R3R01 in Alport Syndrome Patients and Primary Steroid-Resistant Focal Segmental Glomerulosclerosis

Phase 1

• 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 disorders; MedDRA version: 21.1Level: PTClassification code 10067757Term: Focal segmental glomerulosclerosisSystem Organ Class: 10038359 - Renal and urinary disorders; Therapeutic area: Not possible to specify

• Registration Number: EUCTR2021-004192-13-FR
• Lead Sponsor: River 3 Renal, Corporation

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2022-06-09
• Last Update Posted: 8 July 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 50

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 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. Blood pressure in the normotensive or hypertensive range.
4. If patient has received a COVID vaccination, the baseline visit must
occur at least one week or more after the second/booster vaccination.
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).
AS Inclusion Criteria (in addition):
6. Male and female patients from age 12 years and older, males and
females with X-Linked AS and males and females with autosomal
recessive AS.
7. Confirmed diagnosis of AS by genetic testing and /or kidney biopsy.
8. UPCR =1.0 g/g.
9. eGFR = 45 mL/min/1.73m2.
10. 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):
11. Male or female patients, 12 to 75 years old at the time of signing the
informed consent.
12. Primary FSGS, i.e. without any identifiable cause, and confirmed by
renal biopsy or documentation of a genetic mutation in a podocyte
protein associated with FSGS.
13. 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.
14. UPCR between 3.5g/g and 12.0g/g.
15. eGFR > 45 mL/min/1.73m2.
16. If taking concomitant ACE 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 subjects under 18? yes
Number of subjects for this age range: 15
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 32
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 3

Exclusion Criteria

All Patients:
1. Uncontrolled diabetes mellitus as evidenced by an HbA1c = 11%.
2. Uncontrolled hypertension
a. Adults: (SBP = 180mmHg 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 9.5.4.6)
4. Presence of any active (i.e., with symptoms) and/or uncontrolled
infection (including COVID).
5. Human immunodeficiency virus (HIV).
6. BMI > 40.
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 noncompliance
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 adequate
contraception as described in Section 13.3.
15. Males who have no sterilization history and whose female partners
have child-bearing potential, must agree to use highly effective method
of contraception 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 Exclusion Criteria (in addition):
16. Kidney disease apart from AS, e.g. diabetic nephropathy or lupus
nephritis.
17. Bardoxolone treatment in the 90 days prior to screening.
FSGS Exclusion Criteria (in addition):
18. Patient has collapsing variant of FSGS on renal biopsy.
19. Patient has FSGS secondary to another condition (e.g. obesity,
cardiovascular, infectious, or autoimmune disorder).
20. Rituximab, cyclophosphamide or abatacept treatment in the 120 days
prior to screening. If taking other chronic immuno-modulatory
medications that are small molecules, the dosage must be stable for 4
weeks prior to screening.
21. If previous Rituximab treatment is greater than 120 days from
screening, CD20 cell count should be within normal limits.
22. If previous other antibody treatment on a stable dose is greater than
120 days from screening, the investigator must deem administration of
study drug to be safe.
23. SGLT2 inhibitors or sparsentan treatment in the 90 days prior to
screening.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified