Clinical trial NCT05183646: A Study of the Efficacy and Safety of DMX-200 in Patients With FSGS Who Are Receiving an ARB
Official title: 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 (FSGS) Who Are Receiving an Angiotensin II Receptor Blocker (ARB)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: FSGS
Lead sponsor: Dimerix Bioscience Pty Ltd
Sponsor class: INDUSTRY
First posted: 2022-01-10
Enrollment: 286
Sex: ALL
Minimum age (years): 12
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: DMX-200 (repagermanium) is a C-C chemokine receptor type 2 (CCR2) inhibitor that, when administered concurrently with an ARB, is designed to inhibit recruitment of monocytes implicated in the inflammatory chemokine environment of chronic disease. The purpose of this pivotal randomized double-blind study is to investigate the efficacy and safety of DMX-200 120 mg twice daily (BID) compared with placebo over a treatment period of 104 weeks in adult patients with FSGS who are being treated with an ARB. Given the rarity of the disease and the similarities between adults and pediatric patients with FSGS, Dimerix will also investigate the efficacy and safety of DMX 200 in adolescents aged 12 to 17 years. The double-blind period will be followed by an open-label extension (OLE) which aims to assess the long-term efficacy and safety of DMX 200 for up to 2 additional years.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Evaluate the efficacy of DMX-200 in terms of urine PCR in patients with FSGS who are receiving an ARB.
timeFrame: Baseline to Week 35
measure: Evaluate the efficacy of DMX-200 in terms of eGFR slope in patients with FSGS who are receiving an ARB (Analysis at week 35 and Week 104).
timeFrame: Baseline to Week 104
measure: OLE - Assess the long-term safety and tolerability of open-label treatment with DMX-200 in patients with FSGS who are receiving an ARB.
timeFrame: Double-blind baseline to Week 216
Secondary outcomes:
measure: Evaluate the incidence and severity of AEs with treatment of DMX-200 in patients with FSGS who are receiving an ARB.
timeFrame: Baseline to Week 104
measure: To evaluate the effect of DMX-200 on kidney function parameters including proteinuria in patients with FSGS who are receiving an ARB.
timeFrame: Baseline to Week 104
measure: OLE - Assess the long-term efficacy of open-label treatment with DMX-200 in patients with FSGS who are receiving an ARB.
timeFrame: From Week 108 (Baseline) at each visit
measure: OLE - Evaluate the long-term effect of open-label treatment with DMX-200 on kidney function parameters in patients with FSGS who are receiving an ARB.
timeFrame: Double blind baseline to Week 216
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: ACTION3 Investigational Site 4
state: Arizona
city: Northridge
country: United States
facility: ACTION3 Investigational Site 10
state: California
city: Northridge
country: United States
facility: ACTION3 Investigational Site 13
state: California
city: Coral Gables
country: United States
facility: ACTION3 Investigational Site 20
state: Florida
city: Coral Springs
country: United States
facility: ACTION3 Investigational Site 1
state: Florida
city: Evanston
country: United States
facility: ACTION3 Investigational Site 15
state: Illinois
city: Oak Brook
country: United States
facility: ACTION 3 Investigator Site 19
state: Illinois
city: Baltimore
country: United States
facility: ACTION3 Investigational Site 8
state: Maryland
city: Springfield
country: United States
facility: ACTION3 Investigational Site 21
state: Massachusetts
city: Edina
country: United States
facility: ACTION3 Investigational Site 18
state: Minnesota
city: Kansas City
country: United States
facility: ACTION3 Investigational Site 5
state: Missouri
city: Lincoln
country: United States
facility: ACTION3 Investigational Site 17
state: Nebraska
city: Roseburg
country: United States
facility: ACTION3 Investigational Site 12
state: Oregon
city: Spartanburg
country: United States
facility: ACTION3 Investigational Site 9
state: South Carolina
city: Dallas
country: United States
facility: ACTION3 Investigational Site 2
state: Texas
city: Dallas
country: United States
facility: ACTION3 Investigational Site 14
state: Texas
city: Houston
country: United States
facility: ACTION3 Investigational Site 3
state: Texas
city: Webster
country: United States
facility: ACTION3 Investigational Site 16
state: Texas
city: Salt Lake City
country: United States
facility: ACTION3 Investigational Site 7
state: Utah
city: Buenos Aires
country: Argentina
facility: ACTION3 Investigational Site 5
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: ACTION3 Investigational Site 1
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: ACTION3 Investigational Site 4
city: Córdoba
country: Argentina
facility: ACTION3 Investigational Site 2
city: Santa Fe
country: Argentina
facility: ACTION3 Investigational Site 3
city: Brisbane
country: Australia
facility: ACTION3 Investigational Site 1
city: Melbourne
country: Australia
facility: ACTION3 Investigational Site 2
city: Melbourne
country: Australia
facility: Action3 Investigator Site 6
city: Sydney
country: Australia
facility: ACTION3 Investigational Site 4
city: Sydney
country: Australia
facility: ACTION3 Investigational Site 5
city: Sydney
country: Australia
facility: ACTION3 Investigational Site 7
city: Sydney
country: Australia
facility: Action3 Investigator Site 3
city: Botucatu
country: Brazil
facility: ACTION3 Investigational Site 5
city: Recife
country: Brazil
facility: ACTION3 Investigational Site 4
city: Rio De Janeiro
country: Brazil
facility: ACTION3 Investigational Site 1
city: São Paulo
country: Brazil
facility: ACTION3 Investigational Site 2
city: São Paulo
country: Brazil
facility: ACTION3 Investigational Site 3
city: Copenhagen
country: Denmark
facility: ACTION3 Investigational Site 2
city: Kolding
country: Denmark
facility: ACTION3 Investigational Site 1
city: Odense
country: Denmark
facility: ACTION3 Investigational Site 3
city: Bordeaux
country: France
facility: ACTION3 Investigational Site 4
state: Gironde
city: Créteil
country: France
facility: ACTION3 Investigational Site 5
city: Grenoble
country: France
facility: ACTION3 Investigational Site 1
city: Marseille
country: France
facility: ACTION3 Investigational Site 2
city: Montpellier
country: France
facility: ACTION3 Investigational Site 3
city: Paris
country: France
facility: ACTION3 Investigational Site 7
city: Saint-Priest-en-Jarez
country: France
facility: ACTION3 Investigational Site 6
city: Hong Kong
country: Hong Kong
facility: ACTION3 Investigational Site 1
city: Hong Kong
country: Hong Kong
facility: ACTION3 Investigational Site 2
city: Hong Kong
country: Hong Kong
facility: ACTION3 Investigational Site 3
city: Auckland
country: New Zealand
facility: ACTION3 Investigational Site 1
city: Hamilton
country: New Zealand
facility: ACTION3 Investigational Site 2
city: Barcelona
country: Spain
facility: ACTION3 Investigational Site 3
city: Barcelona
country: Spain
facility: ACTION3 Investigational Site 5
city: Córdoba
country: Spain
facility: ACTION3 Investigational Site 7
city: Madrid
country: Spain
facility: ACTION3 Investigational Site 2
city: Madrid
country: Spain
facility: ACTION3 Investigational Site 8
city: Madrid
country: Spain
facility: ACTION3 Investigational Site 9
city: Sevilla
country: Spain
facility: ACTION3 Investigational Site 1
city: Sevilla
country: Spain
facility: ACTION3 Investigational Site 4
city: Kaohsiung
country: Taiwan
facility: ACTION3 Investigational Site 5
city: New Taipei City
country: Taiwan
facility: ACTION3 Investigational Site 2
city: New Taipei City
country: Taiwan
facility: ACTION3 Investigational Site 4
city: Taichung
country: Taiwan
facility: ACTION3 Investigational Site 6
city: Taipei CITY
country: Taiwan
facility: ACTION3 Investigational Site 1
city: Taipei
country: Taiwan
facility: ACTION3 Investigational Site 3
city: Carshalton
country: United Kingdom
facility: ACTION3 Investigational Site 3
city: Glasgow
country: United Kingdom
facility: ACTION3 Investigational Site 6
city: Leicester
country: United Kingdom
facility: ACTION3 Investigational Site 5
city: London
country: United Kingdom
facility: ACTION3 Investigational Site 2
city: Salford
country: United Kingdom
facility: ACTION3 Investigational Site 1
Study officials:
affiliation: Dimerix Bioscience Pty Ltd
name: David Fuller
role: STUDY_DIRECTOR
References: