from the time of signing the informed consent form through 16 weeks following the last injection of study medication.

Exclusion Criteria:

• Recipient of a multi-organ transplant.
• History of T-cell mediated rejection (TCMR) within 3 months prior to randomization.
• Patients who are receiving high dose corticosteroids at the time of screening.
• Histologic evidence of acute TCMR (≥ Banff Grade 1A) on a qualifying renal biopsy for this study. Patients with 'borderline' changes (Banff criteria) on a qualifying renal biopsy are eligible for this study if the Principal Investigator believes treatment for TCMR is not warranted.
• Prior or current histologic evidence of polyomavirus BK virus nephropathy.
• Any histologic finding on the qualifying renal biopsy that the Investigator believes warrants modifying the patient's current therapy.
• Evidence of active tissue invasive cytomegalovirus or Epstein-Barr virus infection.
• History of malignancy, including carcinoma or post-transplant lymphoproliferative disorder.
• History of chronic pulmonary disease or smoker within the past 5 years or more than 15 pack-years exposure.
• Serious local infection or systemic infection within 3 months prior to screening.
• Surgery within 3 months prior to Day 1 (other than minor cosmetic surgery, minor dental procedures, or percutaneous kidney transplant biopsy).
• Positive test for HBsAg, HCV, or HIV antibody at screening.
• Treatment with another investigational drug, investigational device, or approved therapy for investigational use within 1 month prior to dosing.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: STX-100 (0.03mg/kg); 8 patients (6 active and 2 placebo)	Biological: STX-100; SC, single dose followed by multiple dose
Experimental: STX-100 (0.1mg/kg); 8 patients (6 active and 2 placebo)	Biological: STX-100; SC, single dose followed by multiple dose
Experimental: STX-100 (0.3mg/kg); 16 patients (12 active and 4 placebo)	Biological: STX-100; SC, single dose followed by multiple dose
Experimental: STX-100 (1mg/kg); 16 patients (12 active and 4 placebo)	Biological: STX-100; SC, single dose followed by multiple dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety as measured by adverse events	25 weeks from first dosing (per cohort)

Collaborators and Investigators

• Sponsor: Stromedix, Inc.
• Investigators: Study Chair: Bradley Maroni, MD, Stromedix, Inc.

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (Anticipated): October 1, 2011
• Study Completion (Anticipated): December 1, 2011

Study Registration Dates

• First Submitted: April 6, 2009
• First Submitted That Met QC Criteria: April 8, 2009
• First Posted (Estimate): April 9, 2009

Study Record Updates

• Last Update Posted (Estimate): May 23, 2011
• Last Update Submitted That Met QC Criteria: May 20, 2011
• Last Verified: May 1, 2011

More Information

Terms related to this study

• Keywords: kidney transplant; Chronic allograft nephropathy; Renal transplant; Interstitial fibrosis and tubular atrophy; Chronic allograft dysfunction
• Additional Relevant MeSH Terms: Pathologic Processes; Pathological Conditions, Anatomical; Fibrosis; Atrophy
• Other Study ID Numbers: STX-002