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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05267262
Recruitment Status : Not yet recruiting
First Posted : March 4, 2022
Last Update Posted : May 10, 2022
Sponsor:
Information provided by (Responsible Party):
River 3 Renal Corp.

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

Condition or disease Intervention/treatment Phase
Alport Syndrome Focal Segmental Glomerulosclerosis Drug: R3R01 Phase 2

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 recessive 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 glomerulosis (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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Estimated Study Start Date : May 15, 2022
Estimated Primary Completion Date : September 15, 2023
Estimated Study Completion Date : December 15, 2023


Arm Intervention/treatment
Experimental: Cohort 1(Alport Syndrome Patients)
R3R01 administered orally as 200 mg tablets twice daily for the first 7 days, followed by 100 mg twice daily for the remaining 77 days
Drug: R3R01
R3R01 administered orally for 12 weeks

Experimental: Cohort 2(Focal Segmental Glomerulosclerosis Patients)
R3R01 administered orally as 200 mg tablets twice daily for the first 7 days, followed by 100 mg twice daily for the remaining 77 days
Drug: R3R01
R3R01 administered orally for 12 weeks




Primary Outcome Measures :
  1. Incidence of adverse events (Safety and Tolerability) [ Time Frame: 12 weeks ]
    Safety and tolerability as determined by the incidence of adverse events (AEs)

  2. 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).


Secondary Outcome Measures :
  1. 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 [ Time Frame: 24 weeks ]
    Change in quality of life as measured by the Short Form SF-36 for adults

  2. 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 [ Time Frame: 24 weeks ]
    Change in quality of life as measured by the pediatric quality of life inventory (PedsQL) for children



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 and during the course of the study.

Exclusion Criteria:

All Patients:

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

    1. Adults: (SBP ≥ 180mmHg and/or DBP ≥ 100mmHg).
    2. Children: ≥ 95th percentile or ≥ 130/80 mm Hg, whichever is lower
  3. Moderate or severe hepatic impairment (Child-Pugh B or 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05267262


Contacts
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Contact: Kathie Gabriel, RN, MFT 610-937-1932 kgabriel@narrowrivermgmt.com
Contact: Guido Magni, MD, PhD magniguido@yahoo.com

Sponsors and Collaborators
River 3 Renal Corp.
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Responsible Party: River 3 Renal Corp.
ClinicalTrials.gov Identifier: NCT05267262    
Other Study ID Numbers: R3R01-ASFSGS-201
First Posted: March 4, 2022    Key Record Dates
Last Update Posted: May 10, 2022
Last Verified: May 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by River 3 Renal Corp.:
FSGS
Kidney Disease
glomeruli
Additional relevant MeSH terms:
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Glomerulosclerosis, Focal Segmental
Nephritis, Hereditary
Syndrome
Disease
Pathologic Processes
Glomerulonephritis
Nephritis
Kidney Diseases
Urologic Diseases
Urogenital Abnormalities
Congenital Abnormalities
Collagen Diseases
Connective Tissue Diseases