Safety, Tolerability and Efficacy of Nidufexor in Patients With Diabetic Nephropathy

Novartis

Status and phase: Completed; Phase 2

Conditions: Diabetic Nephropathy

Treatments: Drug: Nidufexor; Drug: Standard of Care (SoC); Other: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT03804879

CLMB763X2202

2018-002491-40 (EudraCT Number)

Details and patient eligibility

About

Nidufexor addresses fibrosis, oxidative stress, inflammation and cell death, and therefore has the potential to improve the management of diabetic kidney disease when added to the standard of care (SoC) (angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB)).

This non-confirmatory Phase 2 study was designed to determine the safety, tolerability, efficacy, pharmacokinetics and pharmacodynamics of nidufexor in combination with ACEI or ARB at a dose level that is SoC as judged by the study doctor in patients with type 2 diabetes and nephropathy.

Full description

This was a non-confirmatory, multicenter, patient- and investigator-blinded, randomized, and placebo-controlled, proof-of concept trial assessing nidufexor vs. placebo in patients receiving standard of care (optimal tolerated doses of ARB or ACEI) for diabetic nephropathy due to type 2 diabetes.

The study consisted of three distinct study periods:

Screening (Day -30 to Day-1): lasted up to a maximum of 30 days and comprised a screening / baseline assessment. This visit was used to confirm that the study inclusion and exclusion criteria were met and served as baseline assessment prior to randomization. Participant randomization occurred prior to day 1 as soon as participant eligibility was confirmed.

Treatment period (Day 1-168): Participants were randomized in a 1:1 ratio to receive nidufexor 50 mg or placebo once daily for 24 weeks. Nidufexor and placebo were given in addition to SoC (optimal tolerated doses of ARB or ACEI).

End of Study (EOS) and Safety follow-up (Day 169 to Day 197): Study assessments were performed until the EOS visit (Day 169). Post Study Safety Contact occurred approximately 28 days after discontinuing study treatment until day 197.

Enrollment: 83 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Male/female patients, 18-75 years
• Written informed consent
• Diagnosis of Type 2 diabetes mellitus, with diagnosis made at least 6 months prior to screening
• Diabetic nephropathy as evidenced by Urine albumin-Cr ratio (UACR) ≥300 mg/g Cr at screening while receiving a dose of angiotensin converting enzyme inhibitor or angiotensin receptor blocker that is the standard of care as judged by the study doctor.

Exclusion criteria

• History of type 1 diabetes mellitus
• Severe renal impairment manifesting as serum creatinine eGFR < 30 mL/min/1.73 m^2 at screening
• Pregnant or nursing (lactating) women
• Women of child-bearing potential, unless they are using basic methods of contraception during dosing of study treatment
• Uncontrolled diabetes mellitus at screening
• History or current diagnosis of ECG abnormalities prior to first study dose
• History of kidney disease other than diabetic nephropathy at screening
• Uncontrolled hypertension at screening
• Use of prohibited medications, including but not limited to GLP-1 agonists and SGLT2 inhibitors.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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83 participants in 2 patient groups, including a placebo group

LMB763

Experimental group

Description:

50 mg LMB763 (two LMB763 25 mg capsules) were orally administered once daily for 24 weeks in addition to SoC.

Treatment:

Drug: Standard of Care (SoC)

Drug: Nidufexor

Placebo

Placebo Comparator group

Description:

Placebo was orally administered once daily for 24 weeks in addition to SoC.

Treatment:

Drug: Standard of Care (SoC)

Other: Placebo