Chronic Kidney Disease
Conditions
Keywords
radiocephalic, arteriovenous fistula, AVF, hemodialysis, PRT-201, vascular access, kidney, renal, vonapanitase, PATENCY-1
Brief summary
This research study is designed to assess the safety and effectiveness of an experimental drug called PRT-201 in patients both receiving or expecting to receive dialysis who have chronic kidney disease and who are undergoing surgery to create a new access point to their bloodstream for hemodialysis. PRT-201 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 PRT-201 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
DRUGPRT-201
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 Chronic Kidney Disease (CKD). 4. Planned creation of a new radiocephalic arteriovenous fistula (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). 7. If female and of childbearing potential (premenopausal and not surgically sterile) must have a negative serum pregnancy test at the screening visit (Visit 1) 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 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 |
|---|---|---|
| Time to AVF Primary Unassisted Patency | Days from AVF creation until the first occurrence of either access thrombosis or procedure to restore or maintain patency, assessed up to 1 year | Primary unassisted patency defined as the time from AVF creation until the first occurrence of either access thrombosis or procedure to restore or maintain patency. |
| Kaplan-Meier Estimate of Secondary AVF Patency | Median time from AVF creation until AVF abandonment (secondary patency), assessed up to 1 year | Kaplan-Meier Estimate of median time from AVF creation until AVF abandonment (secondary patency) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Unassisted AVF Maturation by Ultrasound | Assessed 3 months after AVF creation | AVF maturation is defined as average cephalic vein lumen diameter \>= 4 mm and an outflow vein volume blood flow \>= 500 mL/min by ultrasound without prior primary unassisted patency loss. |
| Number of Participants With Unassisted AVF Use for Hemodialysis | Assessed at 12 months | Unassisted AVF use for hemodialysis is defined as continuous use of the AVF for hemodialysis without prior primary unassisted patency loss. Use of the AVF 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 was not initiated at least 90 days prior to the last visit. 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 by the rules described above have insufficient data to determine use for hemodialysis and will be categorized as having indeterminate use. |
Countries
United States
Participant flow
Recruitment details
349 patients signed informed consent; 313 patients were randomized; 311 were treated
Pre-assignment details
Participants were excluded from participation if they did not have a radiocephalic AVF created at the time of surgery.
Participants by arm
| Arm | Count |
|---|---|
| Vonapanitase Single application administered over 10 minutes at the time of fistula creation. | 209 |
| Placebo Single application administered over 10 minutes at the time of fistula creation. | 102 |
| Total | 311 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 6 | 3 |
| Overall Study | Lost to Follow-up | 12 | 8 |
| Overall Study | received a kidney transplant | 5 | 0 |
| Overall Study | Withdrawal by Subject | 7 | 3 |
Baseline characteristics
| Characteristic | Vonapanitase | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 66 Participants | 31 Participants | 97 Participants |
| Age, Categorical Between 18 and 65 years | 143 Participants | 71 Participants | 214 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 29 Participants | 19 Participants | 48 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 180 Participants | 83 Participants | 263 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 5 Participants | 11 Participants |
| Race (NIH/OMB) Black or African American | 55 Participants | 19 Participants | 74 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 6 Participants | 7 Participants | 13 Participants |
| Race (NIH/OMB) White | 138 Participants | 71 Participants | 209 Participants |
| Region of Enrollment United States | 209 participants | 102 participants | 311 participants |
| Sex: Female, Male Female | 36 Participants | 26 Participants | 62 Participants |
| Sex: Female, Male Male | 173 Participants | 76 Participants | 249 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 7 / 209 | 4 / 102 |
| other Total, other adverse events | 149 / 209 | 84 / 102 |
| serious Total, serious adverse events | 29 / 209 | 15 / 102 |
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 until AVF abandonment (secondary patency), assessed up to 1 year
Population: Full analysis set included all 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: 0.04895% CI: [0.43, 1]Log Rank
Primary
Time to AVF Primary Unassisted Patency
Primary unassisted patency defined as the time from AVF creation until the first occurrence of either access thrombosis or procedure to restore or maintain patency.
Time frame: Days from AVF creation until the first occurrence of either access thrombosis or procedure to restore or maintain patency, assessed up to 1 year
Population: Full analysis set includes any patient who was randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Vonapanitase | Time to AVF Primary Unassisted Patency | 214 Days |
| Placebo | Time to AVF Primary Unassisted Patency | 171 Days |
p-value: 0.25495% CI: [0.61, 1.14]Log Rank
Other Pre-specified
Number of Participants With Unassisted AVF Maturation by Ultrasound
AVF maturation is defined as average cephalic vein lumen diameter \>= 4 mm and an outflow vein volume blood flow \>= 500 mL/min by ultrasound without prior primary unassisted patency loss.
Time frame: Assessed 3 months after AVF creation
Population: Full analysis set includes any patient who was randomized
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Vonapanitase | Number of Participants With Unassisted AVF Maturation by Ultrasound | With Unassisted AVF Maturation | 132 Participants |
| Vonapanitase | Number of Participants With Unassisted AVF Maturation by Ultrasound | Without Unassisted AVF Maturation | 78 Participants |
| Placebo | Number of Participants With Unassisted AVF Maturation by Ultrasound | With Unassisted AVF Maturation | 55 Participants |
| Placebo | Number of Participants With Unassisted AVF Maturation by Ultrasound | Without Unassisted AVF Maturation | 48 Participants |
p-value: 0.109Chi-squared
Other Pre-specified
Number of Participants With Unassisted AVF Use for Hemodialysis
Unassisted AVF use for hemodialysis is defined as continuous use of the AVF for hemodialysis without prior primary unassisted patency loss. Use of the AVF 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 was not initiated at least 90 days prior to the last visit. 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 by the rules described above have insufficient data to determine use for hemodialysis and will be categorized as having indeterminate use.
Time frame: Assessed at 12 months
Population: Patients with unassisted use or non-use of their AVF for hemodialysis. Patients with indeterminate use of their AVF were excluded.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Vonapanitase | Number of Participants With Unassisted AVF Use for Hemodialysis | New AVF Used Unassisted | 62 Participants |
| Vonapanitase | Number of Participants With Unassisted AVF Use for Hemodialysis | New AVF Not Used or Assisted Use | 96 Participants |
| Placebo | Number of Participants With Unassisted AVF Use for Hemodialysis | New AVF Used Unassisted | 18 Participants |
| Placebo | Number of Participants With Unassisted AVF Use for Hemodialysis | New AVF Not Used or Assisted Use | 54 Participants |
p-value: 0.035Chi-squared