Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12618000910202
Ethics application status
Approved
Date submitted
24/05/2018
Date registered
30/05/2018
Date last updated
16/12/2020
Date data sharing statement initially provided
27/11/2018
Date results information initially provided
3/02/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Study to assess the safety and effectiveness of propagermanium as add-on therapy in FSGS patients who are already taking Irbesartan.
Scientific title
A Phase 2a, Double-blind, Randomised, Placebo-Controlled, Crossover Study Evaluating the Safety and Efficacy of Propagermanium in Patients with Primary Focal Segmental Glomerulosclerosis (FSGS) who are receiving Irbesartan
Secondary ID [1] 294988 0
None
Universal Trial Number (UTN)
DMX-200_202
Trial acronym
ACTION
Linked study record
This study is a follow up study to study ACTRN12614001132639

Health condition
Health condition(s) or problem(s) studied:
Focal Segmental Glomerulosclerosis 308002 0
Condition category
Condition code
Renal and Urogenital 307038 307038 0 0
Kidney disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Progagermanium one capsule orally twice daily for 16 weeks.
Irbesartan to be taken as per patient's usual routine.
Compliance will be measured by drug accountability and completion of a patient diary.
Patients will receive 16 weeks propagermanium and 16 weeks placebo separated by a 6 week washout period
Intervention code [1] 301322 0
Treatment: Drugs
Comparator / control treatment
Placebo one capsule orally twice daily for 16 weeks. The placebo capsules will be identical in appearance to propagermanium capsules and contain lactose monohydrate, magnesium stearate and talc.
Control group
Placebo

Outcomes
Primary outcome [1] 306017 0
To evaluate the safety of the adjunct use of propagermanium in patients with FSGS who are receiving irbesartan. Assessed by monitoring of adverse events and clinical laboratory tests (biochemistry, haematology, urinalysis).
Timepoint [1] 306017 0
43 week study duration. Will compare results from 16 weeks treatment with propagermanium to 16 weeks treatment with placebo (treatments are separated by a 6 week wash out)
Secondary outcome [1] 347333 0
To evaluate the percentage change from baseline (mean of 2 values) in 24-hour protein creatinine ratio (PCR) after 15/16-weeks of treatment (mean of 2 values) with propagermanium as compared to placebo.
Timepoint [1] 347333 0
Eleven 24-hour urine samples over the 43 week duration of the study at week -2, Week -1, Week 8, Week 15, Week 16, Week 22, Week 23, Week 31, Week 38, Week 39, Week 43

Eligibility
Key inclusion criteria
1. Aged 18 to 80 (inclusive) at screening;
2. A diagnosis of primary FSGS confirmed by renal biopsy;
3. Must be receiving a stable dose of 300 mg daily of irbesartan (in any marketed
formulation) for at least 3 months prior to screening, and have no plan to
change treatment regime throughout the study;
4. Patients can be on stable doses of angiotensin converting enzyme inhibitors,
aldosterone inhibitors, direct renin inhibitor and/or sodium-glucose cotransporter-2 inhibitors. However, the dose and regimen must be stable for 3 months prior to screening and must have no plan to change treatment regime throughout the study;
5. If taking immunosuppressive medications (except for rituximab or
cyclophosphamide), must have a stable treatment regime for 3 months prior to
screening and do not have plans to alter the regimen except to maintain
therapeutic immunosuppression or in the event of AEs. Patients who have
received rituximab or cyclophosphamide must have ceased treatment for at
least 6 months prior to screening;
6. Mean of two PCR values (screening and baseline) of equal to or greater than 150 mg/mmol
(1326 mg/g), and within plus or minus 30% of the screening value at the baseline
assessment;
7. Estimated GFR equal to or greater than 25 mL/min/1.73 m2 using chronic kidney disease
epidemiology collaboration (CKD-EPI) formula at screening;
8. Serum potassium levels (screening and baseline) less than 5.5 mmol/L. If either value is 5.5 or above, the patient may receive dietary advice and be retested 1 week later;
9. A female patient is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
• Not of childbearing potential, defined as surgically sterile (documented hysterectomy, bilateral salpingectomy or bilateral oophorectomy) or postmenopausal (no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone [FSH] level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy; however, in the absence of 12 months of amenorrhea, a single
FSH measurement is insufficient.);
• Of childbearing potential and agrees to use a highly effective method of contraception consistently during the treatment period and for at least 60 days after the last dose of investigational product;
10. A male patient with a female partner of childbearing potential is eligible to participate if he agrees to use acceptable contraception during the treatment period and for at least 60 days after the last dose of investigational product and refrains from donating sperm during this period;
11. Have given written informed consent prior to any study procedures being performed.
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Has FSGS secondary to another condition;
2. A history of type 1 diabetes mellitus, diagnosis of type 2 diabetes mellitus prior to FSGS positive renal biopsy, or non-fasting blood glucose greater than 10 mmol/L at screening;
3. A prior organ or stem cell transplant;
4. A major adverse cardiac event within 6 months before screening;
5. Lymphoma, leukaemia, or any malignancy within the past 5 years except for basal cell or squamous cell carcinomas of the skin or cervical carcinoma in situ that have been resected with no evidence of metastatic disease for 3 years;
6. Jaundice, active hepatitis, or known hepatobiliary disease (except asymptomatic cholelithiasis);
7. Alanine aminotransferase and/or aspartate aminotransferase greater than 2 times the upper limit of normal at screening;
8. Participation in any clinical study with an experimental medication or device within 90 days or 5 half-lives (whichever is longer) of screening or have previously participated in a study involving propagermanium;
9. Positive screening assessment for viral hepatitis B surface antigen or hepatitis C virus (HCV) antibody AND positive HCV RNA or human immunodeficiency virus (HIV), or a history of illicit drug injecting;
10. Seated blood pressure of equal to or greater than 160/100 mmHg at screening;
11. Body mass index equal to or greater than 35 kg/m2 at screening;
12. Past hospitalisation for a major depressive episode;
13. Is breast feeding or pregnant;
14. Unable to comply with the study procedures and assessments, including the ability to swallow capsules;
15. Any other disease, physical or psychological condition that the investigator or sponsor believes may contraindicate the use of the investigational medicinal product or affect the interpretation of study results or render the patient at high risk from treatment complications;
16. Are investigator site personnel directly affiliated with this study or their immediate families. Immediate family is defined as a spouse, parent, child or sibling, whether biological or legally adopted.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
central randomisation by phone/fax/computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
Intervention assignment
Crossover
Other design features
None
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
19/09/2018
Actual
20/11/2018
Date of last participant enrolment
Anticipated
25/03/2019
Actual
10/07/2019
Date of last data collection
Anticipated
29/05/2020
Actual
13/07/2020
Sample size
Target
10
Accrual to date
Final
8
Recruitment in Australia
Recruitment state(s)
NSW,QLD,WA,VIC
Recruitment hospital [1] 10991 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [2] 10992 0
Simon Roger Gosford Renal Research - Gosford
Recruitment hospital [3] 11856 0
Box Hill Hospital - Box Hill
Recruitment hospital [4] 11857 0
Epworth Richmond - Richmond
Recruitment hospital [5] 11858 0
Sunshine Coast University Hospital - Birtinya
Recruitment hospital [6] 11859 0
Liverpool Hospital - Liverpool
Recruitment hospital [7] 11860 0
Westmead Hospital - Westmead
Recruitment hospital [8] 11861 0
Sunshine Hospital - St Albans
Recruitment hospital [9] 11862 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [10] 11863 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [11] 15737 0
Linear Clinical Research - Nedlands
Recruitment hospital [12] 15738 0
Melbourne Renal Research Group Pty Ltd - Reservoir
Recruitment postcode(s) [1] 22781 0
3084 - Heidelberg
Recruitment postcode(s) [2] 22782 0
2250 - Gosford
Recruitment postcode(s) [3] 23994 0
3128 - Box Hill
Recruitment postcode(s) [4] 23995 0
3121 - Richmond
Recruitment postcode(s) [5] 23996 0
4575 - Birtinya
Recruitment postcode(s) [6] 23997 0
2170 - Liverpool
Recruitment postcode(s) [7] 23998 0
2145 - Westmead
Recruitment postcode(s) [8] 23999 0
3021 - St Albans
Recruitment postcode(s) [9] 24000 0
2065 - St Leonards
Recruitment postcode(s) [10] 24001 0
4102 - Woolloongabba
Recruitment postcode(s) [11] 29166 0
6009 - Nedlands
Recruitment postcode(s) [12] 29167 0
3073 - Reservoir

Funding & Sponsors
Funding source category [1] 299574 0
Commercial sector/Industry
Name [1] 299574 0
Dimerix Ltd
Country [1] 299574 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Dimerix Ltd
Address
425 Smith St, Fitzroy VIC 3065
Country
Australia
Secondary sponsor category [1] 298888 0
None
Name [1] 298888 0
None
Address [1] 298888 0
NA
Country [1] 298888 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300476 0
Austin Health Human Research Ethics Committee
Ethics committee address [1] 300476 0
145 Studley Rd, Heidelberg VIC 3084,
Ethics committee country [1] 300476 0
Australia
Date submitted for ethics approval [1] 300476 0
30/05/2018
Approval date [1] 300476 0
14/08/2018
Ethics approval number [1] 300476 0
Ethics committee name [2] 300568 0
Bellberry Human Research Ethics Committee
Ethics committee address [2] 300568 0
129 Glen Osmond Road
Eastwood South Australia 5063
Ethics committee country [2] 300568 0
Australia
Date submitted for ethics approval [2] 300568 0
13/06/2018
Approval date [2] 300568 0
13/07/2018
Ethics approval number [2] 300568 0

Summary
Brief summary
Eligible patients will randomly assigned (50/50 chance) to receive both the propagermanium and placebo in different orders as follows, either:
1. Treatment Period 1: Propagermanium capsule twice a day for 16 weeks
Treatment Period 2: Placebo capsule twice a day for 16 weeks.
OR
2. Treatment Period 1: Placebo capsule twice a day for 16 weeks
Treatment Period 2: Propagermanium capsule twice a day for 16 weeks.

This study will determine how safe and effective propagermanium is in the treatment of paients with FSGS by:
• monitoring symptoms that patients may experience while on the study
• measuring levels of protein in patients urine and kidney function during the course of the study.
• measuring the levels of propagermanium and irbesartan that enters into patients blood
• comparing the propagermanium result to patients' pre-study and placebo results
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 83774 0
Dr Simon Roger
Address 83774 0
Gosford Renal Research
Level 1/ 37 William Street,
Gosford New South Wales 2250
Country 83774 0
Australia
Phone 83774 0
+61 (0)2 4323 7977
Fax 83774 0
Email 83774 0
sdroger@bigpond.net.au
Contact person for public queries
Name 83775 0
Ms Alisha Smith
Address 83775 0
Dimerix Ltd, 425 Smith St, Fitzroy VIC 3065
Country 83775 0
Australia
Phone 83775 0
+61 1300 813 321
Fax 83775 0
Email 83775 0
alisha.smith@dimerix.com
Contact person for scientific queries
Name 83776 0
Dr Robert Shepherd
Address 83776 0
Dimerix Ltd, 425 Smith St, Fitzroy VIC 3065
Country 83776 0
Australia
Phone 83776 0
+61 1300 813 321
Fax 83776 0
Email 83776 0
robert.shepherd@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 other documents available
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary