R3R01 in Alport Syndrome Patients and Primary Steroid-Resistant Focal Segmental Glomerulosclerosis
- Conditions
- Alport Syndrome (AS) and Primary Steroid-Resistent FocalSegmental Glomerulosclerosis (FSGS)MedDRA version: 20.0Level: PTClassification code 10001843Term: Alport's syndromeSystem Organ Class: 10010331 - Congenital, familial and genetic disordersMedDRA version: 21.1Level: PTClassification code 10067757Term: Focal segmental glomerulosclerosisSystem Organ Class: 10038359 - Renal and urinary disordersTherapeutic area: Not possible to specify
- Registration Number
- EUCTR2021-004192-13-NL
- Lead Sponsor
- River 3 Renal, Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 50
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.
AS Inclusion Criteria (in addition):
7. Males and females with X-Linked AS and males and females with
autosomal inherited AS.
a. For countries that are enrolling pediatric patients: patients from age
12 years and older.
b. 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 = 45 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 screening. ACEi/ARB dose should remain stable over the
course of the study.
FSGS Inclusion Criteria (in addition):
12. Male or female patients,
a. For countries that are enrolling pediatric patients: 12 to 75 years old
at the time of signing the informed consent
b. 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. Steroid-resistance defined as failure to achieve partial or complete
remission, or experienced adverse events without acceptable clinical
benefit after at least 8 weeks of adequate corticosteroid therapy for
children and 12 weeks for adults.
15. UPCR between 3.5g/g and 12.0g/g.
16. eGFR > 45 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 a minimum of 28 days prior to enrollment and during
the course of the study.
Are the trial subjec
1. Uncontrolled diabetes mellitus as evidenced by an HbA1c = 11%.
For Germany: HbA1c = 8.5%.
2. Uncontrolled hypertension
a. Adults: (SBP = 180mmHg and/or DBP = 100mmHg).
For Germany: (SBP = 140mmHg and/or DBP = 100mmHg).
b. Children: = 95th percentile or = 130/80 mm Hg, whichever is lower,
as defined in Appendix 13.8.
3. Moderate or severe hepatic impairment as per Child Pugh score (See
Section 9.5.4.7), 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.
4. Presence of any active (i.e., with symptoms) and/or uncontrolled
infection (including COVID).
5. Presence of Human immunodeficiency virus (HIV).
6. BMI > 40. For Germany: BMI > 35 (Obesity Class II).
7. History of malignancy other than treated basal cell or squamous cell
skin cancer within the past 5 years.
8. History of alcohol abuse in the last 5 years or currently drinks in
excess of 21 and 14 units per week for males and females, respectively.
9. Received an investigational agent within 30 days or 5 half-lives prior
to screening (whichever is longer).
10. History of non-compliance such that patient is unlikely to be
compliant with study visits, procedures or drug administration.
11. Patient has had an organ transplant, is currently on an organ
transplant waiting list or there is a reasonable possibility that the
patient will have an organ transplant in the 6 months after screening.
12. Participation in an interventional trial within the previous 3 months
prior to screening or concurrent participation in a research trial.
13. Patient is not suitable to participate in the study for any reason
(including, but not limited to co-morbidities, history of non-compliance
with study visits, procedures, or drug administration) in the opinion of
the investigator.
14. Females of childbearing potential (those who are not surgically
sterilized or post-menopausal for at least 1 year) are excluded from
participation in the study unless they agree to use highly effective
contraception as described in Section 13.3.
15. Females that are lactating.
16. History of hypersensitivity to study drug and/or any of its excipients.
17. Patients with hereditary galactose intolerance, total lactase
deficiency or glucose-galactose malabsorption.
18. Required concomitant use of bardoxolone, rituximab, cyclophosphamide,
abatacept, or sparsentan
AS Exclusion Criteria (in addition):
19. Kidney disease apart from AS, e.g., diabetic nephropathy or lupus
nephritis.
20. Use of Bardoxolone or sparsentan treatment in the 30 days prior to
screening. SGLT2 inhibitors are allowed if the patient is on a stable dose
for at least 3 months prior to screening.
FSGS Exclusion Criteria (in addition):
21. Patient has collapsing variant of FSGS on renal biopsy.
22. Patient has FSGS secondary to another condition (e.g., obesity,cardiovascular, infectious, or autoimmune disorder).
23. Use of Rituximab, cyclophosphamide or abatacept treatment in the
120 days prior to screening. If taking other chronic immune-modulatory
medications that are small molecules, the dosage must be stable for 4
weeks prior to screening.
24. If previous Rituximab treatment is greater than 120 days from
screening, CD20 cell count should be within normal limits.
25. If previous other antibody treatment on a stable dose is greater than
120 days from screening, the investigator mu
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method