diabetic kidney disease (DKD)

Primary objective: To detect the existence of an overall dose-response relationship with gevokizumab (3mg, 10 mg, 30 mg, or 60 mg) SC, on the measured glomerular filtration rate (mGFR) in patients with type 2 diabetes and diabetic kidney disease (DKD) on top of standard of care, after 52 weeks of treatment.

S78989

Gevokizumab

Injection

3、10、30 、60mg /mL/vial

Efficacy measurements
Primary efficacy endpoint:
- GFR measured by plasma clearance of iohexol.
Secondary efficacy endpoints:
- Estimated GFR (eGFR) calculated with creatinine and/or cystatin C-based equations using the
Modification Diet Disease equation (MDRD) and the CKD-EPI creatinine-cystatin C equation (2012).
- Albuminuria, estimated by the first morning void albumin to creatinine ratio (ACR)
- Number of patients with 15% reduction in eGFR per year
Safety measurements
Safety endpoints:
- Adverse events
- Vital signs including blood pressure (systolic/ diastolic), pulse rate, weight, body temperature,
- Laboratory parameters (hematology panel, biochemistry panel, and urinalysis),
- Standard 12-lead Electrocardiogram (ECG),
- Ophthalmological assessment.

Main selection/inclusion criteria
- Known type 2 diabetes with a diagnosis made at age ≥30 years or later and ≥8 years prior to selection.
- Estimated glomerular filtration rate (eGFR) calculated using the Modification of Diet in Renal Disease
(MDRD) equation within the 20-60 mL/min/1.73 m2 range.
- Urinary albumin-to-creatinine ratio (UACR) >300 mg/g.
- HbA1c <10%, with at least one glucose-lowering therapy (insulin included) for at least six months prior
to selection. (Dapagliflozin or any SGLT 2 inhibitors are prohibited).
- Systolic blood pressure ≤160 mmHg and diastolic blood pressure ≤100 mmHg.
- Treatment by angiotensin converting enzyme (ACE) inhibitor or by angiotensin-II receptor blocker
(ARB) unless medically justified and documented; and at a stable dose for at least 6 weeks prior to
selection visit.
- Patients must agree to use highly effective methods of birth control. Highly effective methods of birth
control refer to those which result in a low failure rate (i.e. less than 1% per year). These highly effective
methods of birth control will be defined according to local regulation. For women of childbearing
potential, negative serum and urine pregnancy.
- Patients with no evidence of active or latent tuberculosis assessed by detailed medical history and
appropriate screening test including at least :
1) baseline chest X-Ray within the 12 weeks prior to selection,
and
2) baseline IGRA test with negative results.
- Informed consent obtained prior any study-specific procedures.

Main non selection/ exclusion criteria
- Fever or infection requiring treatment with systemic anti-infectives within 3 weeks prior to selection
- Major general surgery within 3 months prior to selection, or anticipated during the study period.
- NYHA class III or IV congestive heart failure
- History of acute coronary syndrome, stroke or transient ischemic attack (TIA) within 3 months prior to
selection visit
- History or symptoms of demyelinating disease
- History of malignancy within 5 years prior selection other than carcinoma in situ of the cervix or
adequately treated, non-metastatic squamous or basal cell carcinoma of the skin
- History of severe allergic or anaphylactic reaction to monoclonal antibodies
- Diagnostic or interventional procedure requiring a contrast agent within 30 days prior to selection
- Treatment with biological agents within 6 weeks (for anti TNF α ie: pentoxifylline, anti-IL1) or within 3
months prior to inclusion visit for (but not restrictive to) interferon, infliximab, daclizumab, etanercept,
anakinra, canakinumab or adalimumab, either marketed or investigational medicinal products),(other than
antivitreal anti VEGF which are allowed)
- Any immunosuppressive therapy within 3 months prior to inclusion,
- Any systemic corticosteroids (>20 mg/day of prednisolone or equivalent) within 1 month prior to
inclusion,
- Any live (attenuated) vaccine within 3 months prior to inclusion; recombinant or killed virus vaccines are
permitted.
- Prior treatment with pentoxifylline within 3 months prior to inclusion,
- Prior treatment with gevokizumab.
- Known primary immunodeficiency, known seropositivity for human immunodeficiency virus (HIV),
hepatitis C, or hepatitis B.