Chronic Kidney Disease, IgA Nephropathy
Conditions
Keywords
Chronic kidney disease, IgA nephropathy, Velcade®, Proteinuria, Bortezomib, Proteasome inhibitor
Brief summary
The primary objective of this study is to investigate the ability of Velcade® (bortezomib) to induce complete or partial remission in patients with severe IgA nephropathy. The secondary objectives are to assess clinical outcomes relating to safety and efficacy, such as infection, malignancy, preservation of renal function, partial responders, relapse rate, and to study mechanistic assays to predict remission.
Detailed description
This exploratory single center, open-label, single treatment group assignment, safety and efficacy study will enroll 15 patients with severe IgA nephropathy. Subjects will receive 1 cycle of Velcade® to induce clinical remission. Follow-up visits will occur monthly for a year. For this pilot study, the proportion of patients with clinical remission or partial response will be analyzed.
Interventions
Velcade® at 1.3 mg/m2, on days 1, 4, 8 and 11 (=1 cycle).
Sponsors
Weill Medical College of Cornell University
The Rogosin Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female, 18 years of age or older. 2. Must have IgA nephropathy documented by kidney biopsy. 3. Must have greater than 1gm of proteinuria a day. 4. Must be on a stable dose of Angiotensin Converting Enzyme Inhibitor (ACEI) and/or Angiotensin Receptor Blocking agent (ARB) for at least 4 weeks prior to screening.
Exclusion criteria
1. Low platelet count and neutrophil count within certain limits defined for enrollment. 2. Underlying peripheral neuropathy. 3. Having cardiac problems, such as myocardial infarction, heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. 4. Allergic to VELCADE®, boron or mannitol. 5. Female subjects who are pregnant or breast-feeding. 6. Recent use of investigational drug within 14 days before enrollment. 7. Having serious medical conditions and infections (including HIV,or hepatitis B or C) or psychiatric illness likely to interfere with participation in the study. 8. Diagnosed or treated for cancer within 3 years of participation in the study, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, and in situ malignancy, or low-risk prostate cancer after curative therapy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proteinuria | Baseline and 1 year | Quantification of urinary protein will be made after treatment by measuring 24 hr urine protein. |
| Number of Participants With Complete Remission, Partial Response, or no Response. | 1 year | Complete remission was defined as daily proteinuria of less than 300mg measured by 24 hr urine collection. Partial response was defined as any reduction in daily proteinuria from baseline as measure by 24 hr urine collection. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum Creatinine | Baseline and 1 year | Preservation of renal function will be assessed. |
| Number of Participants With Abnormal Lab Values or Infections Related to Exposure to Study Medication. | 1 year | Complete blood count will be checked at regular intervals to monitor for anemia; liver panel; serum immunoglobulin profile will also be followed. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Velcade® Therapy Bortezomib (Velcade®): Velcade® at 1.3 mg/m2, on days 1, 4, 8 and 11 (=1 cycle). | 8 |
| Total | 8 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Proteinuria improved prior to enrollment | 1 |
| Overall Study | Screen failure | 1 |
Baseline characteristics
| Characteristic | Velcade® Therapy |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants |
| Age, Continuous | 35 years STANDARD_DEVIATION 12 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 4 Participants |
| Region of Enrollment United States | 8 participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 8 |
| other Total, other adverse events | 1 / 8 |
| serious Total, serious adverse events | 0 / 8 |
Outcome results
Primary
Number of Participants With Complete Remission, Partial Response, or no Response.
Complete remission was defined as daily proteinuria of less than 300mg measured by 24 hr urine collection. Partial response was defined as any reduction in daily proteinuria from baseline as measure by 24 hr urine collection.
Time frame: 1 year
Population: 1 participant was lost to followup.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Velcade® Therapy | Number of Participants With Complete Remission, Partial Response, or no Response. | Complete Remission | 3 Participants |
| Velcade® Therapy | Number of Participants With Complete Remission, Partial Response, or no Response. | Partial Response | 1 Participants |
| Velcade® Therapy | Number of Participants With Complete Remission, Partial Response, or no Response. | No Response | 3 Participants |
Primary
Proteinuria
Quantification of urinary protein will be made after treatment by measuring 24 hr urine protein.
Time frame: Baseline and 1 year
Population: 1 participant was lost to followup.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Velcade® Therapy | Proteinuria | Baseline | 2.52 grams per 24 hrs |
| Velcade® Therapy | Proteinuria | 1 year | 1.43 grams per 24 hrs |
Secondary
Number of Participants With Abnormal Lab Values or Infections Related to Exposure to Study Medication.
Complete blood count will be checked at regular intervals to monitor for anemia; liver panel; serum immunoglobulin profile will also be followed.
Time frame: 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Velcade® Therapy | Number of Participants With Abnormal Lab Values or Infections Related to Exposure to Study Medication. | 1 Participants |
Secondary
Serum Creatinine
Preservation of renal function will be assessed.
Time frame: Baseline and 1 year
Population: 1 participant lost to followup.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Velcade® Therapy | Serum Creatinine | Baseline | 1.35 milligram per deciliter |
| Velcade® Therapy | Serum Creatinine | 1 year | 1.52 milligram per deciliter |