Multi-centre Study to Assess Safety, Tolerability and Renal Effects of APX-115 in Subjects with Type 2 Diabetes and Nephropathy

Phase 1

• Conditions: diabetic nephropathy; MedDRA version: 21.1Level: PTClassification code 10061835Term: Diabetic nephropathySystem Organ Class: 10038359 - Renal and urinary disorders; Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

• Registration Number: EUCTR2019-004155-37-CZ
• Lead Sponsor: Aptabio Therapeutics, Inc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-03-05
• Last Update Posted: 24 January 2022

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 140

Inclusion Criteria

1-Male/female subject, aged 18 to 80 years inclusive at the time of informed consent;
2-Clinical Diagnosis of type 2 diabetes;
3-18.5 kg/m² < BMI < 35 kg/m² ;
4-First morning void UACR between 200 and 3000 mg/g, inclusive (geometric mean of 2 FMV samples collected on 2 separate days during screening period;
5-30 mL/min/1.73m2 = eGFR = 90 mL/min/1.73m2 using CKD-EPI formula at screening;
6-Females of childbearing potential/Sexually active males with partner of childbearing potential: commitment to consistently and correctly use an acceptable method of birth control (oral, transdermal, systemic or implant contraception birth control, intrauterine devices, diaphragm or condoms) for the duration of the trial and for 4 months after the last study drug administration;
Females of non-childbearing potential: either surgically sterilized or at least 1 year postmenopausal (amenorrhoea duration at least 12 months);
7-Negative pregnancy test at screening and at randomization;
8-HbA1c = 10% at screening visit;
9-Subject who has been taking unchanged dosage of ACE inhibitor or ARB medication for at least 3 months prior to screening and is not anticipated to change its dosage during the course of the study. Subject who has not been taking ACE inhibitor or ARB medication may be screened and/or included in the study if he/she has a documented intolerance and/or side effects such as acute kidney injury to ACE inhibitor or ARB medication;
10-Subject who has been on stable anti-hyperglycemic treatment for at least 3 months prior to screening. For subject whose anti-hyperglycemic treatment includes SGLT2 inhibitor or DPP-4 inhibitor, dose change of these medications is not anticipated to occur during the course of the study;
11-Willing to be under dietary management for diabetes;
12-Willing to comply with all study procedures and availability for the duration of the study;
13-Capable of understanding the content of and able voluntarily to provide a signed and dated written informed consent form prior to any study procedures.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 140
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 140

Exclusion Criteria

1-Female subject who is pregnant or breastfeeding. Female subject should not be enrolled if she plans to become pregnant during the time of study participation;
2-History of type 1 diabetes mellitus or gestational diabetes;
3-Subject’s renal impairment and/or albuminuria is considered to be of origin other than Diabetic Kidney Disease;
4-History of renal transplant and/or plan to undergo a renal transplant during the course of the study;
5-History of acute kidney injury (AKI) or renal dialysis within 3 months prior to screening and/or plan to unergo a renal dialysis during the course of the study;
6-Subject with uncontrolled blood pressure
oDespite the use of three or more antihypertensive drugs, subject with uncontrolled hypertension with blood pressure greater than SBP 140 mmHg / DBP 90 mmHg
oSubject with clinically significant hypotension by the discretion of the investigator;
7-Subject taking two or more RAS blockers (ACE inhibitor, ARB, aldosterone antagonist);
8-Subject taking immunosuppressant including steroids, cyclosporine, or tacrolimus, or other immunosuppressant drugs;
9-Clinically significant abnormal laboratory findings at screening including :
oserum potassium > 5.5 mEq/L;
oALT > three times upper limit normal;
oAST > three times upper limit normal;
ototal bilirubin > three times upper limit normal;
oserum creatinine > 2 mg/dL;
10-History of drug or alcohol abuse within 1 year prior to screening;
11-History of any cardiovascular event (e.g. myocardial infarction, unstable angina within 6 months prior to screening) OR cardiovascular procedure planned during the clinical trial(e.g., revascularization procedure such as stent or bypass graft surgery);
12-Current or history of NYHA class IV heart failure;
13-Clinically significant ECG abnormalities on a 12-lead ECG at the screening visit or before randomization:
oQTcf = 430 ms for male and = 450 ms for female
onew clinically important arrhythmia or conduction disturbance;
14-Known significant liver disease (e.g. acute hepatitis, chronic active hepatitis)
15-Subject with active urinary tract infection or has not fully recovered before randomization;
16-History of malignancy within 5 years prior to screening (exceptions: squamous and basal cell carcinomas of the skin and carcinoma of the cervix in situ, or a malignancy that in the opinion of the investigator, with concurrence with the sponsor, is considered cured with minimal risk of recurrence);
17-Administration of any investigational product within 30 days or within 5 half-lives of the investigational product;
18-Diagnostic or interventional procedure requiring a contrast agent within 4 weeks before the screening visit or planned during the course of the study;
19-Major surgery within 28 days or not fully recovered surgery prior to randomization or major surgery planned during the next 6 months;
20-Positive HBs antigen or anti HCV antibody, or positive results for HIV 1 or 2 tests; positive for FANA (at a titre of greater than 1:80), ANCA, RF;
21-Other medical history which in the opinion of the investigator would make the subject unsuitable for participation in the study;
22-Subject who, in the judgment of the Investigator, is likely to be non-compliant or uncooperative during the study, or unable to cooperate because of a language problem, poor mental status.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the anti-albuminuric effects of APX-115 in subjects with type 2 diabetes and nephropathy.;Secondary Objective: • To evaluate the safety and tolerability of APX-115 in subjects with type 2 diabetes and nephropathy.<br>• To evaluate the mean change in eGFR between baseline and Week 12.<br>• To assess the pharmacodynamics of APX-115 by measurement of oxidative stress markers <br><br>Exploratory Objective:<br>• To evaluate the pharmacokinetics of APX-115 in subjects with type 2 diabetes and nephropathy<br>• To evaluate the thyroid function between baseline and week 12.;Primary end point(s): Mean change in UACR at Week 12 from baseline in APX-115 treatment group compared to placebo group.;Timepoint(s) of evaluation of this end point: week 12 and baseline

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): • Assessment of safety and tolerability : <br>o Adverse Events / Serious Adverse Events;<br>o Physical examinations;<br>o Vitals signs;<br>o Clinical laboratory measurements (chemistry, hematology, coagulation and urinalysis);<br>o ECG.<br>• Change in eGFR using CKD-EPI formula at Week 12 from baseline in APX-115 treatment group compared to placebo group.<br>• Assessment of the pharmacodynamics of APX-115 between baseline and Week 12:<br>o Change in plasma biomarkers: MCP-1 and 8-isoprostane <br>o Change in urinary biomarkers: 8-isoprostane, kidney injury molecule 1 (KIM-1), Cubilin, and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-OHdG)<br><br>Exploratory endpoint<br>• Plasma concentrations of APX-115 and other metabolites as appropriate<br>• Assessment of the thyroid function: free T4 and TSH <br>;Timepoint(s) of evaluation of this end point: each study visit