Trial Outcomes & Findings for A Study of PRT-201 Administered Immediately After Radiocephalic Arteriovenous Fistula(AVF) Creation in Patients With Chronic Kidney Disease (CKD) (PATENCY-1) (NCT NCT02110901)

NCT ID: NCT02110901

Last Updated: 2019-07-09

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 349 participants
• Primary outcome timeframe: Days from AVF creation until the first occurrence of either access thrombosis or procedure to restore or maintain patency, assessed up to 1 year
• Results posted on: 2019-07-09

Participant Flow

349 patients signed informed consent; 313 patients were randomized; 311 were treated

Participants were excluded from participation if they did not have a radiocephalic AVF created at the time of surgery.

Participant milestones

Measure	Vonapanitase Vonapanitase administered at the time of radiocephalic fistula creation	Placebo Placebo administered at the time of radiocephalic fistula creation
Overall Study STARTED	209	102
Overall Study COMPLETED	179	88
Overall Study NOT COMPLETED	30	14

Reasons for withdrawal

Measure	Vonapanitase Vonapanitase administered at the time of radiocephalic fistula creation	Placebo Placebo administered at the time of radiocephalic fistula creation
Overall Study Death	6	3
Overall Study Lost to Follow-up	12	8
Overall Study Withdrawal by Subject	7	3
Overall Study received a kidney transplant	5	0

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Vonapanitase n=209 Participants Single application administered over 10 minutes at the time of fistula creation.	Placebo n=102 Participants Single application administered over 10 minutes at the time of fistula creation.	Total n=311 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	143 Participants n=5 Participants	71 Participants n=7 Participants	214 Participants n=5 Participants
Age, Categorical >=65 years	66 Participants n=5 Participants	31 Participants n=7 Participants	97 Participants n=5 Participants
Sex: Female, Male Female	36 Participants n=5 Participants	26 Participants n=7 Participants	62 Participants n=5 Participants
Sex: Female, Male Male	173 Participants n=5 Participants	76 Participants n=7 Participants	249 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	29 Participants n=5 Participants	19 Participants n=7 Participants	48 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	180 Participants n=5 Participants	83 Participants n=7 Participants	263 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Asian	6 Participants n=5 Participants	5 Participants n=7 Participants	11 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Black or African American	55 Participants n=5 Participants	19 Participants n=7 Participants	74 Participants n=5 Participants
Race (NIH/OMB) White	138 Participants n=5 Participants	71 Participants n=7 Participants	209 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	6 Participants n=5 Participants	7 Participants n=7 Participants	13 Participants n=5 Participants
Region of Enrollment United States	209 participants n=5 Participants	102 participants n=7 Participants	311 participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Vonapanitase n=210 Participants Vonapanitase administered at the time of radiocephalic fistula creation	Placebo n=103 Participants Placebo administered at the time of radiocephalic fistula creation
Time to AVF Primary Unassisted Patency	214 Days Interval 163.0 to 322.0	171 Days Interval 126.0 to 285.0

PRIMARY outcome

Timeframe: 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

Kaplan-Meier Estimate of median time from AVF creation until AVF abandonment (secondary patency)

Outcome measures

Measure	Vonapanitase n=210 Participants Vonapanitase administered at the time of radiocephalic fistula creation	Placebo n=103 Participants Placebo administered at the time of radiocephalic fistula creation
Kaplan-Meier Estimate of Secondary AVF Patency	NA days The median time to AVF abandonment based on Kaplan-Meier estimates was not reached in this trial	NA days The median time to AVF abandonment based on Kaplan-Meier estimates was not reached in this trial

OTHER_PRE_SPECIFIED outcome

Timeframe: Assessed 3 months after AVF creation

Population: Full analysis set includes any patient who was randomized

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.

Outcome measures

Measure	Vonapanitase n=210 Participants Vonapanitase administered at the time of radiocephalic fistula creation	Placebo n=103 Participants Placebo administered at the time of radiocephalic fistula creation
Number of Participants With Unassisted AVF Maturation by Ultrasound With Unassisted AVF Maturation	132 Participants	55 Participants
Number of Participants With Unassisted AVF Maturation by Ultrasound Without Unassisted AVF Maturation	78 Participants	48 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

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.

Outcome measures

Measure	Vonapanitase n=158 Participants Vonapanitase administered at the time of radiocephalic fistula creation	Placebo n=72 Participants Placebo administered at the time of radiocephalic fistula creation
Number of Participants With Unassisted AVF Use for Hemodialysis New AVF Used Unassisted	62 Participants	18 Participants
Number of Participants With Unassisted AVF Use for Hemodialysis New AVF Not Used or Assisted Use	96 Participants	54 Participants

Adverse Events

Vonapanitase

Serious events: 29 serious events

Other events: 149 other events

Deaths: 7 deaths

Placebo

Serious events: 15 serious events

Other events: 84 other events

Deaths: 4 deaths

Serious adverse events

Measure	Vonapanitase n=209 participants at risk Vonapanitase administered at the time of radiocephalic fistula creation Vonapanitase	Placebo n=102 participants at risk 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
Blood and lymphatic system disorders Coagulopathy	0.00% 0/209 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.	0.98% 1/102 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.
Cardiac disorders Cardiac Arrest	0.48% 1/209 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.	0.98% 1/102 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.
Cardiac disorders Cardiac Failure Congestive	0.48% 1/209 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.	0.00% 0/102 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.
Cardiac disorders Coronary Artery Disease	0.48% 1/209 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.	0.00% 0/102 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.
Cardiac disorders Pulseless Electrical Activity	0.48% 1/209 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.	0.00% 0/102 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.
Cardiac disorders Supraventricular Tachycardia	0.48% 1/209 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.	0.00% 0/102 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.
Cardiac disorders Myocardial Infarction	0.00% 0/209 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.	0.98% 1/102 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.
Cardiac disorders Acute Myocardial Infarction	0.00% 0/209 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.	0.98% 1/102 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.
Gastrointestinal disorders Colitis	0.48% 1/209 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.	0.00% 0/102 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.
Gastrointestinal disorders Diarrhoea	0.48% 1/209 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.	0.00% 0/102 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.
General disorders Death	0.48% 1/209 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.	0.00% 0/102 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.
General disorders Chest Pain	0.00% 0/209 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.	0.98% 1/102 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.
General disorders Systemic Inflammatory Response Syndrome	0.00% 0/209 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.	0.98% 1/102 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.
Infections and infestations Sepsis	0.96% 2/209 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.	0.00% 0/102 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.
Infections and infestations Arthritis Bacterial	0.48% 1/209 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.	0.00% 0/102 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.
Infections and infestations Cellulitis	0.48% 1/209 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.	0.00% 0/102 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.
Infections and infestations infection	0.00% 0/209 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.	0.98% 1/102 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.
Infections and infestations Pneumonia	0.00% 0/209 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.	2.9% 3/102 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.
Blood and lymphatic system disorders Anaemia	0.48% 1/209 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.	0.00% 0/102 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.
Injury, poisoning and procedural complications Arteriovenous Fistula Thrombosis	0.96% 2/209 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.	0.98% 1/102 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.
Injury, poisoning and procedural complications Injury	0.48% 1/209 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.	0.00% 0/102 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.
Injury, poisoning and procedural complications Limb Injury	0.48% 1/209 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.	0.00% 0/102 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.
Metabolism and nutrition disorders Fluid Overload	0.96% 2/209 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.	0.98% 1/102 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.
Metabolism and nutrition disorders Hyperkalaemia	0.96% 2/209 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.	0.00% 0/102 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.
Metabolism and nutrition disorders Gout	0.00% 0/209 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.	0.98% 1/102 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.
Metabolism and nutrition disorders Ketoacidosis	0.00% 0/209 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.	0.98% 1/102 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.
Nervous system disorders Hypoxic-Ischaemic Encephalopathy	0.48% 1/209 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.	0.00% 0/102 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.
Nervous system disorders Metabolic Encephalopathy	0.48% 1/209 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.	0.98% 1/102 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.
Psychiatric disorders Major Depression	0.48% 1/209 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.	0.00% 0/102 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.
Renal and urinary disorders Renal Failure Acute	0.48% 1/209 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.	0.00% 0/102 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.
Renal and urinary disorders Renal Failure Chronic	0.00% 0/209 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.	0.98% 1/102 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.
Respiratory, thoracic and mediastinal disorders Chronic Obstructive Pulmonary Disease	0.96% 2/209 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.	0.00% 0/102 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.96% 2/209 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.	0.00% 0/102 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.
Respiratory, thoracic and mediastinal disorders Acute Respiratory Failure	0.48% 1/209 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.	0.00% 0/102 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.
Respiratory, thoracic and mediastinal disorders Haemoptyis	0.48% 1/209 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.	0.00% 0/102 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.
Respiratory, thoracic and mediastinal disorders Pleural Effusion	0.48% 1/209 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.	0.00% 0/102 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.
Skin and subcutaneous tissue disorders Diabetic Foot	0.48% 1/209 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.	0.00% 0/102 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.
Skin and subcutaneous tissue disorders Decubitus Ulcer	0.00% 0/209 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.	0.98% 1/102 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.
Vascular disorders Deep Vein Thrombosis	0.48% 1/209 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.	0.00% 0/102 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.
Vascular disorders Hypertensive Crisis	0.48% 1/209 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.	0.98% 1/102 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.
Vascular disorders Shock	0.48% 1/209 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.	0.00% 0/102 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.
Vascular disorders Steal Syndrome	0.48% 1/209 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.	0.00% 0/102 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.
Vascular disorders Vascular Stenosis	0.48% 1/209 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.	0.00% 0/102 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.

Other adverse events

Measure	Vonapanitase n=209 participants at risk Vonapanitase administered at the time of radiocephalic fistula creation Vonapanitase	Placebo n=102 participants at risk 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
Injury, poisoning and procedural complications Procedural Pain	4.8% 10/209 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.	5.9% 6/102 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.
Injury, poisoning and procedural complications Arteriovenous fistula thrombosis	19.6% 41/209 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.	26.5% 27/102 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.
Nervous system disorders Hypoaesthesia	5.3% 11/209 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.	4.9% 5/102 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.
Vascular disorders Vascular Stenosis	38.3% 80/209 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.	40.2% 41/102 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.
Vascular disorders Haematoma	3.3% 7/209 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.	4.9% 5/102 • All adverse events through Week 6 were collected. Week 6-Month 12 only AEs associated with the AVF extremity were collected.

Additional Information

Steven Burke, MD

Proteon Therapeutics, Inc

Phone: 781-890-0102

Email: Clinical@ProteonTx.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place