Efficacy and Safety Evaluation of DMX-200 in Adult Patients with Focal Segmental Glomerulosclerosis Receiving Angiotensin II Receptor Blocker Therapy
- Trial ID
- 2023-504597-37-00
- Protocol
- DMX-200-301
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this pivotal Phase 3 study is to evaluate the **efficacy** of DMX-200 in adult patients with focal segmental glomerulosclerosis (FSGS) who are receiving an angiotensin II receptor blocker (ARB). This is assessed by measuring changes in urine protein-to-creatinine ratio (PCR) and the estimated glomerular filtration rate (eGFR) slope. These parameters are critical as they provide insights into the progression of kidney disease and the potential of DMX-200 to alter disease trajectory, which is of significant clinical importance in managing FSGS.
Secondary objectives include:
- Evaluating the **safety** and tolerability of DMX-200 in adult and adolescent patients with FSGS receiving an ARB.
- Assessing the effect of DMX-200 on kidney function parameters, including proteinuria, in adult patients with FSGS receiving an ARB.
- In the open-label extension (OLE), assessing the long-term efficacy of DMX-200 in patients with FSGS receiving an ARB.
- Evaluating the long-term effect of DMX-200 on kidney function parameters in the OLE phase.
Participants
The clinical trial involves a total of **216 participants** diagnosed with **focal segmental glomerulosclerosis** (FSGS). The study population includes both male and female subjects, encompassing a wide age range from adolescents to adults. Participants were selected based on specific criteria, including a diagnosis of primary FSGS, genetic FSGS, or FSGS of undetermined cause, with a requirement for biopsy confirmation within the past seven years for certain types. The trial includes individuals who are currently receiving an angiotensin receptor blocker (ARB) at a maximal tolerated dose or are willing to transition to this treatment. Participants' general health status is monitored, with specific attention to maintaining stable dosages of corticosteroids and other relevant medications. Lifestyle considerations such as body weight and body mass index (BMI) are assessed, with adjustments made for those with moderate or severe edema. The trial also includes a vulnerable population, ensuring comprehensive evaluation across diverse demographic groups. Key inclusion criteria focus on maintaining specific urine protein/creatinine ratios and estimated glomerular filtration rates, alongside controlled blood pressure levels. The study aims to evaluate the efficacy and long-term safety of DMX-200 in this patient population.
Plans and Procedures
The clinical trial is a pivotal Phase 3, multicenter, **randomized**, **double-blind**, **placebo-controlled** study designed to evaluate the efficacy and safety of DMX-200 in patients with **focal segmental glomerulosclerosis** (FSGS) who are receiving an **angiotensin II receptor blocker** (ARB). The trial aims to assess the percent change in urine protein/creatinine ratio (PCR) and the slope of estimated glomerular filtration rate (eGFR) following treatment with DMX-200 compared to placebo. The study is expected to run from March 2022 to November 2026, with participant involvement lasting up to 230 days, depending on the treatment period.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as a biopsy-proven diagnosis of FSGS within the past seven years, stable medication regimens, and specific eGFR and blood pressure parameters. Following the screening, participants will be randomized to receive either DMX-200 or a placebo, administered orally. The trial includes multiple follow-up visits to monitor safety and efficacy endpoints, such as changes in urine PCR and eGFR, as well as the incidence of adverse events. The end-of-study visit will conclude the participant's involvement, assessing the long-term safety and tolerability of the treatment.
Participants may be withdrawn from the study early if they experience significant adverse events, fail to adhere to the study protocol, or if their condition worsens significantly. The trial's primary endpoints focus on the percent change in urine PCR and the slope of eGFR, while secondary endpoints include the incidence and severity of adverse events, changes in clinical laboratory evaluations, and the proportion of patients achieving a proteinuria response. The study is not classified as low intervention, given its Phase 3 status and the investigational nature of DMX-200 in the target population.
Treatment
The clinical trial involves the administration of several **experimental medications** and a **placebo**. The primary experimental medication is **Repagermanium**, a polymer-based compound provided in capsule form. It is administered orally with a maximum daily dose of 240 mg and a total maximum dose of 349,440 mg over a treatment period of 208 days. Repagermanium is identified by the sponsor product code DMX-200 and is designated as an orphan drug for this study.
Additional experimental medications include **Losartan**, **Olmesartan Medoxomil**, **Azilsartan Medoxomil**, **Valsartan**, **Irbesartan**, **Telmisartan**, and **Candesartan**. These are all chemical entities classified as angiotensin II receptor blockers (ARBs) and are administered orally. The maximum daily doses for these medications are as follows: Losartan 100 mg, Olmesartan Medoxomil 40 mg, Azilsartan Medoxomil 80 mg, Valsartan 320 mg, Irbesartan 300 mg, Telmisartan 80 mg, and Candesartan 32 mg. Each of these medications has a maximum treatment period of 230 days.
The study also includes a **placebo** capsule, which serves as a comparator treatment. The placebo is administered in a similar manner to the experimental medications, ensuring blinding in the study design. The placebo does not contain any active pharmaceutical ingredients and is used to assess the efficacy and safety of the experimental treatments.
Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the treatment regimen. The trial is designed to evaluate the efficacy of DMX-200 in patients with focal segmental glomerulosclerosis (FSGS) who are receiving an ARB, with a focus on urine protein-to-creatinine ratio (PCR) and estimated glomerular filtration rate (eGFR) slope as primary endpoints.
Efficacy
The efficacy of DMX-200 in the clinical trial will be assessed using specific primary and secondary endpoints. The primary endpoints include the percent change in urine protein-to-creatinine ratio (PCR) based on 24-hour urine collection and the slope of estimated glomerular filtration rate (**eGFR**) following treatment with DMX-200 compared to placebo. These endpoints are designed to evaluate the drug's impact on kidney function in patients with focal segmental glomerulosclerosis (FSGS) who are receiving an angiotensin II receptor blocker (ARB).
Secondary endpoints will further assess the efficacy by examining the incidence and severity of adverse events (AEs) and clinically significant changes in the safety profile, as measured by changes from baseline in clinical laboratory evaluations, electrocardiograms (ECGs), vital signs, and physical examinations. Additionally, the trial will evaluate the proportion of patients achieving a proteinuria response, defined as a complete response or modified partial remission, and the proportion of patients meeting a composite endpoint of worsening kidney function, including the onset of kidney failure, a 40% decline in eGFR from baseline, or death from kidney or cardiovascular causes.
The efficacy parameters will be measured and collected at various timepoints throughout the trial, including during the double-blind period and the open-label extension (OLE) phase. The OLE phase will assess long-term safety and tolerability, with specific endpoints such as the slope of eGFR and percent change in urine PCR from Week 108 (Baseline) at each visit. These assessments will provide comprehensive data on the efficacy and safety of DMX-200 in the target patient population.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Primary FSGS, genetic FSGS, or FSGS of undetermined cause (FSGS-UC) - For adults (≥18 years), the timing of screening. initial diagnosis (biopsy or genetic testing) must be within 7 years prior to Screening. - For adolescents (<18 years), there is no restriction on the timing of the initial diagnosis. NOTES: i) For Primary FSGS and FSGS-UC, the initial diagnosis must be biopsy-proven. The kidney biopsy should include light microscopy with supportive findings on either electron microscopy or immunofluorescence. ii) For Genetic FSGS, no biopsy is required where there is a documented genetic mutation of a podocyte protein associated with FSGS (via genetic testing). iii) All patients should demonstrate a clinical history and disease course consistent with FSGS
- OLE: The patient received blinded IP throughout the duration of the double-blind period up to the Week 104 (EOT – DB) visit (ie, did not prematurely and permanently discontinue the IP).
- Adults (≥18 years) must be either receiving an ARB at the maximal tolerated dose and ≥ 50% of the maximum recommended dose per the product label prior to Screening, or willing to transition to this treatment (including transition from an ACE inhibitor) prior to stabilization. Adolescents (<18 years) must be receiving a dose of an ARB ≥50% of the maximum recommended dose specific to that age group based on the approved product label (typically weight-based dosing).
- If taking corticosteroids, the dosage must be ≤ 10mg / day prednisone (or equivalent) and stable for ≥4 weeks prior to and during both Screening and Stabilization, and there must be no plan to change their corticosteroid treatment regimen during study. Use of inhaled corticosteroids for respiratory diseases or topical corticosteroids for dermatologic purposes are allowed.
- If taking aldosterone inhibitors, mineralocorticoid receptor antagonists, direct renin inhibitors, sodium-glucose co-transporter-2 inhibitors, endothelin receptor antagonists (including dual antagonists) or glucagon-like peptide-1 receptor inhibitors, the dose and regimen must be stable for ≥12 weeks prior to Screening and maintained during Stabilization and patients must have no plan to change their treatment regimen during the study
- Urine protein/creatinine ratio (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 and Qualification
- Estimated glomerular filtration rate (eGFR) at screening: For adults (≥ 18 years): eGFR ≥25 and ≤120 mL/min/1.73 m2 using the CKD Epidemiology Collaboration (CKD-EPI) Creatinine Equation (2009) For adolescent patients (<18 years): eGFR ≥25mL/min/1.73 m2using the Modified Schwartz formula
- 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. For patients with moderate or severe edema, BMI will be calculated based on remission or premorbid weight measured within 3 months prior to Screening, if available. If not available, BMI will be calculated based on the estimated dry weight, based on the Investigator’s clinical judgment
- OLE: Patients who have completed participation in the double-blind period, including the Week 104 visit (including non-responders, those with disease worsening, and those receiving additional FSGS-directed therapies)
- OLE: Estimated GFR at the Week 104 visit: - For adults (≥18 years): eGFR ≥20 mL/min/1.73 m2 using the CKD-EPI Creatinine Equation (2009) - For adolescent patients (<18 years): eGFR ≥20 mL/min/1.73 m2 using the Modified Schwartz formula.
Exclusion Criteria
- Has FSGS secondary to another condition
- OLE: The patient has met the criteria for premature and permanent IP withdrawal as defined in Section 7.1 or study discontinuation as defined in Section 7.2 at Week 104, or prior to the first open-label dose of DMX 200 at Week 108.
- 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).
- OLE: 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.
- History of type 1 diabetes mellitus, or uncontrolled type 2 diabetes mellitus (defined as glycated hemoglobin >8%)
- 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
- Serum potassium levels >5.5 mmol/L at Screening
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) >2 × upper limit of normal at Screening
- Received non-steroid immunosuppressant agents including biological drugs (eg. rituximab), calcineurin inhibitors, cyclophosphamide, azathioprine, or mycophenolate mofetil within the specified timeframe: For adults (≥18 years), within 12 weeks prior to Screening. For adolescents (<18 years), within 7 days prior to Screening
- Received traditional Chinese medicines (TCMs) containing Tripterygium wilfordii and/or its extract or traditional Chinese herbal decoctions or injections within 12 weeks prior to Screening.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Czechia | Not Recruiting | 30 Mar 2022 | 4 |
 Denmark | Not Recruiting | 30 Mar 2022 | 4 |
 France | Not Recruiting | 30 Mar 2022 | 11 |
 Germany | Not Recruiting | 30 Mar 2022 | 11 |
 Italy | Not Recruiting | 30 Mar 2022 | 11 |
 Portugal | Not Recruiting | 30 Mar 2022 | 18 |
 Spain | Not Recruiting | 30 Mar 2022 | 22 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
- | Other | - | ORAL USE | 80 | 230 | SCP64717 |
Placebo capsule | Placebo | N/A | — | — | — | N/A |
- | Other | - | ORAL USE | 320 | 230 | SCP14623 |
Repagermanium | Test | CAPSULE | ORAL USE | 240 | 208 | PRD9313636 |
- | Other | - | ORAL USE | 32 | 230 | SCP17567 |
- | Other | - | ORAL USE | 100 | 230 | SCP20090 |
- | Other | - | ORAL USE | 80 | 230 | SCP22371 |
- | Other | - | ORAL USE | 40 | 230 | SCP16104 |
- | Other | - | ORAL USE | 300 | 230 | SCP19790 |