A Study of the Efficacy and Safety of DMX-200 in Patients With FSGS Who Are Receiving an ARB

This is a pivotal Phase 3, multicenter, randomized, double-blind, placebo-controlled study of the efficacy and safety of DMX-200 in patients with FSGS. The duration of the double-blind period per patient is estimated to be maximum of 122 weeks, a Screening and Qualification period of between 6 and 14 weeks (including a 4 week period to complete the assessments required for Screening, Titration (if required, up to 4 weeks) and, 6-weeks of Stabilization, a 104-week Treatment period, and up to a 4-week off-treatment Follow-up period. The treatment duration of the OLE period per patient is estimated to be a minimum of 104 weeks (2 years) with a 4-week off-treatment Follow-up period. The total study duration (double-blind period and OLE combined) is currently estimated to be a minimum of 230 weeks.

DOUBLE BLIND PERIOD

Inclusion criteria

• Patients must be 12 to 80 years old
• A diagnosis of primary FSGS, genetic FSGS, or FSGS of undetermined cause. Confirmed by kidney biopsy within 7 years of screening
• Must be either receiving an ARB at the maximal tolerated dose or willing to transition
• If taking corticosteroids, the dosage must be stable for ≥4 weeks prior to Screening and during Stabilization
• 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 Stabilization
• 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.
• Estimated eGFR ≥25 and ≤120 mL/min/1.73 m2 at Screening for adults & eGFR ≥25mL/min/1.73 m2 for adolescent patients (<18 years)
• 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 (patients <18 years of age) at Screening
• Body weight ≥35 kg (all patients) AND a body mass index (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.
• 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:

• Is not of childbearing potential
• If of childbearing potential and beginning at menarche, agrees to use a highly effective method of contraception consistently during the treatment period.
• A male patient with a female partner of childbearing potential is eligible to participate if he agrees to use acceptable contraception
• 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

• Has FSGS secondary to another condition.
• Patients with nephrotic syndrome (>3.5 g/day proteinuria and serum albumin <30 g/L) who have not previously been treated with standard of care FSGS-directed therapies (including steroids).
• History of type 1 diabetes mellitus, or uncontrolled type 2 diabetes mellitus (defined as glycated hemoglobin [HbA1c] >8% at Screening)
• History of lymphoma, leukemia, or any active malignancy within the past 2 years (except for basal cell or squamous cell carcinomas of the skin or cervical carcinoma in situ that have been resected and with no evidence of metastatic disease).
• Active clinically significant hepatobiliary disease.
• Documented history of heart failure (New York Heart Association Class III/IV) or a major adverse cardiac event within 12 weeks prior to Screening.
• Has a physical, medical, or psychological condition, that in the opinion of the Investigator, may interfere with the evaluation the study.
• The patient has a history of alcohol or illicit drug use disorder within 1 year prior to Screening.
• Had a prior organ transplant or stem cell transplant, with the exception of corneal transplant.
• Positive screening assessment for viral hepatitis B surface antigen, or anti-hepatitis C virus (HCV) antibody AND positive HCV RNA, or human immunodeficiency virus 1 and 2.
• Serum potassium levels >5.5 mmol/L at Screening.
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) >2 × upper limit of normal (ULN) at Screening.
• Treatment with non-steroid immunosuppressant agents including biological drugs (e.g. rituximab), calcineurin inhibitors, cyclophosphamide, azathioprine, or mycophenolate mofetil within 12 weeks prior to Screening.
• History of serious side effects or allergic response to an angiotensin II antagonist or has a known sensitivity to any components in the IP.
• Unable to swallow oral medication.
• Prior participation in any Dimerix-sponsored DMX-200 clinical study.
• Participation in a clinical study with an investigational product (IP) 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.
• Are study site personnel directly affiliated with this study and their immediate families

OLE PERIOD

Inclusion criteria

• 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.
• 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
• The patient received blinded Investigational Product throughout the duration of the double-blind period up to the Week 104 visit
• The patient continues to meet the contraceptive requirements

Exclusion criteria

• The patient has met the criteria for permanent IP discontinuation or study discontinuation
• 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.