Xiaflex® Plus Testosterone Treatment Pilot Study Protocol

In this open-label, six-month, pilot study of men with Peyronie's disease there will be one subject group consisting of 20 subjects. All subjects will receive Xiaflex® plus testosterone (T) treatment (Aveed®). Males included in the study must be 18-70 years old; have a history of PD for more than six months; and have at two serum total testosterone level less than 350 ng/dL within 30 days prior to enrollment. The primary objective of this pilot study is to determine whether testosterone therapy offers increased efficacy of Xiaflex® (collagenase clostridium histolyticum) in subjects undergoing treatment for Peyronie's disease.

Endpoints will include reduction in degree of curvature and response to the PDQ questionnaire. Secondary objectives will be to assess men for change in plaque size, quality of life parameters, and sexual function. Data collected from this pilot study will be analyzed and compared to historical data regarding treatment for PD using Xiaflex® only. This pilot study will establish preliminary evidence needed to continue more in-depth research regarding Xiaflex® with T therapy and serve as a means to evaluate feasibility of a full-scale study.

During this single-center pilot study, there will be one subject group consisting of men with Peyronie's disease and testosterone deficiency. Subject age range will be 18-70 years. Each subject will participate for approximately 6 months. All 20 subjects will receive Xiaflex® plus T treatment (Aveed®). Data collected from this pilot project will be analyzed and compared to historical data regarding treatment for PD using Xiaflex® only.

The eligibility criterion for 2 samples of total testosterone (\<350ng/dL) or free testosterone (1.5 ng/dL analog assay or 100pg/mL calculated free testosterone) was chosen with the aim of demonstrating what the effect of testosterone treatment is on men that fall into the low range. The remainder of the inclusion and exclusion criteria are designed to select subjects for whom protocol treatment is considered appropriate. All relevant medical and non-medical conditions will be taken into consideration when deciding whether this protocol is suitable for a particular subject.

Eligibility Criteria:
Inclusion Criteria:

1. Ability to read, write, and understand English
2. Age greater than or equal to 18
3. Age less than or equal to 70
4. Identification of acquired penile curvature of greater than 30 degrees and less than 90 degrees associated with palpable penile plaque on physical examination at screening
5. Screening total testosterone of less than 350 ng/dL, twice withine 30 days of treatment
6. Screening free testosterone of less than 1.5ng/dL (analog assay) or 100pg/mL (calculated)
7. Planning to initiate Xiaflex® injections at MHB
8. Willingness to initiate testosterone therapy
9. Willing to be followed at MHB for the next 3 months
10. Willing to provide informed consent for this study

Exclusion Criteria:

1. Prior history of treatment for PD that includes surgery
2. Prior treatment with oral therapy for PD unless at least stopped 2 weeks prior to signing the informed consent (e.g. Potaba, Vitamin E, colchicines)
3. Previous exposure to exogenous T, clomiphene citrate, or other Selective Estrogen Receptor Modulators, unless off therapy for at least 12 weeks
4. Presence of dense calcified plaque by ultrasound at screening
5. Hypersensitivity to testosterone, stearic acid, or polyvinylpyrolidone (the constituents of Aveed®)
6. Unwillingness to start testosterone therapy
7. Screening total testosterone of greater than 350 ng/dL
8. Screening free testosterone of more than 1.5ng/dL (analog assay) or 100pg/mL (calculated)
9. Unable to achieve adequate erection with penile injection to assess degree of curvature
10. Prior history of definitive treatment for prostate cancer, bladder cancer, or other pelvic malignancies including surgery, external beam radiation therapy, brachytherapy, cryotherapy
11. Prior history of prostate cancer, hematologic disorders, chronic liver disease including cirrhosis and hepatitis C, disorders affecting the immune system, including infection with human immunodeficiency virus, or psychiatric disorders including major depression, schizophrenia, bipolar disease
12. Prior history of cerebrovascular accident, history of deep venous thrombosis within the past 5 years or history of untreated or severe sleep apnea
13. Screening PSA more than 4.0 ng/mL, unless prostate cancer has been excluded to the Investigator's satisfaction
14. Incapable of giving informed consent or complying with the protocol