A Study of Vonapanitase (PRT-201) Administered Immediately After Radiocephalic Arteriovenous Fistula(AVF) Creation in Patients With Chronic Kidney Disease (CKD) (PATENCY-2)

• Sponsor: Proteon Therapeutics (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02414841
• Collaborator: (none)
• Enrollment: 696
• Locations: 41
• Arms: 2
• Actual Duration (Months): 45
• Patients Per Site: 17
• Patients Per Site Per Month: 0.4

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Kidney Disease	Drug: Vonapanitase; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 696 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 Vonapanitase (PRT- 201) Administered Immediately After Radiocephalic Arteriovenous Fistula Creation in Patients With Chronic Kidney Disease
• Actual Study Start Date: Aug 1, 2015
• Actual Primary Completion Date: Feb 1, 2018
• Actual Study Completion Date: May 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Vonapanitase Vonapanitase administered at the time of radiocephalic fistula creation	Drug: Vonapanitase; Other Names: PRT-201
Placebo Comparator: Placebo Placebo administered at the time of radiocephalic fistula creation	Drug: Placebo

Outcome Measures

Primary Outcome Measures

1. 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)

2. 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.

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 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.

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	Banner University Medical Center Tucson	Tucson	Arizona	United States	85724
4	AKDHC Medical Research Services, LLc	Tucson	Arizona	United States	85745
5	VA Loma Linda Healthcare System	Loma Linda	California	United States	92357
6	VA Medical Center Long Beach	Long Beach	California	United States	90822
7	Keck University Hospital at USC	Los Angeles	California	United States	90033
8	Kaiser Permanente	San Diego	California	United States	92120
9	California Institute of Renal Research	San Diego	California	United States	92123
10	Kaiser Permanente Northern California	San Francisco	California	United States	94118
11	University of Chicago	Chicago	Illinois	United States	60637
12	RenalCare Associates, S.C.	Peoria	Illinois	United States	61603
13	Lutheran Hospital Network of Indiana	Fort Wayne	Indiana	United States	46804
14	The University of Iowa Hospitals and Clinics	Iowa City	Iowa	United States	52242
15	University of Louisville	Louisville	Kentucky	United States	40202
16	Tulane University	New Orleans	Louisiana	United States	70112
17	Maine Medical Center	Portland	Maine	United States	04102
18	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
19	University of Massachusetts Medical Center	Worcester	Massachusetts	United States	01655
20	VA Ann Arbor Healthcare System	Ann Arbor	Michigan	United States	48105
21	Henry Ford Hospital	Detroit	Michigan	United States	48202
22	Greenwood Leflore Hospital	Greenwood	Mississippi	United States	38930
23	Saint Luke's Hospital	Kansas City	Missouri	United States	64111
24	New York Presbyterian Hospital-Weill Cornell Medical Center	New York	New York	United States	10065
25	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina	United States	27599
26	Wake Forest	Winston-Salem	North Carolina	United States	27157
27	Cleveland Clinic	Cleveland	Ohio	United States	44195
28	Lehigh Valley Health Network	Allentown	Pennsylvania	United States	18103
29	VA Pittsburg Healthcare System	Pittsburgh	Pennsylvania	United States	15240
30	SC Nephrology and Hypertension Center, Inc.	Orangeburg	South Carolina	United States	29118
31	Knoxville Kidney Center	Knoxville	Tennessee	United States	37923
32	Cardiothoracis and Vascular Surgeons	Austin	Texas	United States	78756
33	Baylor College of Medicine	Houston	Texas	United States	77030
34	The Methodist Hospital	Houston	Texas	United States	77030
35	Lake Washington Vascular Center	Bellevue	Washington	United States	98004
36	University of Wisconsin School of Medicine and PH	Madison	Wisconsin	United States	53792
37	University of Alberta	Edmonton	Alberta	Canada	T6G2B7
38	Vancouver General Hospital	Vancouver	British Columbia	Canada	V5Z 1M9
39	London Health Science Center	London	Ontario	Canada	N6A 5W9
40	University Health Network Toronto General Hospital	Toronto	Ontario	Canada	M5G 2C4
41	McGill University Health Centre- Royal Victoria Hospital	Montreal	Quebec	Canada	H4A 3J1

Sponsors and Collaborators

• Proteon Therapeutics

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 9, 2018

More Information

Publications

None provided.

• Responsible Party: Proteon Therapeutics
• ClinicalTrials.gov Identifier: NCT02414841
• Other Study ID Numbers: PRT-201-320
• First Posted: Apr 13, 2015
• Last Update Posted: Aug 13, 2019
• Last Verified: Jul 1, 2019

• Keywords provided by Proteon Therapeutics: radiocephalic; arteriovenous fistula; AVF; hemodialysis; PRT-201; vonapanitase; vascular access; kidney; renal; PATENCY-2; secondary patency; fistula abandonment; use for hemodialysis
• Additional relevant MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Arteriovenous Fistula; Fistula

Study Results

Participant Flow

Recruitment Details	696 patients signed informed consent; 613 patients were randomized; 603 were treated
Pre-assignment Detail	Participants were excluded if they did not have a radiocephalic fistula created at the time of surgery

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 Placebo
Period Title: Overall Study
STARTED	405	208
COMPLETED	349	175
NOT COMPLETED	56	33

Baseline Characteristics

Arm/Group Title	Vonapanitase	Placebo	Total
Arm/Group Description	Vonapanitase administered at the time of radiocephalic fistula creation	Placebo administered at the time of radiocephalic fistula creation	Total of all reporting groups
Overall Participants	405	208	613
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	277 68.4%	132 63.5%	409 66.7%
>=65 years	128 31.6%	76 36.5%	204 33.3%
Sex: Female, Male (Count of Participants)
Female	101 24.9%	46 22.1%	147 24%
Male	304 75.1%	162 77.9%	466 76%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	3 0.7%	0 0%	3 0.5%
Asian	19 4.7%	10 4.8%	29 4.7%
Native Hawaiian or Other Pacific Islander	3 0.7%	1 0.5%	4 0.7%
Black or African American	104 25.7%	45 21.6%	149 24.3%
White	269 66.4%	149 71.6%	418 68.2%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	7 1.7%	3 1.4%	10 1.6%
Region of Enrollment (participants) [Number]
Canada	41 10.1%	18 8.7%	59 9.6%
United States	358 88.4%	186 89.4%	544 88.7%

Outcome Measures

1. 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 to AVF abandonment (secondary patency), assessed up to 1 year.

Outcome Measure Data

Analysis Population Description

Full analysis set includes all 613 patients who were randomized

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 of vonapanitase but lacks the active ingredient. Placebo
Measure Participants	405	208
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	0.932
	Comments
	Method	Log Rank
	Comments	Weighted
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.96
	Confidence Interval	(2-Sided) 95%; 0.67 to 1.39
	Parameter Dispersion	Type: Value:
	Estimation Comments	Performed as sensitivity analysis

2. Primary Outcome

Title	Number of Participants With AVF Use for Hemodialysis
Description	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

Outcome Measure Data

Analysis Population Description

Patients having use or non-use of their AVF. 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	405	208
AVF Used	209 51.6%	99 47.6%
AVF Not Used	91 22.5%	53 25.5%
Indeterminant AVF Use	105 25.9%	56 26.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vonapanitase, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.328
	Comments
	Method	Chi-squared
	Comments

Adverse Events

Time Frame	All Adverse Events (AE) through Week 4; Only AEs associated with the AVF extremity Week 4-Month 12.
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. The placebo is identical in appearance and composition of vonapanitase but lacks the active ingredient.
All Cause Mortality
	Vonapanitase		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/399 (4.3%)		14/204 (6.9%)
Serious Adverse Events
	Vonapanitase		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	48/399 (12%)		30/204 (14.7%)
Cardiac disorders
Pulseless Electrical Activity	0/399 (0%)		1/204 (0.5%)
Cardiac Arrest	2/399 (0.5%)		5/204 (2.5%)
Acute Myocardial Infarction	0/399 (0%)		1/204 (0.5%)
Cardiac Failure Congestive	1/399 (0.3%)		0/204 (0%)
Cardio-Respiratory Arrest	1/399 (0.3%)		0/204 (0%)
Coronary Artery Disease	1/399 (0.3%)		0/204 (0%)
Cardiac Failure	1/399 (0.3%)		0/204 (0%)
Myocardial infarction	1/399 (0.3%)		0/204 (0%)
Gastrointestinal disorders
Lower Gastrointestinal Haemorrhage	0/399 (0%)		1/204 (0.5%)
Pancreatitis	1/399 (0.3%)		0/204 (0%)
Pancreatitis Acute	1/399 (0.3%)		0/204 (0%)
Small Intestinal Obstruction	1/399 (0.3%)		0/204 (0%)
Gastrointestinal Haemorrhage	1/399 (0.3%)		0/204 (0%)
General disorders
Pyrexia	0/399 (0%)		1/204 (0.5%)
Device Kink	1/399 (0.3%)		0/204 (0%)
Chest Pain	1/399 (0.3%)		0/204 (0%)
Unknown Cause of Death	1/399 (0.3%)		0/204 (0%)
Sudden Death	1/399 (0.3%)		0/204 (0%)
Generalised Oedema	1/399 (0.3%)		0/204 (0%)
Infections and infestations
Sepsis	2/399 (0.5%)		1/204 (0.5%)
Cytomegalovirus infection	0/399 (0%)		1/204 (0.5%)
Pneumonia	4/399 (1%)		4/204 (2%)
Pulmonary Tuberculosis	0/399 (0%)		1/204 (0.5%)
Septic Shock	0/399 (0%)		1/204 (0.5%)
Post Procedural Infection	1/399 (0.3%)		0/204 (0%)
Osteomyelitis	1/399 (0.3%)		0/204 (0%)
Bacteraemia	1/399 (0.3%)		0/204 (0%)
Injury, poisoning and procedural complications
Humerus fracture	0/399 (0%)		1/204 (0.5%)
Arteriovenous Fistula Thrombosis	7/399 (1.8%)		1/204 (0.5%)
Procedural Pain	2/399 (0.5%)		0/204 (0%)
Seroma	1/399 (0.3%)		0/204 (0%)
Metabolism and nutrition disorders
Fluid Overload	0/399 (0%)		3/204 (1.5%)
Calciphylaxis	1/399 (0.3%)		0/204 (0%)
Hyperkalaemia	1/399 (0.3%)		0/204 (0%)
Hypoglycaemia	1/399 (0.3%)		0/204 (0%)
Musculoskeletal and connective tissue disorders
Rhabdomyolysis	0/399 (0%)		1/204 (0.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma	1/399 (0.3%)		0/204 (0%)
Pancreatic Carcinoma	1/399 (0.3%)		0/204 (0%)
Nervous system disorders
Cerebral Haemorrhage	0/399 (0%)		1/204 (0.5%)
Syncope	1/399 (0.3%)		0/204 (0%)
Presyncope	1/399 (0.3%)		0/204 (0%)
Psychiatric disorders
Confusional State	1/399 (0.3%)		0/204 (0%)
Renal and urinary disorders
Renal Failure	1/399 (0.3%)		2/204 (1%)
Renal Failure Chronic	1/399 (0.3%)		2/204 (1%)
Renal Failure Acute	1/399 (0.3%)		1/204 (0.5%)
Azotaemia	1/399 (0.3%)		0/204 (0%)
Respiratory, thoracic and mediastinal disorders
Pleural Effusion	0/399 (0%)		1/204 (0.5%)
Pulmonary Embolism	1/399 (0.3%)		0/204 (0%)
Aspiration	1/399 (0.3%)		0/204 (0%)
Acute Respiratory Failure	1/399 (0.3%)		0/204 (0%)
Pulmonary Oedema	1/399 (0.3%)		0/204 (0%)
Surgical and medical procedures
Toe Surgery	0/399 (0%)		1/204 (0.5%)
Vascular disorders
Venous Thrombosis	0/399 (0%)		1/204 (0.5%)
Steal Syndrome	1/399 (0.3%)		1/204 (0.5%)
Hypertension	0/399 (0%)		1/204 (0.5%)
Deep Vein Thrombosis	0/399 (0%)		1/204 (0.5%)
Haematoma	0/399 (0%)		2/204 (1%)
Collateral Circulation	2/399 (0.5%)		0/204 (0%)
Vascular Stenosis	2/399 (0.5%)		0/204 (0%)
Circulatory Collapse	1/399 (0.3%)		0/204 (0%)
Other (Not Including Serious) Adverse Events
	Vonapanitase		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	247/399 (61.9%)		135/204 (66.2%)
General disorders
Local Swelling	20/399 (5%)		4/204 (2%)
Injury, poisoning and procedural complications
Arteriovenous Fistula Thrombosis	67/399 (16.8%)		38/204 (18.6%)
Vascular disorders
Vascular Stenosis	140/399 (35.1%)		85/204 (41.7%)
Haematoma	20/399 (5%)		8/204 (3.9%)

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.