A Study of PRT-201 Administered Immediately After Radiocephalic Arteriovenous Fistula(AVF) Creation in Patients With Chronic Kidney Disease (CKD) (PATENCY-1)

• Sponsor: Proteon Therapeutics (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02110901
• Collaborator: (none)
• Enrollment: 349
• Locations: 35
• Arms: 2
• Actual Duration (Months): 53
• Patients Per Site: 10
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Kidney Disease	Drug: PRT-201; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 349 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Multicenter, Double-Blind, Placebo-Controlled Study of PRT-201 Administered Immediately After Radiocephalic Arteriovenous Fistula Creation in Patients With Chronic Kidney Disease
• Actual Study Start Date: Jul 1, 2014
• Actual Primary Completion Date: Dec 1, 2016
• Actual Study Completion Date: Dec 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: PRT-201 PRT-201 administered at the time of radiocephalic fistula creation	Drug: PRT-201; Other Names: vonapanitase
Placebo Comparator: Placebo Placebo administered at the time of radiocephalic fistula creation. The placebo is identical in appearance and composition to PRT-201 but lacks the active ingredient.	Drug: Placebo

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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 Outcome Measures

1. 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.

2. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 100 Years
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
2	AKDHC Medical Research Services , LLC	Phoenix	Arizona	United States	85012
3	AKDHC Medical Research Services, LLc	Tucson	Arizona	United States	85719
4	Alliance Research Center	Laguna Hills	California	United States	92653
5	VA Medical Center Long Beach	Long Beach	California	United States	90822
6	Keck University Hospital at USC	Los Angeles	California	United States	90033
7	Kaiser Permanente Medical Center	San Diego	California	United States	92120
8	California Institute of Renal Research	San Diego	California	United States	92123
9	UCSF Division of Vascular & Endovascular Surgery	San Francisco	California	United States	94143
10	Rush Medical Center	Chicago	Illinois	United States	60612
11	Renal Care Associates	Peoria	Illinois	United States	61603
12	Lutheran Hospital Network of Indiana	Fort Wayne	Indiana	United States	46804
13	University of Iowa Hospitals and Clinics	Iowa City	Iowa	United States	52242
14	University of Louisville	Louisville	Kentucky	United States	40202
15	Tulane University	New Orleans	Louisiana	United States	70112
16	Louisiana State University Health Sciences Center	Shreveport	Louisiana	United States	71130
17	Maine Medical Center	Portland	Maine	United States	04102
18	University of Maryland	Baltimore	Maryland	United States	21201
19	University of Maryland Shore Medical Center at Easton	Easton	Maryland	United States	21601
20	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
21	Brigham and Women's Hospital	Boston	Massachusetts	United States	02482
22	University of Massachusetts Medical Center	Worcester	Massachusetts	United States	01655
23	Mount Sinai Medical Center	New York	New York	United States	10029
24	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina	United States	27599
25	Duke University	Durham	North Carolina	United States	27710
26	W.G. Hefner VA Medical Center	Salisbury	North Carolina	United States	28144
27	Wake Forest	Winston-Salem	North Carolina	United States	27157
28	University of Cincinnati Medical Center	Cincinnati	Ohio	United States	45267
29	University of Cincinnati	Cincinnati	Ohio	United States	45267
30	Ohio State University	Columbus	Ohio	United States	43210
31	The University of Oklahoma College of Medicine	Tulsa	Oklahoma	United States	74104
32	Lehigh Valley Health Network	Allentown	Pennsylvania	United States	18103
33	VA Pittsburg Healthcare System	Pittsburgh	Pennsylvania	United States	15240
34	The Methodist Hospital	Houston	Texas	United States	77030
35	Lake Washington Vascular Center	Bellevue	Washington	United States	98004

Sponsors and Collaborators

• Proteon Therapeutics

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Proteon Therapeutics
• ClinicalTrials.gov Identifier: NCT02110901
• Other Study ID Numbers: PRT-201-310
• First Posted: Apr 10, 2014
• Last Update Posted: Jul 9, 2019
• Last Verified: Jun 1, 2019

• Keywords provided by Proteon Therapeutics: radiocephalic; arteriovenous fistula; AVF; hemodialysis; PRT-201; vascular access; kidney; renal; vonapanitase; PATENCY-1
• Additional relevant MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Arteriovenous Fistula; Fistula

Study Results

Participant Flow

Recruitment Details	349 patients signed informed consent; 313 patients were randomized; 311 were treated
Pre-assignment Detail	Participants were excluded from participation if they did not have a radiocephalic AVF created at the time of surgery.

Arm/Group Title	Vonapanitase	Placebo
Arm/Group Description	Vonapanitase administered at the time of radiocephalic fistula creation	Placebo administered at the time of radiocephalic fistula creation
Period Title: Overall Study
STARTED	209	102
COMPLETED	179	88
NOT COMPLETED	30	14

Baseline Characteristics

Arm/Group Title	Vonapanitase	Placebo	Total
Arm/Group Description	Single application administered over 10 minutes at the time of fistula creation.	Single application administered over 10 minutes at the time of fistula creation.	Total of all reporting groups
Overall Participants	209	102	311
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	143 68.4%	71 69.6%	214 68.8%
>=65 years	66 31.6%	31 30.4%	97 31.2%
Sex: Female, Male (Count of Participants)
Female	36 17.2%	26 25.5%	62 19.9%
Male	173 82.8%	76 74.5%	249 80.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	29 13.9%	19 18.6%	48 15.4%
Not Hispanic or Latino	180 86.1%	83 81.4%	263 84.6%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	2 1%	0 0%	2 0.6%
Asian	6 2.9%	5 4.9%	11 3.5%
Native Hawaiian or Other Pacific Islander	2 1%	0 0%	2 0.6%
Black or African American	55 26.3%	19 18.6%	74 23.8%
White	138 66%	71 69.6%	209 67.2%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	6 2.9%	7 6.9%	13 4.2%
Region of Enrollment (participants) [Number]
United States	209 100%	102 100%	311 100%

Outcome Measures

1. Primary Outcome

Title	Time to AVF Primary Unassisted Patency
Description	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

Outcome Measure Data

Analysis Population Description

Full analysis set includes any patient who was randomized.

Arm/Group Title	Vonapanitase	Placebo
Arm/Group Description	Vonapanitase administered at the time of radiocephalic fistula creation	Placebo administered at the time of radiocephalic fistula creation
Measure Participants	210	103
Median (95% Confidence Interval) [Days]	214	171

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vonapanitase, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.254
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.83
	Confidence Interval	(2-Sided) 95%; 0.61 to 1.14
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Kaplan-Meier Estimate of Secondary AVF Patency
Description	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

Outcome Measure Data

Analysis Population Description

Full analysis set included all patients who were randomized

Arm/Group Title	Vonapanitase	Placebo
Arm/Group Description	Vonapanitase administered at the time of radiocephalic fistula creation	Placebo administered at the time of radiocephalic fistula creation
Measure Participants	210	103
Median (95% Confidence Interval) [days]	NA	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vonapanitase, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.048
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.66
	Confidence Interval	(2-Sided) 95%; 0.43 to 1.00
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Other Pre-specified Outcome

Title	Number of Participants With Unassisted AVF Maturation by Ultrasound
Description	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

Outcome Measure Data

Analysis Population Description

Full analysis set includes any patient who was randomized

Arm/Group Title	Vonapanitase	Placebo
Arm/Group Description	Vonapanitase administered at the time of radiocephalic fistula creation	Placebo administered at the time of radiocephalic fistula creation
Measure Participants	210	103
With Unassisted AVF Maturation	132 63.2%	55 53.9%
Without Unassisted AVF Maturation	78 37.3%	48 47.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vonapanitase, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.109
	Comments
	Method	Chi-squared
	Comments

4. Other Pre-specified Outcome

Title	Number of Participants With Unassisted AVF Use for Hemodialysis
Description	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

Outcome Measure Data

Analysis Population Description

Patients with unassisted use or non-use of their AVF for hemodialysis. Patients with indeterminate use of their AVF were excluded.

Arm/Group Title	Vonapanitase	Placebo
Arm/Group Description	Vonapanitase administered at the time of radiocephalic fistula creation	Placebo administered at the time of radiocephalic fistula creation.
Measure Participants	158	72
New AVF Used Unassisted	62 29.7%	18 17.6%
New AVF Not Used or Assisted Use	96 45.9%	54 52.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vonapanitase, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.035
	Comments
	Method	Chi-squared
	Comments

Adverse Events

Time Frame	All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.
Arm/Group Title	Vonapanitase		Placebo
Arm/Group Description	Vonapanitase administered at the time of radiocephalic fistula creation Vonapanitase		Placebo administered at the time of radiocephalic fistula creation. The placebo is identical in appearance and composition to PRT-201 but lacks the active ingredient. Placebo
All Cause Mortality
	Vonapanitase		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/209 (3.3%)		4/102 (3.9%)
Serious Adverse Events
	Vonapanitase		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	29/209 (13.9%)		15/102 (14.7%)
Blood and lymphatic system disorders
Coagulopathy	0/209 (0%)		1/102 (1%)
Anaemia	1/209 (0.5%)		0/102 (0%)
Cardiac disorders
Cardiac Arrest	1/209 (0.5%)		1/102 (1%)
Cardiac Failure Congestive	1/209 (0.5%)		0/102 (0%)
Coronary Artery Disease	1/209 (0.5%)		0/102 (0%)
Pulseless Electrical Activity	1/209 (0.5%)		0/102 (0%)
Supraventricular Tachycardia	1/209 (0.5%)		0/102 (0%)
Myocardial Infarction	0/209 (0%)		1/102 (1%)
Acute Myocardial Infarction	0/209 (0%)		1/102 (1%)
Gastrointestinal disorders
Colitis	1/209 (0.5%)		0/102 (0%)
Diarrhoea	1/209 (0.5%)		0/102 (0%)
General disorders
Death	1/209 (0.5%)		0/102 (0%)
Chest Pain	0/209 (0%)		1/102 (1%)
Systemic Inflammatory Response Syndrome	0/209 (0%)		1/102 (1%)
Infections and infestations
Sepsis	2/209 (1%)		0/102 (0%)
Arthritis Bacterial	1/209 (0.5%)		0/102 (0%)
Cellulitis	1/209 (0.5%)		0/102 (0%)
infection	0/209 (0%)		1/102 (1%)
Pneumonia	0/209 (0%)		3/102 (2.9%)
Injury, poisoning and procedural complications
Arteriovenous Fistula Thrombosis	2/209 (1%)		1/102 (1%)
Injury	1/209 (0.5%)		0/102 (0%)
Limb Injury	1/209 (0.5%)		0/102 (0%)
Metabolism and nutrition disorders
Fluid Overload	2/209 (1%)		1/102 (1%)
Hyperkalaemia	2/209 (1%)		0/102 (0%)
Gout	0/209 (0%)		1/102 (1%)
Ketoacidosis	0/209 (0%)		1/102 (1%)
Nervous system disorders
Hypoxic-Ischaemic Encephalopathy	1/209 (0.5%)		0/102 (0%)
Metabolic Encephalopathy	1/209 (0.5%)		1/102 (1%)
Psychiatric disorders
Major Depression	1/209 (0.5%)		0/102 (0%)
Renal and urinary disorders
Renal Failure Acute	1/209 (0.5%)		0/102 (0%)
Renal Failure Chronic	0/209 (0%)		1/102 (1%)
Respiratory, thoracic and mediastinal disorders
Chronic Obstructive Pulmonary Disease	2/209 (1%)		0/102 (0%)
Dyspnoea	2/209 (1%)		0/102 (0%)
Acute Respiratory Failure	1/209 (0.5%)		0/102 (0%)
Haemoptyis	1/209 (0.5%)		0/102 (0%)
Pleural Effusion	1/209 (0.5%)		0/102 (0%)
Skin and subcutaneous tissue disorders
Diabetic Foot	1/209 (0.5%)		0/102 (0%)
Decubitus Ulcer	0/209 (0%)		1/102 (1%)
Vascular disorders
Deep Vein Thrombosis	1/209 (0.5%)		0/102 (0%)
Hypertensive Crisis	1/209 (0.5%)		1/102 (1%)
Shock	1/209 (0.5%)		0/102 (0%)
Steal Syndrome	1/209 (0.5%)		0/102 (0%)
Vascular Stenosis	1/209 (0.5%)		0/102 (0%)
Other (Not Including Serious) Adverse Events
	Vonapanitase		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	149/209 (71.3%)		84/102 (82.4%)
Injury, poisoning and procedural complications
Procedural Pain	10/209 (4.8%)		6/102 (5.9%)
Arteriovenous fistula thrombosis	41/209 (19.6%)		27/102 (26.5%)
Nervous system disorders
Hypoaesthesia	11/209 (5.3%)		5/102 (4.9%)
Vascular disorders
Vascular Stenosis	80/209 (38.3%)		41/102 (40.2%)
Haematoma	7/209 (3.3%)		5/102 (4.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.