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

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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Chronic Allograft Dysfunction

Intervention / Treatment
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* Biological: STX-100


Participation Criteria
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Eligibility Criteria
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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.

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: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Renal transplant, Interstitial fibrosis and tubular atrophy, Chronic allograft dysfunction, Chronic allograft nephropathy, kidney transplant