Study to Evaluate R3R01 in Patients With Alport Syndrome and Patients With Focal Segmental Glomerulosclerosis

• Status: Not yet recruiting
• Trial end date: 2023-12-15
• Target enrollment: 0
• Participant gender: All

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

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: River 3 Renal Corp.
• Collaborator: IQVIA Biotech

Criteria

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).

Alport Syndrome Patients 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.

Focal Segmental Glomerulosclerosis Patients 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.

Exclusion Criteria:

All Patients:

1. Uncontrolled diabetes mellitus as evidenced by an HbA1c ≥ 11%.

2. Uncontrolled hypertension (SBP ≥ 180mmHg and/or DBP ≥ 100mmHg).

3. Severe hepatic impairment (Child-Pugh C).

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 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 adequate contraception

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.

Alport Syndrome Patients 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.

Focal Segmental Glomerulosclerosis Patients 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 sparsen tan treatment in the 90 days prior to screening.