Resumen

DMX-200 (repagermanium) es un inhibidor del receptor de quimiocinas C-C tipo 2 (CCR2) que, cuando se administra de forma concomitante con un BRA, está diseñado para inhibir el reclutamiento de monocitos implicados en el entorno de quimiocinas inflamatorias de la enfermedad crónica. El propósito de este estudio aleatorizado doble ciego pivotal es investigar la eficacia y seguridad de DMX-200 120 mg dos veces al día (BID) en comparación con placebo durante un período de tratamiento de 104 semanas en pacientes adultos con GESF que reciben tratamiento con un BRA. Dada la rareza de la enfermedad y las similitudes entre adultos y pacientes pediátricos con GESF, Dimerix también investigará la eficacia y seguridad de DMX-200 en adolescentes de 12 a 17 años. El período doble ciego será seguido de una extensión abierta (EA) que tiene como objetivo evaluar la eficacia y seguridad a largo plazo de DMX-200 durante hasta 2 años adicionales.

Descripción detallada

Este es un estudio pivotal de Fase 3, multicéntrico, aleatorizado, doble ciego, controlado con placebo sobre la eficacia y seguridad de DMX-200 en pacientes con GESF. La duración del período doble ciego por paciente se estima en un máximo de 122 semanas: un período de Selección y Calificación de entre 6 y 14 semanas (incluyendo un período de 4 semanas para completar las evaluaciones requeridas en la Selección, Titulación [si se requiere, hasta 4 semanas] y 6 semanas de Estabilización), un período de Tratamiento de 104 semanas y un período de Seguimiento sin tratamiento de hasta 4 semanas. La duración del tratamiento en el período de EA por paciente se estima en un mínimo de 104 semanas (2 años) con un período de Seguimiento sin tratamiento de 4 semanas. La duración total del estudio (período doble ciego y EA combinados) se estima actualmente en un mínimo de 230 semanas.

Elegibilidad

Edad mínima: 12 YearsEdad máxima: 80 YearsSexo: ALL

Criterios de inclusión

DOUBLE BLIND PERIOD
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.
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

Criterios de exclusión

Unable to swallow oral medication.
Prior participation in any Dimerix-sponsored DMX-200 clinical study.
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.
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.
History of serious side effects or allergic response to an angiotensin II antagonist or has a known sensitivity to any components in the IP.
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
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.

Ubicaciones

Centro Medico Dra Laura Maffei Investigacion Clinica Aplicada

Buenos Aires, Argentina

ACTIVE_NOT_RECRUITING

Hospital Italiano de Buenos Aires

Buenos Aires, Argentina

RECRUITING

Organizacion Medica de Investigacion (OMI)

CABA, Argentina

ACTIVE_NOT_RECRUITING

Centro Médico de Nutrición y Diabetes-CENUDIAB

Ciudad Autonoma Buenos Aires, Argentina

ACTIVE_NOT_RECRUITING

Hospital Britanico de Buenos Aires

Ciudad Autonoma Buenos Aires, Argentina

ACTIVE_NOT_RECRUITING

Hospital General de Agudos Dr. Cosme Argerich

Ciudad Autonoma Buenos Aires, Argentina

ACTIVE_NOT_RECRUITING

Clinica Privada Velez Sarsfield

Córdoba, Argentina

ACTIVE_NOT_RECRUITING

Clinica de Nefrologia Urologia y Enf. Cardiovasculares S.A.

Santa Fe, Argentina

RECRUITING

Un Estudio Pivotal de Fase 3, Multicéntrico, Aleatorizado, Doble Ciego, Controlado con Placebo sobre la Eficacia y Seguridad de DMX-200 en Pacientes con Glomeruloesclerosis Segmentaria y Focal (GESF) que Reciben un Bloqueador del Receptor de Angiotensina II (BRA)

Resumen

Descripción detallada

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

DMX-200

Placebo

Ubicaciones

Centro Medico Dra Laura Maffei Investigacion Clinica Aplicada

Hospital Italiano de Buenos Aires

Organizacion Medica de Investigacion (OMI)

Centro Médico de Nutrición y Diabetes-CENUDIAB

Hospital Britanico de Buenos Aires

Hospital General de Agudos Dr. Cosme Argerich

Clinica Privada Velez Sarsfield

Clinica de Nefrologia Urologia y Enf. Cardiovasculares S.A.

Patrocinadores

Contactos

David Fuller

Alisha Smith