A Phase II, Multi-center, Open-Label Study to Assess Safety, Tolerability, Efficacy and Pharmacokinetics of R3R01 in AS Patients With Uncontrolled Proteinuria on ACE/ARB Inhibition and in Patients With Primary Steroid-Resistant FSGC
Overview
- Phase
- Phase 2
- Intervention
- R3R01
- Conditions
- Alport Syndrome
- Sponsor
- River 3 Renal Corp.
- Enrollment
- 43
- Locations
- 2
- Primary Endpoint
- Assess change in urine creatinine protein ratio
- Status
- Completed
- Last Updated
- 7 months ago
Overview
Brief Summary
This is a Phase 2, Multi-center, Open-Label Study to Assess Safety, Tolerability, Efficacy and Pharmacokinetics of R3R01 in Alport Syndrome Patients with Uncontrolled Proteinuria on ACE/ARB Inhibition and in Patients with Primary Steroid-Resistant Focal Segmental Glomerulosclerosis
Detailed Description
R3R01 is investigational small molecule designed to decrease fat levels in certain cells in the kidney and therefore may improve kidney function and reduce damage in the kidney. This is a single arm open-label study enrolling patients in three cohorts. Cohort 1 will include 5 adult (≥18 y/o) patients from Cohorts 2 and 3 (including at least one patient from Cohort 2 and at least one patient from Cohort 3). Cohort 2 will include approximately 20 male and female patients from 12 years and older with X-linked Alport Syndrome (AS), and male and female patients with autosomal inherited AS. Cohort 3 will include approximately 30 male and female patients from age 12 to 75 years with a biopsy proven diagnosis who present with primary steroid-resistant focal segmental glomerulosclerosis (FSGS) with proteinuria. All eligible patients will be enrolled to receive R3R01 over a treatment period of 12 weeks with a primary efficacy outcome as the percentage change in proteinuria from baseline to the end of treatment (Day 84) in each cohort as a whole
Investigators
Eligibility Criteria
Inclusion Criteria
- •All Patients:
- •Patient is able to communicate well with the investigator, understands and is willing to comply with all requirements of the study, and understands and signs the written informed consent form (ICF).
- •For children to be eligible, one or both parents/legal guardians must sign a parental permission form which provides information contained in the ICF. Children capable of assent must express their willingness to participate by signing an assent form.
- •If patient has received a COVID vaccination, the baseline visit must occur at least one week or more after the second/booster vaccination.
- •Patients who have had active symptoms of COVID within 3 months prior to screening and are now asymptomatic for the last 2 weeks but have tested COVID PCR positive. If a patient is asymptomatic at screening but is COVID positive, then rescreening can occur after a minimum of two weeks.
- •Both female patients, as well as, female partners of male patients who are of child-bearing potential must be willing to not become pregnant for the complete duration of the study (\>180 days) (90 days after the last dose of study medication).
- •Males (including sterilized subjects) whose female partners have child-bearing potential, must agree to use male contraception (condoms) during the period from the time of signing the informed consent form (ICF) through 90 days after the last dose of study drug. They must agree to immediately inform the investigator if their partner becomes pregnant during the study.
- •Alport Syndrome Patients Inclusion Criteria (in addition):
- •Males and females with X-Linked AS and males and females with autosomal inherited AS.
- •For countries that are enrolling pediatric patients: patients from age 12 years and older.
Exclusion Criteria
- •All Patients:
- •Uncontrolled diabetes mellitus as evidenced by an HbA1c ≥ 11%. For Germany: HbA1c ≥ 8.5%.
- •Uncontrolled hypertension
- •Adults: (SBP ≥ 180mmHg and/or DBP ≥ 100mmHg). For Germany: (SBP ≥ 140mmHg and/or DBP ≥ 100mmHg).
- •Children: ≥ 95th percentile or ≥ 130/80 mm Hg, whichever is lower
- •Moderate or severe hepatic impairment (Child-Pugh B or C), except if (a) decreased serum albumin is directly related to the renal disease (resulting in a Child Pugh score of 7), and (b) no other Child-Pugh Score parameters are increased and (c) patient has no liver pathology in medical history.
- •Presence of any active (i.e., with symptoms) and/or uncontrolled infection (including COVID).
- •Presence of Human immunodeficiency virus (HIV).
- •Note - For Germany: BMI \> 35 (Obesity Class II).
- •History of malignancy other than treated basal cell or squamous cell skin cancer within the past 5 years.
Arms & Interventions
Cohort 2 (Alport Syndrome Patients)
R3R01 administered orally as 200 mg tablets twice daily for 84 days.
Intervention: R3R01
Cohort 3 (Focal Segmental Glomerulosclerosis Patients)
R3R01 administered orally as 200 mg tablets twice daily for the 84 days.
Intervention: R3R01
Outcomes
Primary Outcomes
Assess change in urine creatinine protein ratio
Time Frame: 12 weeks
Change from baseline in urine creatinine protein ratio for Cohort 1 (Alport Syndrome patient group) and Cohort 2(Focal Segmental Glomerulosclerosis patient group).
Incidence of adverse events (Safety and Tolerability)
Time Frame: 12 weeks
Safety and tolerability as determined by the incidence of adverse events (AEs)
Secondary Outcomes
- Change in quality-of-life assessment from baseline to end of treatment and to the end of the follow-up period by cohort for children(24 weeks)
- Change in quality-of-life assessment from baseline to end of treatment and to the end of the follow-up period by cohort for adults(24 weeks)