DMX-200 in Patients With Focal Segmental Glomerulosclerosis

What is the Purpose of this Study?

This study will evaluate an experimental medication called DMX 200 (repagermanium) for people with focal segmental glomerulosclerosis (FSGS). FSGS is a progressive kidney disease in which the filters (glomeruli) of the kidneys become inflamed and damaged by scarring. This makes the filters ‘leaky’ over time and allows protein from the blood to collect in the urine (proteinuria). Treatments that reduce proteinuria are likely to improve the outlook for kidney function. Researchers aim to determine whether DMX-200 reduces proteinuria and slows the loss of kidney function when taken at the same time as an angiotensin II receptor blocker (ARB). ARBs work by reducing blood pressure and improving kidney function. The study will also evaluate the drug’s tolerability and safety, how quickly it is broken down in the body, and how it affects quality of life. Participants will be randomly assigned to receive either DMX 200 or placebo (inactive substance).

Eligibility

DOUBLE BLIND PERIOD
1. Patients must be 12 to 80 years old
2. A diagnosis of primary FSGS, genetic FSGS, or FSGS of undetermined cause. Confirmed by kidney biopsy or documentation of a genetic mutation in a podocyte protein associated with FSGS

DOUBLE BLIND PERIOD

Inclusion Criteria:

1. Patients must be 12 to 80 years old
2. A diagnosis of primary FSGS, genetic FSGS, or FSGS of undetermined cause. Confirmed by kidney biopsy or documentation of a genetic mutation in a podocyte protein associated with FSGS
3. Must be either receiving an ARB at the maximal tolerated dose or willing to transition
4. If taking corticosteroids, the dosage must be stable for ≥4 weeks prior to Screening and during Stablization
5. If taking aldosterone inhibitors, mineralocorticoid receptor antagonists, direct renin inhibitors, sodium-glucose co-transporter-2 (SGLT2) inhibitors, or endothelin receptor antagonists (ERAs, including dual antagonists), the dose and regimen must be stable for ≥12 weeks prior to Screening and during Stablization
6. Urine PCR \>1.5 g/g (\>169.5 mg/mmol) or 24-hour total protein \>1.5 g/day based on 24-hour urine collection during Screening.
7. Estimated GFR ≥25 mL/min/1.73 m2 at Screening
8. Seated blood pressure ≤160/100 mm Hg (mean of 3 values) (patients ≥18 years of age) or between the 5th and 95th percentile for age, sex, and height 29 (patients \<18 years of age) at Screening.
9. Body weight ≥35 kg (all patients) AND a BMI ≤40 kg/m2 (patients ≥18 years of age) or between the 5th and 98th percentile for age and sex (patients \<18 years of age) at Screening.
10. A female patient is eligible to participate if she is not pregnant or planning to become pregnant during the study, not breastfeeding, and at least one of the following conditions applies:
1. Is not of childbearing potential
2. If of childbearing potential and beginning at menarche, agrees to use a highly effective method of contraception consistently during the treatment period.
11. A male patient with a female partner of childbearing potential is eligible to participate if he agrees to use acceptable contraception
12. A patient or parent/legal guardian (as appropriate) who is capable of giving signed informed consent, and where required, the patient is capable of providing assent.

Exclusion Criteria:

1. Has FSGS secondary to another condition.
2. History of type 1 diabetes mellitus, or uncontrolled type 2 diabetes mellitus (defined as glycated hemoglobin \[HbA1c\] \>8%)
3. History of lymphoma, leukemia, or any active malignancy within the past 2 years
4. Active clinically significant hepatobiliary disease.
5. Documented history of heart failure (New York Heart Association Class III/IV) or a major adverse cardiac event within 12 weeks prior to Screening.
6. Has a physical, medical, or psychological condition, that in the opinion of the Investigator, may interfere with the evaluation the study.
7. The patient has a history of alcohol or illicit drug use disorder within 1 year prior to Screening.
8. Had a prior organ transplant or stem cell transplant, with the exception of corneal transplant.
9. Positive screening assessment for viral hepatitis B surface antigen, or anti-hepatitis C virus antibody AND positive HCV RNA, or human immunodeficiency virus 1 and 2.
10. Serum potassium levels \>5.5 mmol/L at Screening.
11. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \>2 × upper limit of normal (ULN) at Screening
12. Treatment with immunosuppressant biological drugs, calcineurin inhibitors, cyclophosphamide, azathioprine, or mycophenolate mofetil within 12 weeks prior to Screening.
13. History of serious side effects or allergic response to an angiotensin II antagonist or has a known sensitivity to any components in the Investigational Product.
14. Unable to swallow oral medication.
15. Prior participation in any Dimerix-sponsored DMX-200 clinical study.
16. Participation in a clinical study with an Investigational Product within 28 days or 5 half-lives (whichever is longer) prior to Screening or plans to participate in another study during the course of this study.
17. Are study site personnel directly affiliated with this study and their immediate families.
OLE PERIOD

Inclusion Criteria:

1. A patient or parent/legal guardian (as appropriate) who is capable of giving signed informed consent, and where required, the patient is capable of providing assent.
2. Patients who have completed participation in the double-blind period, including the Week 104 visit, and who may derive benefit from (continued) treatment with DMX-200, and/or continued follow-up
3. The patient received blinded Investigational Product throughout the duration of the double-blind period up to the Week 104 visit
4. The patient continues to meet the contraceptive requirements

Exclusion Criteria:

1. The patient has met the criteria for permanent IP discontinuation or study discontinuation
2. Any safety concerns identified during the double-blind period which, in the Investigator's opinion, may interfere with the patient's continued participation during the OLE period.

Show less

Where can I participate?

Beverly

More about this Clinical Trial

What is the full name of this clinical trial?

A pivotal Phase 3, multicenter, randomized, double-blind, placebo-controlled study of the efficacy and safety of DMX-200 in patients with focal segmental glomerulosclerosis who are receiving an angiotensin II receptor blocker

Study Details

Disease Type/Condition

Other

Principal Investigator

Kamil, Elaine

Co-Investigators

Dechu Puliyanda, Helen Pizzo, Subbian Karumanchi

Age Group

Both

Phase

III

IRB Number

STUDY00003785

ClinicalTrials.gov ID

NCT05183646

Key Eligibility

ClinicalTrials.gov

How do I learn more about this study?

clinicaltrials@cshs.org