A Study of RG-012 in Subjects With Alport Syndrome

A Phase 1, Open-Label Study to Evaluate the Safety, Pharmacodynamics, and Pharmacokinetics of RG-012 for Injection, Including Its Effect on Renal microRNA-21, in Subjects With Alport Syndrome

This is a Phase 1, open-label, multi-center study of the safety, pharmacodynamics, and pharmacokinetics of RG-012 administered to subjects with Alport syndrome.

Study Overview

• Status: Completed
• Conditions: Alport Syndrome
• Intervention / Treatment: Drug: RG012

Detailed Description

This is a Phase 1, multi-center study of the safety, pharmacodynamics, and pharmacokinetics of RG-012 administered to subjects with Alport syndrome. During this open-label study, all eligible subjects will receive RG-012. The study consists of two parts (Part A and Part B). During Part A, half of the participants will receive a single dose of RG-012 and half will receive 4 doses of RG-012 (one dose every other week for 6 weeks). All subjects will undergo two renal biopsies, one before and one after receiving RG-012, to assess the effect of RG-012 on the kidney. After completing Part A, subjects will be able to enter Part B of the study. During Part B, all subjects will receive RG-012 every other week for 48 weeks.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • La Mesa, California, United States, 91942
      • eStudySite
    • Los Angeles, California, United States, 90022
      • Academic Medical Research Institute
    • Riverside, California, United States, 92505
      • Apex Research of Riverside
  • Florida
    • Tampa, Florida, United States, 33604
      • Eminence Medical & Clinical Research
  • Texas
    • Cypress, Texas, United States, 77429
      • Houston Nephrology Research
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • Utah Kidney Research Institute
  • Wisconsin
    • Wauwatosa, Wisconsin, United States, 53226
      • Allegiance Research Specialists, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Males or females, ages 18 to 65 years
2. Confirmed diagnosis of Alport syndrome
3. eGFR between 40 and 90 mL/min/1.73m2
4. Proteinuria of at least 300 mg protein/g creatinine
5. For subjects taking an ACE inhibitor or an ARB, the dosing regimen should be stable for at least 30 days prior to screening
6. Willing to comply with contraception requirements

Exclusion Criteria:

1. Causes of chronic kidney disease aside from Alport syndrome (such as diabetic nephropathy, hypertensive nephropathy, lupus nephritis, or IgA nephropathy)
2. End stage renal disease (ESRD) as evidenced by ongoing dialysis therapy or history of renal transportation
3. Any other condition that may pose a risk to the subject's safety and well-being
4. Female subjects who are pregnant or lactating

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RG-012 Single Dose; 1.5 mg/kg RG012 subcutaneous injection	Drug: RG012; RG012 in 0.3% sodium chloride
Experimental: RG012 Every Other Week; 1.5 mg/kg RG012 subcutaneous injections every other week	Drug: RG012; RG012 in 0.3% sodium chloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety - Adverse Events	Incidence and severity of adverse events	8 weeks
Effect of RG-012 on renal microRNA-21 (miR-21)	Change in miR-21 expression in renal tissue	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic (PK) parameter - Cmax	Maximum observed plasma concentration	8 weeks
Pharmacokinetic (PK) parameter - Tmax	Time to maximum observed plasma concentration	8 weeks
Pharmacokinetic (PK) parameter - AUC	Area under the plasma concentration vs. time curve	8 weeks

Collaborators and Investigators

• Sponsor: Genzyme, a Sanofi Company
• Investigators: Study Director: Clinical Sciences & Operations, M.D., Sanofi

Study record dates

Study Major Dates

• Study Start (Actual): December 22, 2017
• Primary Completion (Actual): May 20, 2019
• Study Completion (Actual): May 20, 2019

Study Registration Dates

• First Submitted: October 22, 2017
• First Submitted That Met QC Criteria: December 13, 2017
• First Posted (Actual): December 14, 2017

Study Record Updates

• Last Update Posted (Actual): April 25, 2022
• Last Update Submitted That Met QC Criteria: April 21, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: Nephritis; Kidney disease; Hereditary nephritis; Hereditary kidney disease
• Additional Relevant MeSH Terms: Pathologic Processes; Kidney Diseases; Urologic Diseases; Disease; Urogenital Abnormalities; Congenital Abnormalities; Connective Tissue Diseases; Nephritis; Collagen Diseases; Syndrome; Nephritis, Hereditary
• Other Study ID Numbers: PDY16327; RG012-06 (Other Identifier: Regulus Therapeutics Inc.)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No