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Trial registered on ANZCTR


Registration number
ACTRN12614001132639
Ethics application status
Approved
Date submitted
7/10/2014
Date registered
23/10/2014
Date last updated
27/11/2018
Date data sharing statement initially provided
27/11/2018
Date results provided
27/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
A phase II study for treatment of proteinuria in patients currently on irbesartan therapy
Scientific title
An open label, Phase II dose escalation and expansion study to evaluate the safety and efficacy of propagermanium (PPG) added to stable angiotensin receptor blocker therapy (irbesartan) for the treatment of patients with proteinuria
Secondary ID [1] 285412 0
Nil Known
Universal Trial Number (UTN)
U1111-1162-3355
Trial acronym
DMX-200
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Proteinuria 293159 0
Condition category
Condition code
Renal and Urogenital 293432 293432 0 0
Kidney disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention is propagermanium (PPG), which is an oral capsule taken three times daily. Participants must be taking stable irbesartan.

This is a dose escalation study, in which each patient receives increasing doses of PPG every 4 weeks (30mg, 60mg, 90mg, 150mg, 240mg per day) until normalisation of proteinuria. Once proteinuria is within the normal range the current dose becomes that patients final dose, and the patient will remain on their final dose for up to a further 8 weeks. The exposure period ranges from 84 days (if proteinuria is normalised at 30mg) though to 168 days (if a patient is escalated through all doses to the maximal dose). Additionally, there is a screening period ranging from 14 to 42 days and a follow-up period of 28 days where the participant is not exposed to propagermanium.
Intervention code [1] 290330 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 293256 0
To determine the safety and tolerability of propagermanium when added to standard irbesartan treatment in patients with proteinuria as assessed by laboratory evaluations, physical examinations and the incidence and severity of AEs throughout the study. Known/possible adverse events for irbesartan and propgermanium include vertigo, loss of strength, fatigue, skin rash, itchiness and loss of appetite for food (common) high blood potassium levels, jaundice, muscle and joint pain (infrequent) and abnormalities in liver and renal function tests (rare). Patients will be assessed by telephone each week they don't visit the clincic for general health and well being. At each visit (every 4 weeks) the patients will have a physical examination for the following body symptoms: General Appearance, Respiratory, Skin (inc. rashes), Cardiovascular, Eyes, Abdomen/ Gastrointestinal, Ears/Nose/ Throat, Musculoskeletal, Head and Neck /Thyroid, Extremities. Physical measurements will include blood pressure (BP), electrocardiogram (ECG), temperature, height, weight, and respiratory rates. The BP, ECG, thermometer, and scales are calibrated automated digital devices. The panel of evaluations from blood and urine samples which will be taken at each visit are:
1. Liver Function and Enzymes: AST, ALT, GGT, LDH, Alkaline phosphatase, Total Bilirubin, Total protein, Albumin
2. Electrolytes: sodium, potassium, calcium, phosphate, chloride, bicarbonate, magnesium
3. Metabolic & Lipids: HbA1c
4. Renal function: creatinine, BUN, uric acid, eGFR, cystatin C.
5. Haematology: Haemoglobin, Haematocrit, Red cell count, Mean Cell volume, White cell count, platelet count
Mid Stream Urine samples:
1. Chemical examination: pH: Protein: Glucose: Ketones: Blood: Leukocyte Esterase: Nitrite: Bilirubin:
2. The microscopic examination Red Blood Cells: White Blood Cells: Epithelial Cells: Casts: Bacteria: Crystals
24-hour urine samples:
1. Quantification of protein and albumin – calculation of PCR and ACR
2. Urinary Biomarkers: Urinary albumin excretion, Urinary protein excretion, urinary PCR, MCP-1, IL-6, IL-8, TGF-beta, CTGF fibrotic growth factor, NGAL.
The test results and observations on examination will be used by the clinician to determine the safety of the therapy.
Timepoint [1] 293256 0
Physical examination and laboratory variables are measured each visit whilst participants are in the study. The participant’s general well-being is measured weekly, either at during a study visit or via the telephone. The duration is dependent on time each participant requires to reach their final dose, with all participants starting on 30mg with incremental increase each month to a maximum dose of 240mg (study period range 98 to 224days)
Secondary outcome [1] 310684 0
To evaluate the effects of propagermanium on urinary protein biomarkers when added to standard irbesartan in patients with proteinuria, as assessed by measurement of change in urine protein/creatinine ratio (PCR), albumin excretion, urine protein excretion, and albumin creatinine ration (ACR).
Timepoint [1] 310684 0
The participant will have blood and urine tests to measure protein biomarkers every 28 days whilst they are in the trial. The duration is dependent on time each participant requires to reach their final dose, with all participants starting on 30mg with incremental increase each month to a maximum dose of 240mg (study period range 98 to 224days).
Secondary outcome [2] 310873 0
To evaluate the effects of propagermanium on urinary biomarkers of inflammation when added to standard irbesartan in patients with proteinuria. The biomarkers measured are MCP-1, IL-6, IL-8, TGF-beta, CTGF fibrotic growth factor and NGAL.
Timepoint [2] 310873 0
The participant will have urine tests to measure biomarkers of inflammation every 28 days whilst they are in the trial. The duration is dependent on time each participant requires to reach their final dose, with all participants starting on 30mg with incremental increase each month to a maximum dose of 240mg (study period range 98 to 224days).
Secondary outcome [3] 310874 0
To evaluate the effects of propagermanium on serum biomarkers when added to standard irbesartan in patients with proteinuria as assessed by measurement of serum creatinine.
Timepoint [3] 310874 0
The participant will have blood tests to measure serum creatinine every 28 days whilst they are in the trial. The duration is dependent on time each participant requires to reach their final dose, with all participants starting on 30mg with incremental increase each month to a maximum dose of 240mg (study period range 98 to 224days).
Secondary outcome [4] 310879 0
To evaluate the effects of propagermanium on plasma concentration of irbesartan, when added to standard irbesartan in patients with proteinuria as assessed by measurement of plasma levels of PPG and Irbesartan at a single collection time point every 4 weeks throughout the trial.
Timepoint [4] 310879 0
The participant will have blood tests to measure the concentration of PPG and irbesartan in the plasma every 28 days whilst they are in the trial. The duration is dependent on time each participant requires to reach their final dose, with all participants starting on 30mg with incremental increase each month to a maximum dose of 240mg (study period range 98 to 224days).

Eligibility
Key inclusion criteria
Capable of providing informed consent.
Women of child bearing potential or men of reproductive potential must be using adequate birth control measures.
Previously diagnosed with protein in the urine and have a protein/creatinine ratio (PCR) of greater than 50 (mg/mmol) based on 24 hour urine collection.
Patients with a defined level of kidney function as follows:
- serum creatinine 115 to 291 micromol/L inclusive for women
- serum creatinine 132 to 309 micromol/L inclusive for men
- or estimated GFR 20-60
Taking stable irbesartan with BP in range of 110/70 to 150/95 mmHg. (Stable is defined as taking the same dose of IRB for at least 90 days prior to baseline).
Liver function tests less than or equal to 2X upper limit of normal
Patients taking a diuretic must be on a stable dose for at least 2 months.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Rapidly progressing proteinuria (rapidly progressing is defined as a trebling of proteinuria over the preceding 3 month period)
Recent gastrointestinal bleeding
Heart disease that is not considered stable
Acute kidney injury within the 3 months before screening
Are receiving any ACE inhibitor, NSAID therapy or spironolactone
Have uncontrolled blood pressure
Required to take drugs that change the immune system (immunosupressants)
HIV infection
Viral Hepatitis B or C, liver infection, liver cirrhosis or any clinically significant liver damage. (Liver function tests > 2X ULN)
Cancer within 3 years (excluding non melanoma skin cancer) or high risk of developing cancer
Major surgery within 3 months of screening or planned during the study period.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is not concealed, all patients fall within the intention to treat group
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
no randomisation
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Each patient has the dose escalated until normalisation of their proteinuria is determined. That patient is then continued on the same dose for up to 8 weeks.
Phase
Phase 2
Type of endpoint/s
Safety
Statistical methods / analysis
This is an exploratory open label, non-randomised observational pharmacological study and as such formal sample size calculations have not been conducted. The total number of up to 60 patients is considered a suitable size to characterise the effect of the drug on reduction in proteinuria.
The analysis sets will be (1) Intent to treat population, (2) Safety population and (3) Efficacy Population. Demographic and Baseline variables will be described by statistical characteristics. Descriptive analyses will be presented for the intention-to-treat population, safety and efficacy population. Primary safety variables will be extent of exposure, adverse events and clinical laboratory evaluations.The study endpoints will be described using statistical characteristics. Categorical data will be described by frequency and percentage; Continuous data will be described by mean, standard deviation, minimum, 1st quartile, median, 3rd quartile and maximum. Also the number of missing and non-missing values will be given.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
3/09/2015
Actual
3/09/2015
Date of last participant enrolment
Anticipated
1/03/2018
Actual
7/11/2016
Date of last data collection
Anticipated
Actual
4/07/2017
Sample size
Target
30
Accrual to date
Final
27
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 3024 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [2] 4386 0
Box Hill Hospital - Box Hill
Recruitment hospital [3] 4387 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [4] 5090 0
Reservoir Private Hospital Day Procedure Centre - Reservoir
Recruitment postcode(s) [1] 10607 0
3050 - Royal Melbourne Hospital
Recruitment postcode(s) [2] 12553 0
3073 - Reservoir
Recruitment postcode(s) [3] 8736 0
3084 - Heidelberg
Recruitment postcode(s) [4] 10606 0
3128 - Box Hill Central

Funding & Sponsors
Funding source category [1] 290019 0
Commercial sector/Industry
Name [1] 290019 0
Dimerix Ltd
Country [1] 290019 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Dimerix Bioscience Pty Ltd
Address
Suite 5, 95 Hay St, Subiaco WA 6008
Country
Australia
Secondary sponsor category [1] 288707 0
None
Name [1] 288707 0
Address [1] 288707 0
Country [1] 288707 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291726 0
Austin Health HREC
Ethics committee address [1] 291726 0
Austin Hospital
145 Studley Rd
Heidelberg
Victoria 3084
Ethics committee country [1] 291726 0
Australia
Date submitted for ethics approval [1] 291726 0
Approval date [1] 291726 0
26/09/2014
Ethics approval number [1] 291726 0
HREC/14/Austin/296

Summary
Brief summary
The study is to investigate the safety and tolerability of propagermanium on patients exhibiting proteinuria and who are already taking standard irbesartan therapy.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 51754 0
Prof David Power
Address 51754 0
Nephrology
Austin Health
Austin Hospital
145 Studley Rd
Heidelberg
Victoria 3084
Country 51754 0
Australia
Phone 51754 0
+61 3 9496 5634
Fax 51754 0
+61 3 9496 5123
Email 51754 0
David.POWER@austin.org.au
Contact person for public queries
Name 51755 0
James Williams
Address 51755 0
Dimerix Bioscience Limited
PO Box 24231
Melbourne VIC 3000
Country 51755 0
Australia
Phone 51755 0
+61 409 050 519
Fax 51755 0
Email 51755 0
james@dimerix.com
Contact person for scientific queries
Name 51756 0
James Williams
Address 51756 0
Dimerix Bioscience Limited
PO Box 24231
Melbourne VIC 3000
Country 51756 0
Australia
Phone 51756 0
+61 409 050 519
Fax 51756 0
Email 51756 0
james@dimerix.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually

Documents added automatically
No additional documents have been identified.