Chronic Kidney Disease
Conditions
Keywords
radiocephalic, arteriovenous fistula, AVF, hemodialysis, PRT-201, vonapanitase, vascular access, kidney, renal, PATENCY-2, secondary patency, fistula abandonment, use for hemodialysis
Brief summary
This research study is designed to assess the safety and effectiveness of an experimental drug called vonapanitase (PRT-201) in patients both receiving or expecting to receive hemodialysis who have chronic kidney disease and who are undergoing surgery to create a new access point to their bloodstream for hemodialysis. Vonapanitase is a protein that has been shown in previous research studies to help keep vessels patent when applied to the outside surface of the blood vessels (arteries and veins) in patients who undergo surgery to create an arteriovenous fistula (AVF). The purpose of this study is to determine whether vonapanitase when applied to a limited segment of your blood vessel (about 2 inches) immediately after surgery is safe and improves the patency of your AVF.
Interventions
DRUGVonapanitase
DRUGPlacebo
Sponsors
Proteon Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
1. Age of at least 18 years. 2. Life expectancy of at least 6 months. 3. Diagnosis of CKD. 4. Planned creation of a new radiocephalic AVF (revision of an existing AVF is not eligible). 5. Ability to understand and comply with the requirements of the entire study and to communicate with the study team. 6. Written informed consent using a document that has been approved by the Institutional Review Board (IRB) or Independent Ethics Committee (IEC). 7. If female and of childbearing potential (premenopausal and not surgically sterile) must have a negative serum pregnancy test at the screening visit and be willing to use contraception from the time of the screening visit to 2 weeks following study drug administration. Acceptable methods of birth control include abstinence, barrier methods, hormones, or intra-uterine device.
Exclusion criteria
1. Malignancy or treatment for malignancy within the previous 12 months with the exception of the following cancers if they have been resected: localized basal cell or squamous cell skin cancer, or any cancer in situ. 2. Presence of any significant medical condition that might significantly confound the collection of safety and efficacy data in this study. 3. Previous treatment with vonapanitase (PRT-201). 4. Treatment with any investigational drug within the previous 30 days or investigational antibody therapy within the previous 90 days prior to signing informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Kaplan-Meier Estimate of Secondary AVF Patency | Median time from AVF creation to AVF abandonment (secondary patency), assessed up to 1 year. | Kaplan-Meier estimate of median time from AVF creation until AVF abandonment (secondary patency) |
| Number of Participants With AVF Use for Hemodialysis | Assessed at up to 12 Months | AVF use for hemodialysis is defined as the ability of the study AVF to be successfully cannulated and used for hemodialysis for a minimum of 90 days or at least 30 days prior to a patient's last visit, if hemodialysis has not been initiated at least 90 days prior to the patient's last visit. If AVF use is not defined as above, non-use of the AVF for hemodialysis is defined as an abandoned fistula prior to use; or if hemodialysis is recorded on 2 consecutive visits and there is no cannulation date or duration of use is less than 90 days. The patients who are not categorized as having use or non-use of the AVF have insufficient data to determine AVF use for hemodialysis and will be categorized as having indeterminate use. |
Countries
Canada, United States
Participant flow
Recruitment details
696 patients signed informed consent; 613 patients were randomized; 603 were treated
Pre-assignment details
Participants were excluded if they did not have a radiocephalic fistula created at the time of surgery
Participants by arm
| Arm | Count |
|---|---|
| Vonapanitase Vonapanitase administered at the time of radiocephalic fistula creation | 405 |
| Placebo Placebo administered at the time of radiocephalic fistula creation | 208 |
| Total | 613 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 17 | 14 |
| Overall Study | Lost to Follow-up | 13 | 6 |
| Overall Study | Randomized But Not Treated | 6 | 4 |
| Overall Study | Received a Kidney Transplant | 13 | 4 |
| Overall Study | Withdrawal by Subject | 7 | 5 |
Baseline characteristics
| Characteristic | Vonapanitase | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 128 Participants | 76 Participants | 204 Participants |
| Age, Categorical Between 18 and 65 years | 277 Participants | 132 Participants | 409 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 19 Participants | 10 Participants | 29 Participants |
| Race (NIH/OMB) Black or African American | 104 Participants | 45 Participants | 149 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 3 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 7 Participants | 3 Participants | 10 Participants |
| Race (NIH/OMB) White | 269 Participants | 149 Participants | 418 Participants |
| Region of Enrollment Canada | 41 participants | 18 participants | 59 participants |
| Region of Enrollment United States | 358 participants | 186 participants | 544 participants |
| Sex: Female, Male Female | 101 Participants | 46 Participants | 147 Participants |
| Sex: Female, Male Male | 304 Participants | 162 Participants | 466 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 17 / 399 | 14 / 204 |
| other Total, other adverse events | 247 / 399 | 135 / 204 |
| serious Total, serious adverse events | 48 / 399 | 30 / 204 |
Outcome results
Primary
Kaplan-Meier Estimate of Secondary AVF Patency
Kaplan-Meier estimate of median time from AVF creation until AVF abandonment (secondary patency)
Time frame: Median time from AVF creation to AVF abandonment (secondary patency), assessed up to 1 year.
Population: Full analysis set includes all 613 patients who were randomized
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Vonapanitase | Kaplan-Meier Estimate of Secondary AVF Patency | NA Days |
| Placebo | Kaplan-Meier Estimate of Secondary AVF Patency | NA Days |
p-value: 0.93295% CI: [0.67, 1.39]Log Rank
Primary
Number of Participants With AVF Use for Hemodialysis
AVF use for hemodialysis is defined as the ability of the study AVF to be successfully cannulated and used for hemodialysis for a minimum of 90 days or at least 30 days prior to a patient's last visit, if hemodialysis has not been initiated at least 90 days prior to the patient's last visit. If AVF use is not defined as above, non-use of the AVF for hemodialysis is defined as an abandoned fistula prior to use; or if hemodialysis is recorded on 2 consecutive visits and there is no cannulation date or duration of use is less than 90 days. The patients who are not categorized as having use or non-use of the AVF have insufficient data to determine AVF use for hemodialysis and will be categorized as having indeterminate use.
Time frame: Assessed at up to 12 Months
Population: Patients having use or non-use of their AVF. Patients with indeterminate use of their AVF were excluded.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Vonapanitase | Number of Participants With AVF Use for Hemodialysis | AVF Used | 209 Participants |
| Vonapanitase | Number of Participants With AVF Use for Hemodialysis | AVF Not Used | 91 Participants |
| Vonapanitase | Number of Participants With AVF Use for Hemodialysis | Indeterminant AVF Use | 105 Participants |
| Placebo | Number of Participants With AVF Use for Hemodialysis | AVF Used | 99 Participants |
| Placebo | Number of Participants With AVF Use for Hemodialysis | AVF Not Used | 53 Participants |
| Placebo | Number of Participants With AVF Use for Hemodialysis | Indeterminant AVF Use | 56 Participants |
p-value: 0.328Chi-squared