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PROTEON THERAPEUTICS INC filed this Form S-1 on 09/16/2014
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        In a larger trial of brachiocephalic AVFs, we expect that the occurrence of patency loss due to central stenosis would be evenly distributed between treatment groups. In the Phase 3 clinical trials we have planned, we expect that patency loss due to central stenosis would be rare since we intend to enroll radiocephalic AVF patients exclusively and radiocephalic AVFs rarely suffer from patency loss due to central stenosis because of lower blood flow. In our Phase 2 trial, no radiocephalic AVF in any group lost primary patency due to central stenosis.

    Secondary and other endpoints

        PRT-201 showed results consistent with a beneficial drug effect on multiple secondary efficacy endpoints. The prespecified efficacy endpoints were unassisted maturation, secondary patency, use for hemodialysis and hemodynamically significant lumen stenosis. In addition, we performed a prespecified efficacy analysis of average rate of procedures to restore or maintain AVF patency, a component of our primary endpoint. As with the primary efficacy analyses, we performed a number of prespecified and exploratory analyses of the data from this Phase 2 trial.

    Unassisted maturation.  Maturation is necessary for use of an AVF for hemodialysis. Unassisted maturation was defined as achieving maturation at three months without an intervention. Maturation was assessed using ultrasound measuring blood flow and lumen vein diameter. All ultrasounds were reviewed by a central reader masked to treatment assignment and AVF outcome. Two well-accepted criteria for measuring maturation were used, as shown in the footnotes in the table below. The 30 microgram dose, which we intend to study in our Phase 3 trials, showed statistically significant improvement in maturation at Month 3, with more benefit seen in patients receiving radiocephalic AVFs (figure below) than in patients receiving brachiocephalic AVFs. In the subset of patients with brachiocephalic AVFs, there was a trend toward improvement in unassisted maturation at both the 10 and 30 microgram doses.

Unassisted Maturation at Three Months—% of Patients (p-Value vs. Placebo)

  Placebo   PRT-201
10 micrograms
30 micrograms

All AVFs


Number of Patients

  N=39   N=39   N=37

Percentage Mature NKF-KDOQI(1)

  46%   64% (p=0.11)   70% (p=0.03)

Percentage Mature Robbin(2)

  67%   87% (p=0.03)   92% (p<0.01)

Radiocephalic AVFs


Number of Patients

  N=17   N=19   N=14

Percentage Mature NKF-KDOQI(1)

  24%   37% (p=0.48)   57% (p=0.08)

Percentage Mature Robbin(2)

  47%   74% (p=0.17)   93% (p<0.01)

Brachiocephalic AVFs


Number of Patients

  N=22   N=20   N=23

Percentage Mature NKF-KDOQI(1)

  64%   90% (p=0.07)   78% (p=0.34)

Percentage Mature Robbin(2)

  82%   100% (p=0.11)   91% (p=0.41)

Note:    Prespecified analysis.

National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF-KDOQI) maturation is defined as average vein lumen diameter ³6 millimeters and an outflow vein blood flow rate ³600 milliliters/minute.

Robbin maturation is defined as average vein lumen diameter ³4 millimeters and an outflow vein blood flow rate ³500 milliliters/minute.