Safety and Effectiveness of Propagermanium in Diabetic Kidney Disease Participants Receiving Irbesartan

NCT03627715 | Completed Phase 2 DMC

• 2 other identifiers: DMX-200-203 AACTRN12618000982213p
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 13

Brief Summary

This study will be evaluating the safety and efficacy of propagermanium for the treatment of participants with DKD who are already taking irbesartan by:

• monitoring symptoms that participants may experience while on the study,
• measuring levels of protein in participant's urine and kidney function during the course of the study,
• measuring the levels of propagermanium and irbesartan that enters into participant's urine and blood, and
• comparing the propagermanium outcomes to participants' pre-study and placebo outcomes. Eligible participants will randomly be assigned to one of two arms to receive both the propagermanium and placebo in different orders as follows, either: Treatment Period 1 taking a propagermanium capsule twice a day for 12 weeks, followed by a six week washout period followed by Treatment Period 2 taking a placebo capsule twice a day for 12 weeks. OR Treatment Period 1 taking a placebo capsule twice a day for 12 weeks, followed by a six week washout period followed by Treatment Period 2 taking a propagermanium capsule twice a day for 12 weeks.

Conditions

Diabetic Kidney Disease

Outcome Measures

Primary Outcomes (1)

• The Change in Albumin/Creatinine Ratio with Adjunct use of Propagermanium Compared to Placebo in Participants with DKD who are Receiving Irbesartan

  Assessed by measuring albumin/creatinine ratio.

  Twelve weeks

Secondary Outcomes (3)

• The Effect of Treatment with Propagermanium Compared to Placebo on Measures of Estimated Glomerular Filtration Rate

  Twelve weeks

• The Number of Adverse Events with the Adjunct use of Propagermanium

  Twelve weeks

• The Effect of Treatment with Propagermanium on Measures of Proteinuria as measured by ACR

  Eleven 24-hour urine samples at week -2, week -1, week 6, week 11, week 12.

Study Arms (2)

Propagermanium then Placebo

EXPERIMENTAL

Propagermanium one capsule orally twice daily for 12 weeks. Compliance will be measured by drug accountability and completion of a participant diary. Participants will receive 12 weeks propagermanium and 12 weeks placebo separated by a 6 week washout period.

Drug: Propagermanium; Drug: Placebo

Placebo then Propagermanium

EXPERIMENTAL

Propagermanium one capsule orally twice daily for 12 weeks. Compliance will be measured by drug accountability and completion of a participant diary. Participants will receive 12 weeks placebo and 12 weeks propagermanium separated by a 6 week washout period.

Drug: Propagermanium; Drug: Placebo

Interventions

Propagermanium DRUG

Immediate release capsule

Also known as: PPG, repagermanium, DMX-200

Placebo then Propagermanium; Propagermanium then Placebo

Placebo DRUG

Placebo capsule

Placebo then Propagermanium; Propagermanium then Placebo

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18 to 90 (inclusive) at screening;
• A diagnosis of type 2 diabetes mellitus;
• Baseline glycated haemoglobin (HbA1c) ≤ 12%;
• Fasting plasma glucose \< 21 mmol/L;
• 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;
• Patients can be on stable doses of angiotensin converting enzyme inhibitors, aldosterone inhibitors, and/or sodium-glucose co-transporter-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;
• Mean of two albumin creatinine ratio (ACR) values (screening and baseline) of more than or equal to 265 to 4,425 mg/g (30-500 mg/mmol) and within 30% of the screening value at the baseline assessment;
• Estimated glomerular filtration rate more than or equal to 25-90 mL/min/1.73 m\^2 using chronic kidney disease epidemiology collaboration (CKD-EPI) formula at screening;
• 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 one week after the second value
• A female patient is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 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;
• 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;
• Have given written informed consent prior to any study procedures being performed.

You may not qualify if:

• A history of type 1 diabetes mellitus;
• Current known non-diabetic renal disease. Patients with a history of other resolved renal diseases must be approved by the Sponsor;
• A prior organ or stem cell transplant;
• A major adverse cardiac event within 6 months before screening;
• Patients receiving immunosuppressive medications including patients receiving \> 5 mg prednisone;
• Rapid estimated glomerular filtration rate decline with renal replacement likely during study
• 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;
• Jaundice, active hepatitis, or known hepatobiliary disease (except asymptomatic cholelithiasis);
• Alanine aminotransferase and/or aspartate aminotransferase more than two times the upper limit of normal at screening;
• 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;
• Positive screening assessment for viral hepatitis B surface antigen or hepatitis C virus (HCV) antibody AND positive HCV ribonucleic acid or human immunodeficiency virus (HIV);
• Seated blood pressure of more than or equal to 160/100 mmHg at screening;
• Body mass index more than or equal to 42 kg/m\^2 at screening;
• Past hospitalisation for a major depressive episode;
• Is breast feeding or pregnant;

Sponsors & Collaborators

• Dimerix Bioscience Pty Ltd: lead
• Iqvia Pty Ltd: collaborator

Study Sites (13)

Renal Research

Gosford, New South Wales, Australia

Location

Liverpool Hospital

Liverpool, New South Wales, 2170, Australia

Location

Royal North Shore Hospital

St Leonards, New South Wales, 2065, Australia

Location

Westmead Hospital

Westmead, New South Wales, 2145, Australia

Location

Sunshine Coast University Hospital

Birtinya, Queensland, 4575, Australia

Location

Princess Alexandra Hospital

Woolloongabba, Queensland, 4102, Australia

Location

Boxhill Hospital

Box Hill, Victoria, 3128, Australia

Location

Austin Hospital

Heidelberg, Victoria, 3084, Australia

Location

Sunshine Hospital

Melbourne, Victoria, 3021, Australia

Location

Melbourne Renal Research Group

Melbourne, Victoria, Australia

Location

Royal Melbourne Hospital

Melbourne, Victoria, Australia

Location

St Vincents Hospital

Melbourne, Victoria, Australia

Location

Epworth Hospital

Richmond, Victoria, 3121, Australia

Location

MeSH Terms

Conditions

Diabetic Nephropathies

Interventions

propagermanium

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases

Study Officials

• Simon Roger, MD

  Renal Research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Double-blind, Randomised, Placebo-Controlled, Crossover Study

Study Record Dates

• First Submitted: August 7, 2018
• First Posted: August 13, 2018
• Study Start: November 6, 2018
• Primary Completion: July 23, 2020
• Study Completion: August 18, 2020
• Last Updated: July 29, 2022

Record last verified: 2020-02

Locations

AU (13)