Clinical Trials Register

Summary
EudraCT Number:	2021-004174-64
Sponsor's Protocol Code Number:	DMX-200-301
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-12-22
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Spain - AEMPS

A.2

EudraCT number

2021-004174-64

A.3

Full title of the 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 (FSGS) who are receiving an angiotensin II receptor blocker (ARB)

Estudio pivotal de fase III multicéntrico, aleatorizado, doble ciego y comparado con placebo sobre la eficacia y la seguridad de DMX-200 en pacientes con glomeruloesclerosis focal y segmentaria (GEFS) que estén en tratamiento con un antagonista de los receptores de la angiotensina II (ARA-II)

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Efficacy and safety of DMX-200 in patients with focal segmental glomerulosclerosis

Eficacia y seguridad de DMX-200 en paciente con glomeruloesclerosis focal y segmentaria

A.3.2

Name or abbreviated title of the trial where available

ACTION3

A.4.1

Sponsor's protocol code number

DMX-200-301

A.5.4

Other Identifiers

Name:

US FDA PIND Number:

Number:

146154

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Dimerix Bioscience Pty Ltd
B.1.3.4	Country	Australia
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Dimerix Bioscience Pty Ltd
B.4.2	Country	Australia
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Dimerix Bioscience Pty Ltd
B.5.2	Functional name of contact point	Mercedes Salgueira Lazo
B.5.3	Address:
B.5.3.1	Street Address	Avenida Doctor Fedriani 3
B.5.3.2	Town/ city	Sevilla
B.5.3.3	Post code	41009
B.5.3.4	Country	Spain
B.5.4	Telephone number	+34671 569 602
B.5.6	E-mail	mercedes.salgueira.sspa@juntadeandalucia.es

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EMA/OD/103/18
D.3 Description of the IMP
D.3.1	Product name	Repagermanium
D.3.2	Product code	DMX-200
D.3.4	Pharmaceutical form	Capsule
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Repagermanium
D.3.9.2	Current sponsor code	DMX-200
D.3.9.4	EV Substance Code	SUB234202
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	120
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Focal segmental glomerulosclerosis

Glomeruloesclerosis focal y segmentaria

E.1.1.1

Medical condition in easily understood language

Focal segmental glomerulosclerosis

Glomeruloesclerosis focal y segmentaria

E.1.1.2

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	PT
E.1.2	Classification code	10067757
E.1.2	Term	Focal segmental glomerulosclerosis
E.1.2	System Organ Class	10038359 - Renal and urinary disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10016832
E.1.2	Term	Focal & segmental glomerulosclerosis
E.1.2	System Organ Class	10038359 - Renal and urinary disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate the efficacy of DMX-200 in terms of urine PCR and eGFR slope in patients with FSGS who are receiving an ARB

Evaluar la eficacia de DMX-200 en términos del cociente de P/C en orina y pendiente de TFGe en pacientes con GEFS en tratamiento con un ARA

E.2.2

Secondary objectives of the trial

- To evaluate the safety and tolerability of treatment with DMX-200 in patients with FSGS who are receiving an ARB
- To evaluate the effect of DMX-200 on kidney function parameters including proteinuria in patients with FSGS who are receiving an ARB

- Evaluar la seguridad y tolerabilidad del tratamiento con DMX-200 en pacientes con GEFS en tratamiento con un ARA
- Evaluar el efecto de DMX-200 en los parámetros de la función renal, incluida la proteinuria, en pacientes con GEFS en tratamiento con un ARA

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Key Inclusion Criteria:
- A diagnosis of FSGS confirmed by kidney biopsy. NOTE: The biopsy can have been obtained at any time. Diagnosis of FSGS should be based on light microscopy with supportive findings on either electron microscopy or immunofluorescence analysis (preferably both) and the clinical history and disease course consistent with primary FSGS, genetic FSGS, or FSGS of undetermined cause.
- Must be receiving a stable dose of an ARB (irbesartan, losartan, valsartan, candesartan, olmesartan medoxomil, or azilsartan medoxomil) at the maximal tolerated dose and ≥50% of the maximum recommended dose per the product label for 6 weeks prior to Screening, or willing to transition to this treatment during the Titration and Stabilization period.
- If taking corticosteroids, the dosage must be stable for ≥4 weeks prior to Screening and during the Stabilization period, and patients must have no plan to change their treatment regimen during the study.
- If taking aldosterone inhibitors, mineralocorticoid receptor antagonists, direct renin inhibitors, or sodium-glucose co-transporter-2 inhibitors, the dose and regimen must be stable for ≥26 weeks prior to Screening and during the Stabilization period 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.
- Estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2 at Screening and ≥25 mL/min/1.73 m2 at the Qualification visit (Week −1).
- Seated blood pressure ≤160/100 mm Hg (mean of 3 values) at Screening and ≤140/90 mm Hg (mean of 3 values) at the Qualification visit (Week −1).
- Body mass index ≤40 kg/m2 at Screening.

Criterios clave de inclusión:
- Diagnóstico de GEFS confirmado mediante biopsia de riñón. NOTA: La biopsia puede obtenerse en cualquier momento. El diagnóstico de GEFS debe basarse en estudios de microscopia óptica con hallazgos complementarios en análisis de microscopia electrónica o de inmunofluorescencia (preferiblemente ambos) y una anamnesis y evolución de la enfermedad coherentes con la GEFS primaria, la GEFS genética o la GEFS de causa indeterminada.
- Deben estar en tratamiento estable con un ARA (irbesartán, losartán, valsartán, candesartán, olmesartán medoxomil o azilsartán medoxomil) con la dosis máxima tolerada y ≥50 % de la dosis máxima recomendada según la ficha técnica del producto durante 6 semanas antes de la selección, o dispuestos a cambiar a este tratamiento durante el periodo de ajuste de la dosis y estabilización.
- Si el paciente toma corticoesteroides, la dosis debe ser estable durante >4 semanas antes de la selección y durante el periodo de estabilización; asimismo, los pacientes no deben tener previsto cambiar su pauta posológica durante el estudio.
- Si el paciente toma antialdosterónicos, antagonistas de los receptores de mineralocorticoides, inhibidores directos de la renina o inhibidores del cotransportador de sodio-glucosa de tipo 2, la dosis y la pauta posológica deben ser estables durante >26 semanas antes de la selección y durante el periodo de estabilización, y los pacientes no deben tener previsto realizar cambios en su pauta posológica durante el estudio.
- Cociente de proteína-creatinina (P/C) en orina >1,5 g/g (>169,5 mg/mmol) o proteína total de 24 horas >1,5 g/día, según la recogida de orina de 24 horas durante la selección.
- Tasa de filtración glomerular estimada (TFGe) ≥30 ml/min/1,73 m2 en el momento de la selección y ≥25 ml/min/1,73 m2 durante la visita de cualificación (semana –1).
- Tensión arterial en sedestación ≤160/100 mm Hg (media de 3 valores) en la selección y ≤140/90 mm Hg (media de 3 valores) durante la visita de cualificación (semana –1).
- Índice de masa corporal ≤40 kg/m2 durante la selección.

E.4

Principal exclusion criteria

Key Exclusion Criteria:
- Has FSGS secondary to another condition.
- History of type 1 diabetes mellitus, or uncontrolled type 2 diabetes mellitus (defined as glycated hemoglobin >8%), or non-fasting blood glucose >10 mmol/L 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).
- History of jaundice, active hepatitis, or known hepatobiliary disease (except asymptomatic cholelithiasis).
- 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.
- Treatment with immunosuppressant biological drugs, calcineurin inhibitors, cyclophosphamide, azathioprine, or mycophenolate mofetil within 26 weeks prior to Screening
- Patients with <80.0% compliance to ARB treatment during the Stabilization Period (Weeks −6 to −1) of the study, as confirmed at the Qualification visit.

Criterios clave de exclusión:
- Tener GEFS secundaria a otra afección.
- Antecedentes de diabetes de tipo 1 o diabetes de tipo 2 no controlada (definida como glucohemoglobina >8 %) o glucemia en estado posprandial >10 mmol/l durante la selección.
- Antecedentes de linfoma, leucemia o de cualquier neoplasia maligna activa en los últimos 2 años (excepto en el caso de un carcinoma basocelular o epidermoide de la piel o un carcinoma cervicouterino localizado que se hayan extirpado y sin signos de cáncer con metástasis).
- Antecedentes de ictericia, hepatitis activa o enfermedad hepatobiliar conocida (excepto la colelitiasis asintomática).
- Antecedentes documentados de insuficiencia cardíaca (clases III/IV de la Asociación Neoyorquina de Cardiología [New York Heart Association]) o de una complicación cardíaca grave en las 12 semanas previas a la selección.
- Concentraciones de potasio en suero >5,5 mmol/l en el momento de la selección.
- Alanina aminotransferasa (ALAT) y aspartato aminotransferasa (ASAT) >2 veces el límite superior de la normalidad durante la selección.
- Tratamiento con fármacos inmunodepresores biológicos, inhibidores de la calcineurina, ciclofosfamida, azatioprina o micofenolato mofetilo en las 26 semanas previas a la selección.
- Pacientes con un cumplimiento <80,0 % del tratamiento con ARA durante el periodo de estabilización (semanas –6 a –1) del estudio, según se confirme durante la visita de cualificación.

E.5 End points

E.5.1

Primary end point(s)

1. Percent change in urine PCR (based on 24-hour urine collection) following treatment with DMX-200 compared with placebo
2. Slope of eGFR following treatment with DMX-200 compared with placebo

1. Cambio porcentual en el cociente de P/C en orina (basado en la recogida de orina de 24 horas) después del tratamiento con DMX-200 en comparación con el placebo
2. • Pendiente de TFGe después del tratamiento con DMX-200 en comparación con el placebo

E.5.1.1

Timepoint(s) of evaluation of this end point

1. from Baseline to Week 35
2. from Baseline to Week 104

1. desde el inicio hasta la Semana 35
2. desde el inicio hasta la Semana 104

E.5.2

Secondary end point(s)

1. Incidence and severity of AEs following treatment with DMX-200 compared with placebo
2. Incidence of clinically significant changes in the safety profile of patients treated with DMX-200 compared with placebo, as measured by changes from baseline in clinical laboratory evaluations (hematology, coagulation, clinical chemistry, and urinalysis), ECGs, vital signs, and physical examinations
3. Proportion of responders and non-responders following treatment with DMX-200 compared with placebo, defined as:
- Complete response: 24-hour urine PCR reduction to <0.3 g/g [<33.9 mg/mmol]
- Modified partial remission (FPRE): 24-hour urine PCR reduction ≥40% from Baseline and <1.5 g/g [<169.5 mg/mmol]
- No response (failure to meet any response criteria)
4. Proportion of patients on treatment with DMX 200 compared with placebo that meet a composite endpoint of worsening in kidney function, as defined by the onset of kidney failure (initiation of chronic dialysis, kidney transplantation, or a sustained eGFR of <15 mL/min/1.73 m2), a 30% decline in eGFR from Baseline, or death from kidney or cardiovascular causes

1. Incidencia e intensidad de los AA después del tratamiento con DMX-200 en comparación con el placebo
2. Incidencia de alteraciones de importancia clínica en el perfil de toxicidad de los pacientes tratados con DMX-200 en comparación con el tratamiento con placebo, según la medición de los cambios desde el inicio en las evaluaciones analíticas clínicas (hematología, coagulación, bioquímica clínica y análisis de orina), ECG, constantes vitales y exploraciones físicas
3. Proporción de pacientes con respuesta favorable y sin respuesta al tratamiento después del tratamiento con DMX-200 en comparación con placebo, definida como:
- Respuesta completa: reducción del cociente de P/C en orina de 24 horas a <0,3 g/g (<33,9 mg/mmol)
- Remisión parcial modificada (CREG): reducción >40 % del cociente de P/C en orina de 24 horas con respecto al valor inicial y <1,5 g/g (<169,5 mg/mmol)
- Sin respuesta (no cumple ninguno de los criterios de respuesta)
4. Proporción de pacientes en tratamiento con DMX-200 en comparación con placebo que cumplen un criterio de valoración compuesto de empeoramiento de la función renal, definido como inicio de la insuficiencia renal (inicio de diálisis prolongada, trasplante renal o una TFGe constante <15 ml/min/1,73 m2), una disminución del 30 % en la TFGe desde el inicio o la muerte por causas renales o cardiovasculares

E.5.2.1

Timepoint(s) of evaluation of this end point

1 to 4. Throughout study duration

De 1 a 4. Durante todo el estudio

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Australia

Hong Kong

Argentina

Brazil

Denmark

Korea, Republic of

New Zealand

Spain

Taiwan

United Kingdom

United States

France

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

The end of the study is defined as the date of the last visit of the last patient in the study globally.

El final del estudio se define como la fecha de la última visita del último paciente del estudio a nivel mundial.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

263

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

286

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Patients will not receive any additional treatment or medical care from the Sponsor after completion of the study because, until DMX-200 is approved for patients with FSGS, post-study care should not differ from what is normally expected for patients with FSGS. If the study progresses after the first IA, an open-label extension study may, at the Sponsor’s discretion, be offered to patients who have completed the study.

Los pacientes no recibirán ningún tratamiento o atención médica adicional por parte del Promotor tras la finalización del estudio porque, hasta que se apruebe DMX-200 para pacientes con GEFS, la atención posterior al estudio no debe diferir de la que normalmente se espera para los pacientes con GEFS. Si el estudio progresa después de la primera IA, se puede ofrecer un estudio de extensión abierto, a discreción del Promotor, a los pacientes que hayan completado el estudio.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2022-05-26

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-02-23

P. End of Trial
P.	End of Trial Status	Ongoing

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