Alport Syndrome, Focal Segmental Glomerulosclerosis
Conditions
Keywords
FSGS, Kidney Disease, glomeruli
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
Interventions
DRUGR3R01
R3R01 administered orally for 12 weeks
Sponsors
River 3 Renal Corp.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
All Patients: 1. 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). 2. 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. 3. If patient has received a COVID vaccination, the baseline visit must occur at least one week or more after the second/booster vaccination. 4. 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. 5. 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). 6. 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): 7. Males and females with X-Linked AS and males and females with autosomal inherited AS. 1. For countries that are enrolling pediatric patients: patients from age 12 years and older. 2. For countries that are not enrolling pediatric patients: patients from age 18 years and older. 8. Confirmed diagnosis of AS by genetic testing and /or kidney biopsy. For patients enrolled in the US who meet all inclusion and
Exclusion criteria
but have not had their diagnosis confirmed by genetic testing or kidney biopsy, the Sponsor will provide for patient's genetic testing. 9. UPCR ≥1.0 g/g. 10. eGFR ≥ 30 mL/min/1.73m2 (using CKD-EPI equation for adults and Bedside Schwartz equation for children). 11. ACEi/ARB therapy at maximum tolerated dose stable for at least 4 weeks prior to enrollment and during the study. Focal Segmental Glomerulosclerosis Patients Inclusion Criteria (in addition): 12. Male or female patients, 1. For countries that are enrolling pediatric patients: 12 to 75 years old at the time of signing the informed consent 2. For countries that are not enrolling pediatric patients: 18 to 75 years old at the time of signing the informed consent 13. Primary FSGS, (without any identifiable cause, and where the FSGS is confirmed by renal biopsy) or FSGS where there is documentation of a genetic mutation in a podocyte protein associated with FSGS. 14. If on steroids, the dose should remain stable for at least 4 weeks prior to enrollment and during the study. Subjects who are steroid-resistant, defined as failure to achieve partial or complete remission, or subjects who experienced adverse events without acceptable clinical benefit after at least 8 weeks of adequate corticosteroid therapy for children and 12 weeks for adults are eligible. 15. UPCR between 1.5g/g and 12.0g/g. 16. eGFR \> 30 mL/min/1.73m2 (using CKD-EPI equation for adults and Bedside Schwartz equation for children). 17. If taking concomitant ACEi and/or ARB treatment, it should remain at a stable dose for at least 4 weeks prior to enrollment and during the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of adverse events (Safety and Tolerability) | 12 weeks | Safety and tolerability as determined by the incidence of adverse events (AEs) |
| Assess change in urine creatinine protein ratio | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Change in quality of life as measured by the Short Form SF-36 for adults |
| 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 as measured by the pediatric quality of life inventory (PedsQL) for children |
Countries
Belgium, France, Germany, Netherlands, United Kingdom, United States
Outcome results
None listed