Efﬁcacy End Points

Penile measurement.

Mean penile curvature at

baseline was 54.4

15.1 degrees for subjects random-

ized to CCh and 50.6

15.1 degrees for those on placebo.

A mean change in penile curvature of

16.3

14.6

degrees was observed for CCh treatment, representing a

mean 29.7% improvement per patient, compared

with the mean change of

5.4

13.8 degrees for

placebo, representing a mean 11% improvement per

patient (curvature change and improvement vs pla-

cebo p

0.001 and 0.001, respectively,

ﬁg. 2

Decreased penile curvature was observed with

time beginning at week 6 and continuing through

week 36 with signiﬁcant differences in the mean

change from baseline observed between CCh treated

and placebo subjects at weeks 18 (

14.5

12.9 vs

4.4

11.6), 24 (

15.0

14.2 vs

6.9

12.3) and

36 (

16.6

14.7 vs

5.4

14.0, each p

0.007).

Statistical testing was not done at earlier time

points. At least 25% improvement in penile curva-

ture was noted in 61% of CCh treated subjects com-

pared to only 25% in those on placebo. After CCh

treatment small mean increases in penile length,

and small mean decreases in plaque length, width

and area were also observed.

Questionnaire responses.

Each subject completed

the PD-PRO questionnaire to determine the impact

of PD on quality of life. CCh treated subjects had a

signiﬁcantly better score on the PD symptom bother

domain than those on placebo (p

0.05). There were

no statistically signiﬁcant differences when compar-

ing CCh and placebo for the other 3 domains. At

week 36 a low to moderate correlation was observed

between the degree of penile curvature, and the

PD-PRO domains of symptom bother (r

0.22,

0.01), intercourse discomfort (r

0.2, p

0.02)

and intercourse constraint (r

0.42, p

0.001). All

subjects also completed the IIEF questionnaire to

determine erectile function but no signiﬁcant differ-

ences were observed for CCh vs placebo.

Safety End Points

Most patients had TEAEs or treatment related AEs

that were at most mild or moderate in severity, as

assessed by the investigator.

Table 3

lists the most

common treatment related AEs, that is those that

developed in 5 or more subjects. Contusion was de-

ﬁned as any penile bruising/ecchymosis. CCh treated

subjects had a signiﬁcantly higher rate of treatment

related injection site bruising, edema and pain than

those on placebo (p

0.001). Erectile function did not

change during the study course in 4 of the 5 patients

with painful erection on CCh.

Five patients experienced at least 1 SAE but no

treatment related SAEs were observed. Two sub-

jects discontinued CCh prematurely due to TEAEs,

including injection site bruising, edema and rash in

1 without modeling, and penile edema and penile

pain in 1 with modeling. Of the 147 patients 137

(93.2%) received all 6 injections according to the

protocol. No clinically meaningful effects were ob-

served on laboratory or vital sign parameters.

In regard to immunogenicity 78 of the 103 pa-

tients (75.7%) on CCh had positive antibodies to

AUX-I after the ﬁrst treatment cycle. All patients on

CCh showed positive antibodies to AUX-I and II by

week 36. No subject reported a TEAE indicating a

clinically signiﬁcant systemic immunological response

to CCh. No systemic immunological events were re-

ported.

Efﬁcacy End Points by Modeling

Penile measurement.

After CCh injection enzymat-

ically weakens the PD plaque it is anticipated that

modeling would further decrease the restrictive ef-

fects of the plaque on tunica albuginea expansion

during erection. Subjects who underwent the mod-

eling procedure showed a mean 32.4% improvement

in penile curvature (mean change

17.5

15.3 de-

grees) for CCh treatment vs a mean 2.5% worsening

in curvature (mean change 0.6

13.2 degrees) for

placebo (p

0.001,

ﬁg. 2

). Subjects without mod-

eling experienced a 27.1% mean improvement in

penile curvature (mean change

15.0

14.0 de-

grees) when treated with CCh, which did not statis-

tically signiﬁcantly differ from the 27.9% mean im-

provement (mean change

13.0

10.7 degrees)

Table 2.

Patient reported PD history

No. Modeling (%)

No. No Modeling (%)

CCh

Placebo

CCh

Placebo

Overall

Erect penile trauma:

40 (74.1)

19 (95.0)

44 (77.2)

11 (68.8)

Yes

14 (25.9)

1 (5.0)

13 (22.8)

5 (31.3)

Penile pain history (mos):

None

31 (57.4)

10 (50.0)

30 (52.6)

9 (56.3)

Less than 3

8 (14.8)

2 (10.0)

9 (15.8)

2 (12.5)

3–6

4 (7.4)

5 (25.0)

4 (7.0)

2 (12.5)

6–9

2 (3.7)

6 (10.5)

1 (6.3)

Greater than 9

9 (16.7)

3 (15.0)

8 (14.0)

2 (12.5)

Penile shortening (inch):

None

18 (33.3)

2 (10.0)

19 (33.3)

3 (18.8)

1 or Less

24 (44.4)

13 (65.0)

23 (40.4)

6 (37.5)

Greater than 1

12 (22.2)

5 (25.0)

15 (26.3)

7 (43.8)

Malformation:

Dorsal

44 (81.5)

17 (85.0)

47 (82.5)

15 (93.8)

Lateral rt

8 (14.8)

3 (15.0)

7 (12.3)

6 (37.5)

Lateral lt

22 (40.7)

6 (30.0)

18 (31.6)

2 (12.5)

ED:

28 (51.9)

13 (65.0)

32 (56.1)

9 (56.3)

Yes

26 (48.1)

7 (35.0)

25 (43.9)

7 (43.8)

History (yrs):

1 or Less

8 (14.8)

5 (25.0)

15 (26.3)

7 (43.8)

1.1–2

17 (31.5)

5 (25.0)

20 (35.1)

5 (31.3)

2.1–3

13 (24.1)

6 (30.0)

5 (8.8)

1 (6.3)

Greater than 3

16 (29.6)

4 (20.0)

17 (29.8)

3 (18.8)

PHASE 2B STUDY OF COLLAGENASE CLOSTRIDIUM HISTOLYTICUM

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