Phase 2b Study of the Clinical Efﬁcacy and Safety of Collagenase

Clostridium Histolyticum in Patients With Peyronie Disease

Martin Gelbard,*,† Larry I. Lipshultz,‡ James Tursi,§ Ted Smith,§ Greg Kaufman§

and Laurence A. Levine

From the Urology Associates Medical Group (MG), Burbank, California, Baylor College of Medicine (LIL), Houston, Texas, Auxilium

Pharmaceuticals, Inc. (JT, TS, GK), Malvern, Pennsylvania, and Rush University (LAL), Chicago, Illinois

Purpose:

Collagenase Clostridium histolyticum is an investigational nonsurgical

treatment for Peyronie disease. In this phase 2b, double-blind, randomized,

placebo controlled study we determined the safety and efﬁcacy of collagenase

C. histolyticum and assessed a patient reported outcome questionnaire.

Materials and Methods:

A total of 147 subjects were randomized into 4 groups to

receive collagenase C. histolyticum or placebo (3:1) with or without penile plaque

modeling (1:1). Per treatment cycle 2 injections of collagenase C. histolyticum

(0.58 mg) were given 24 to 72 hours apart. Subjects received up to 3 cycles at

6-week intervals. When designated, investigator modeling was done 24 to 72

hours after the second injection of each cycle. We evaluated penile curvature by

goniometer measurement, patient reported outcomes and adverse event proﬁles.

Results:

After collagenase C. histolyticum treatment signiﬁcant improvements

in penile curvature (29.7% vs 11.0%, p

0.001) and patient reported outcome

symptom bother scores (p

0.05) were observed compared to placebo. In

modeled subjects 32.4% improvement in penile curvature was observed in

those on collagenase C. histolyticum compared to 2.5% worsening of curvature

in those on placebo (p

0.001). Those treated with collagenase C. histolyticum

who underwent modeling also showed improved Peyronie disease symptom

bother scores (p

0.004). In subjects without modeling there were minimal

differences between the active and placebo cohorts. Most adverse events in the

collagenase C. histolyticum group occurred at the injection site and were mild

or moderate in severity. No treatment related serious adverse events were

reported.

Conclusions:

Collagenase C. histolyticum treatment was well tolerated. We

noted signiﬁcant improvement in penile curvature and patient reported outcome

symptom bother scores, suggesting that this may be a safe, nonsurgical alterna-

tive for Peyronie disease.

Key Words:

penis; penile induration; collagenase VII-S, Clostridium

histolyticum; drug toxicity; questionnaires

OLLAGEN

based plaque in the tunica

albuginea associated with PD leads to

various penile malformations, includ-

ing curvature, indentation, narrow-

ing, shortening, hourglass-like shape

and buckling erection.

1,2

In addition

to physical symptoms, the psycholog-

ical impact of PD should be consid-

ered since studies show that many pa-

tients experience clinical depression,

emotional and relationship difﬁcul-

ties, and poor self-esteem.

3–5

Some de-

gree of ED is also common in men with

PD.

2,6

Causes of ED may be physical due

Abbreviations

and Acronyms

adverse event

CCh

collagenase Clostridium

histolyticum

erectile dysfunction

IIEF

International Index of

Erectile Function

ITT

intent to treat

mITT

modiﬁed ITT

Peyronie disease

PD-PRO

PD patient reported

outcome

SAE

serious TEAE

TEAE

treatment emergent AE

Submitted for publication August 22, 2011

Study received institutional review board ap-

proval at all sites.

Supported by Auxilium Pharmaceuticals.

* Correspondence: Urology Associates Medical

Group, 2601 West Alameda Ave., Suite 416, Bur-

bank, California 91505 (telephone: 818-843-1702;

FAX: 818-843-0380; e-mail:

mgelbard@ucla.edu

† Financial interest and/or other relationship

with Auxilium and Biospeciﬁcs.

‡ Financial interest and/or other relationship

with Allergan, Auxilium, American Medical Sys-

tems and Repros Therapeutics.

§ Financial interest and/or other relationship

with Auxilium.

Financial interest and/or other relationship

with Auxilium, Coloplast, Lilly, Astellas, Pﬁzer

and American Medical Systems.

2268

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Vol. 187, 2268-2274, June 2012

THE JOURNAL OF UROLOGY

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MERICAN

ROLOGICAL

SSOCIATION

DUCATION AND

ESEARCH

DOI:10.1016/j.juro.2012.01.032