To Evaluate the Effect and Safety of Telitacicept and Standard Treatment for 6months in IgA Nephropathy, Single Center, Randomized, Open Label, Comparative Study
Trial Snapshot
- Phase
- Phase 3
- Status
- Active, not recruiting
- Enrollment
- 150
- Locations
- 1
- Primary Endpoint
- Complete remission of proteinuria
Study Overview
Brief Summary
The purpose of this clinical study is to evaluate the efficacy and safety of that test group was administered with Telitacicept in patients with IgA nephropathy. The control group will be observed for up to 6months without administration of Telitacicept.
This Single center, Randomized, Open Label, Comparative study will evaluate the effect and safety of and Standard treatment for 6months in IgA Nephropathy.
Detailed Description
IgA nephropathy is the most common primary glomerulonephritis worldwide. Immune complexes, composed of galactose-deficient IgA1 and Gd-IgA1 autoantibodies, are deposited in the mesangial area of the glomeruli where they induce complement-mediated inflammation. This may result in the reduced kidney function, which can progress to end-stage kidney disease. Treatment options are very limited. It has been reported that for urinary protein excretion that is persistently more than 1g/24h and eGFR>50ml/min/1.73m2 in IgA nephropathy, the KDIGO guidelines suggest a 6-month course of glucocorticoids. Many studies further showed that 6-month course of glucocorticoids with higher side effects and leading to discontinue of glucocorticoids course before the beneficial effect of 6months course. Currently monoclonal antibodies, that may affect the main axis of pathogenesis of IgA nephropathy and biological therapy such as Telitacicept, provides a new treatment option and altering or depletion or modulation of Gd-IgA1 producing B cells and plasma cells. At present, Telitacicept are used for clinical treatment in IgA nephropathy patient inside China, but still clear data on safety and effect, and patient's complete remission, repeated relapse data are unclear. This study is a Single center, Randomized, Open Label, Comparative study. In the study, around 60-100 patients with IgA nephropathy will be enrolled, and they will be treated with Telitacicept for 6 months on the basis of conventional treatment.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Age 18~75 years, regardless of gender.
- •Clinical evaluation and renal biopsy diagnostic for IgA nephropathy.
- •Average urinary protein excretion of 0.3~3.5g/24h on two successive examinations.
- •Urine Protein to Creatinine Ratio (UPCR) >= 0.75 and <= 6 milligram per milligram (mg/mg) during screening.
- •Stable and optimal dose of Angiotensin converting enzyme (ACE) inhibitor and/or angiotensin II receptor blockers (ARB) at least 8 weeks prior to screening.
- •eGFR≥30 ml/min/1.73m
- •Willingness to sign an informed consent.
Exclusion Criteria
- •• Secondary IgA nephropathy such as systemic lupus erythematosus, Henoch-Schonlein purpuric nephritis and hepatitis B-associated nephritis, etc.
- •IgA nephropathy with significant glomerulosclerosis or cortical scarring.
- •Failure to meet estimated glomerular filtration rate (eGFR) and biopsy requirement criteria.
- •Rapidly progressive nephritic syndrome.
- •Acute renal failure, including rapidly progressive IgA nephropathy.
- •Current or recent (within 30 days) exposure to high-dose of steroids or immunosuppressive therapy (CTX、MMF、CsA、FK506).
- •Cirrhosis, chronic active liver disease, and serious liver function damage.
- •History of significant gastrointestinal disorders (e.g. severe chronic diarrhea or active peptic ulcer disease).
- •Any Active systemic infection or history of serious infection within one month.
- •Other major organ system disease (e.g. serious cardiovascular diseases including congestive heart failure, chronic obstructive pulmonary disease, asthma requiring oral steroid treatment or central nervous system diseases).
- •Active tuberculosis or untreated latent TB infection.
- •Malignant hypertension that is difficult to be controlled by oral drugs.
- •Known allergy, contraindication, or intolerance to the steroids.
- •Pregnancy or breast feeding at the time of entry or unwillingness to comply with measures for contraception.
- •Malignant tumors.
- •Excessive drinking or drug abuse.
- •Mental aberrations.
- •Any condition, including any uncontrolled disease state other than IgA nephropathy.
Arms & Interventions
Target Therapy Group(TTG)
Standard Supportive Care plus Telitacicept injected Subcutaneously 160mg/time, once a week for a total of 24 weeks Target based Drug: Telitacicept 160mg once a week for 24 weeks Other Name: RC18 Drug: Standard Supportive Care plus Low dosage of Corticosteroid(≤0.5mg/kg/d) without immunosuppressants Other Name: Prednisolone / Methylprednisolone
Intervention: Telitacicept 160mg (Drug)
Corticosteroid Therapy Group (CTG)
Standard Supportive Care plus Corticosteroid Drug: Standard Supportive Care plus Corticosteroid(≤1mg/kg/d) without immunosuppressants Other Name: Prednisolone / Methylprednisolone
Intervention: Corticosteroid (Drug)
Supportive Care Group (SCG)
Standard Supportive Care Drug: ACE Inhibitor (Treatment for proteinuria suppression and blood pressure regulation) - 2-3months before randomization Drug: ARB Inhibitor (Treatment for proteinuria suppression and blood pressure regulation) - 2-3months before randomization
Intervention: ACE Inhibitor or Angiotensin receptor antagonist (Drug)
Outcomes
Primary Outcomes
Complete remission of proteinuria
Time Frame: Baseline/3months/6months
Proteinuria\<0.3g/24h
Partial remission of proteinuria
Time Frame: Baseline/3months/6months
Proteinuria decline\>50%
Change from baseline to 6months in 24 Hours Urine Protein in g/24hrs
Time Frame: Baseline/3months/6months
Compare the Baseline 24 Hours Urine Protein to 6month
Change from baseline to 6months in eGFR
Time Frame: Baseline/3months/6months
Compare the baseline eGFR to 6months
Secondary Outcomes
- Deterioration of renal function(Baseline/3months/6months)
- Change From Baseline Levels in Serum Immunoglobulin A (IgA) Levels in Serum Immunoglobulin G (IgG) Levels in Serum Immunoglobulin M (IgM)(Baseline/ 3months/6months)
- Change From Baseline in Serum Complement C3 and C4 Levels(Baseline/3months/6months)
- Percentage of Participants With Clinical Significant Abnormalities in Laboratory Assessments, including Blood Pressure(Baseline/3months/6months)
- Number of Participants With a Treatment-emergent Adverse Event (TEAE)(Baseline/3months/6months)
- Number of Participants Who Experienced a Serious Adverse Event (SAE)(Baseline/3months/6months)
Investigators
Dong Sun
Head of Nephrology Department
The Affiliated Hospital of Xuzhou Medical University