Efficacy Of Collagenase Clostridium Histolyticum Research Articles

Efficacy and safety of collagenase clostridium histolyticum for Dupuytren disease nodules: a randomized controlled trial

BackgroundTo determine the safety and efficacy of collagenase clostridium histolyticum (CCH) injection for the treatment of palmar Dupuytren disease nodules.MethodsIn this 8-week, double-blind trial, palpable palmar nodules on one hand of adults with Dupuytren disease were selected for treatment. Patients were randomly assigned using an interactive web response system to receive a dose of 0.25 mg, 0.40 mg, or 0.60 mg (1:1:1 ratio) and then allocated to active treatment (CCH) or placebo (4:1 ratio). All patients and investigators were blinded to treatment. One injection was made in the selected nodule on Day 1. Caliper measurements of nodule length and width were performed at screening and at Weeks 4 and 8. Investigator-reported nodular consistency and hardness were evaluated at baseline and Weeks 1, 4, and 8. Investigator-rated patient improvement (1 [very much improved] to 7 [very much worse]) and patient satisfaction were assessed at study end.ResultsIn the efficacy population (n = 74), percentage changes in area were significantly greater with CCH 0.40 mg (−80.1%, P = 0.0002) and CCH 0.60 mg (−78.2%, P = 0.0003), but not CCH 0.25 mg (−58.3%, P = 0.079), versus placebo (−42.2%) at post-treatment Week 8. Mean change in nodular consistency and hardness were significantly improved with CCH versus placebo at Weeks 4 and 8 (P ≤ 0.0139 for all). At Week 8, investigator global assessment of improvement was significantly greater with CCH 0.40 mg and 0.60 mg (P ≤ 0.0014) but not statistically significant with CCH 0.25 mg versus placebo (P = 0.13). Most patients were “very satisfied” or “quite satisfied” with CCH 0.40 mg and 0.60 mg. Contusion/bruising (50.0% to 59.1%) was the most common adverse event with CCH treatment.ConclusionIn patients with Dupuytren disease, a single CCH injection significantly improved palmar nodule size and hardness. The safety of CCH was similar to that observed previously in patients with Dupuytren contracture.Trial registrationClinicalTrials.gov identifier: NCT02193828. Date of trial registration: July 2, 2014 to December 5, 2014

Injectable Collagenase Versus Percutaneous Needle Fasciotomy for Dupuytren Contracture in Proximal Interphalangeal Joints: A Randomized Controlled Trial

Collagenase Clostridium histolyticum (CCH) injection was introduced commercially as a treatment for Dupuytren contracture following initial phase-3 investigations in 2009 with promising results. However, the efficacy of CCH has not been prospectively investigated in a direct comparison to other active treatments of Dupuytren contracture with more than 1-year follow-up, despite a wide and increasing clinical use. In this prospective, independent, open-label, randomized controlled trial, (Clinicaltrials.gov; NCT 01538017), percutaneous needle fasciotomy (PNF) was directly compared with CCH.Fifty patients with primary isolated proximal interphalangeal joint Dupuytren contractures were enrolled and followed for 2 years. The primary outcome was clinical improvement defined as a reduction in contracture by 50% or more relative to baseline. Secondary outcomes included change in contracture, recurrence, adverse events, complications, and Disabilities of the Arm, Shoulder, and Hand questionnaire score. Clinical improvement at 2 years was maintained in 7% of CCH patients (2 of 29) and 29% of PNF patients (6 of 21). Collagenase Clostridium histolyticum led to more, mainly transient, complications, in 93% of patients versus 24% of the patients treated with PNF. No other differences were observed. This study provides evidence that CCH is not superior to PNF in the treatment of isolated proximal interphalangeal joint Dupuytren contracture regarding clinical outcome, and it led to more complications than PNF. Therapeutic I.

Collagenase Clostridium Histolyticum in the Treatment of Urologic Disease: Current and Future Impact.

Peyronie's disease (PD) is a connective tissue disorder resulting in the abnormal accumulation of type I to III collagen, fibrin, and disorganized elastic fibers in the tunica albuginea of the penis. Many medical and non-pharmacologic modalities have been used in the treatment of PD; however, these approaches have proved largely ineffective, with surgery being the only definitive treatment. Intralesional injection of collagenase Clostridium histolyticum (CCH) has recently become the gold standard for minimally invasive treatment of PD, and studies have suggested the role of CCH could expand to the treatment of other urologic conditions such as urethral stricture disease. To provide an update on available data on the use of CCH in the treatment of PD and other urologic conditions. Comprehensive review of recent clinical trials and invivo studies that examined the safety and efficacy of CCH in urologic disease. Assessing the efficacy of CCH in the management of PD as determined by improvement in the severity of penile fibrosis, curvature deformity, and pain. Several well-designed clinical trials have demonstrated the efficacy and tolerability of CCH in the treatment of PD. CCH has demonstrated significant decreases in penile curvature and plaque consistency and improvements in patient satisfaction. Treatment durability and long-term adverse effects are still being assessed; however, outcomes of PD management with CCH continue to replicate the results obtained during the IMPRESS clinical trials. Preliminary studies support the premise that CCH can modify disease progression in patients with acute-phase PD. Furthermore, one invivo study showed that CCH also could be applied to urethral stricture disease without serious adverse complications. CCH continues to be the mainstay for non-surgical management of stable-phase PD. However, its role in the treatment of acute-phase PD, PD with ventral plaques, and urethral stricture disease could expand in the coming years. Gabrielson AT, Spitz JT, Hellstrom WJG. Collagenase Clostridium Histolyticum in the Treatment of Urologic Disease: Current and Future Impact. Sex Med Rev 2018;6:143-156.

MP56-04 SAFETY AND EFFECTIVENESS OF COLLAGENASE CLOSTRIDIUM HISTOLYTICUM IN THE TREATMENT OF PEYRONIE'S DISEASE USING A NEW SHORTENED PROTOCOL

You have accessJournal of UrologySexual Function/Dysfunction: Peyronie’s Disease II1 Apr 2017MP56-04 SAFETY AND EFFECTIVENESS OF COLLAGENASE CLOSTRIDIUM HISTOLYTICUM IN THE TREATMENT OF PEYRONIE'S DISEASE USING A NEW SHORTENED PROTOCOL Amr Abdel Raheem, Marco Capece, Ayo Kaljaiye, Amr Mobasher, Giulio Garaffa, Nim Christopher, and David Ralph Amr Abdel RaheemAmr Abdel Raheem More articles by this author , Marco CapeceMarco Capece More articles by this author , Ayo KaljaiyeAyo Kaljaiye More articles by this author , Amr MobasherAmr Mobasher More articles by this author , Giulio GaraffaGiulio Garaffa More articles by this author , Nim ChristopherNim Christopher More articles by this author , and David RalphDavid Ralph More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.1757AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Collagenase clostridium histolyticum (CCH)is the only licensed product for the treatment of Peyronie's disease (PD). The clinical safety and efficacy of CCH in PD was shown in two large clinical trials; IMPRESS I & II. The aim of this study is to evaluate the efficacy and safety of CCH in the treatment of PD using a new modified treatment protocol which aims at reducing the number of injections needed and reducing patient visits, thus reducing the cost and duration of treatment. METHODS A prospective study of 50 patients with PD who are having treatment with CCH at a single centre using a new modified protocol. Patients with active disease, complete plaque calcification or ventral curvature were excluded. The angle of curvature assessment after an intra-cavernosal injection of PGE1, IIEF and Peyronie's disease questionnaire (PDQ) were performed at baseline and at week 12. The global assessment of PD questionnaire was performed at week 12. Under a penile block of 10ml of lignocaine 1%, a total of 3 intra-lesional injections of CCH (0.9mg) were given at 4 weekly intervals using a new modified injection technique. CCH was injected in the plaque along 3 lines separated by 2mm at the apex of the curvature with the penis in the flaccid state. Six patients requested an additional 3 injections to have a total of 6 injections. In between injections patients used a combination of home modelling, stretching and a vacuum device on a daily basis in order to mechanically stretch the plaque. Investigator modelling was not performed. RESULTS So far 46 patients have completed treatment; all had 3 injections. At baseline, the mean penile curvature was 53.8°(30°-90°). Overall, 44 patients (95.6%) had an improvement in curvature with a mean value of 17.08° (0°-40°) or 30.8% from baseline (0-57%) after 3 injections. The end mean curvature for all patients after 3 injections was 37° (12°- 75°; p≤ 0.001). There was a statistically significant improvement in each of the IIEF questionnaire domains, all 3 PDQ domains and the global assessment of PD questionnaire. The 6 patients who had 3 more injections continued to have additional curvature improvement, mean 19.8° (0°-40°). CCH was well tolerated by all patients with only mild and transient local side effects. The results of this study with only 3 CCH injections are comparable to those of the clinical trials using 8 CCH injections. With the new protocol, only 4 patient visits are needed including assessments versus 14 visits as per trial protocol. CONCLUSIONS The new shortened protocol for CCH in PD is safe, effective and cost efficient. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e756 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Amr Abdel Raheem More articles by this author Marco Capece More articles by this author Ayo Kaljaiye More articles by this author Amr Mobasher More articles by this author Giulio Garaffa More articles by this author Nim Christopher More articles by this author David Ralph More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

006 Safety and Efficacy of Collagenase Clostridium Histolyticum in the Treatment of Active Phase Peyronie's Disease

006 Safety and Efficacy of Collagenase Clostridium Histolyticum in the Treatment of Active Phase Peyronie's Disease

003 The Safety and Efficacy of Collagenase Clostridium Histolyticum (CCH) in Combination With Vacuum Therapy for the Treatment of Peyronie's Disease

003 The Safety and Efficacy of Collagenase Clostridium Histolyticum (CCH) in Combination With Vacuum Therapy for the Treatment of Peyronie's Disease

PD22-04 EFFECT OF TIME BETWEEN FIRST AND SECOND INJECTION OF COLLAGENASE CLOSTRIDIUM HISTOLYTICUM ON PENILE CURVATURE DEFORMITY DURING THE FIRST TREATMENT CYCLE OF MEN WITH PEYRONIE’S DISEASE

You have accessJournal of UrologySexual Function/Dysfunction/Andrology: Peyronie's Disease1 Apr 2014PD22-04 EFFECT OF TIME BETWEEN FIRST AND SECOND INJECTION OF COLLAGENASE CLOSTRIDIUM HISTOLYTICUM ON PENILE CURVATURE DEFORMITY DURING THE FIRST TREATMENT CYCLE OF MEN WITH PEYRONIE’S DISEASE Larry I. Lipshultz, James P. Tursi, Gregory J. Kaufman, Genzhou Liu, and Hossein Sadeghi-Nejad Larry I. LipshultzLarry I. Lipshultz More articles by this author , James P. TursiJames P. Tursi More articles by this author , Gregory J. KaufmanGregory J. Kaufman More articles by this author , Genzhou LiuGenzhou Liu More articles by this author , and Hossein Sadeghi-NejadHossein Sadeghi-Nejad More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.1855AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Plaque formation of mainly disordered collagen within the tunica albuginea leads to the characteristic penile curvature deformity (PCD) of Peyronie's disease (PD). Collagenase clostridium histolyticum (CCH) is an intralesional, noninvasive therapy that improved certain physical and psychological aspects of PD in phase 2 and 3 studies. Because variable times between injections per cycle were allowed (24-72 h), we assessed the effect of time between the first and second injection of CCH within the first treatment cycle (Cycle 1) on PCD. METHODS IMPRESS I/II were identical phase 3, randomized, placebo-control studies of men with PD (n=832). Each treatment cycle included 2 injections of CCH 0.58 mg or placebo given 24-72 h apart, with plaque modeling within 24-72 h after the second injection. Men were stratified by time period between injections in Cycle 1 by Day 1, 2, or 3+ groups. The mean percent improvement in PCD and occurrence of adverse events (AEs) from baseline to Week 6 were reported. RESULTS 548 and 280 men in the CCH and placebo groups, respectively, who received 2 injections in Cycle 1 were included in this analysis. The mean percent improvement in PCD from baseline to Week 6 in the CCH group by time period between injections of 1, 2, or 3+ days was 12.1±19.3%, 13.7±20.5%, and 12.2±21.9%, vs 5.8±15.2%, 4.8±21.1%, and 12.4±18.2% in the placebo group (Figure). The most common treatment-related AEs reported during Cycle 1 were penile hematoma, penile swelling, and penile pain (Table). All AEs occurred at the site of injection and were mild or moderate in severity. No treatment-related serious AEs were reported during Cycle 1. CONCLUSIONS Administration of the second injection of CCH 1, 2, or 3+ days after the first injection during Cycle 1 did not impact the safety or efficacy of CCH in improving PCD at Week 6. This data supports flexibility in planning CCH treatment cycles without loss of efficacy. Table. Common (>5%) Treatment-Related AEs Occurring During Cycle 1 by Number of Days Between First and Second Injections of Cycle 1 Preferred Term, n (%) 1 Day (n=198) 2 Days (n=243) 3+ Days (n=107) Penile hematomaa 84 (42.4) 102 (42.0) 43 (40.2) Penile swelling 38 (19.2) 41 (16.9) 19 (17.8) Penile pain 35 (17.7) 45 (18.5) 28 (26.2) Injection site pain 21 (10.6) 18 (7.4) 5 (4.7) Injection site hematoma 21 (10.6) 21 (8.6) 8 (7.5) Penile hemorrhageb 16 (8.1) 28 (11.5) 17 (15.9) Ecchymosis 1 (0.5) 4 (1.6) 8 (7.5) Contusion 15 (7.6) 8 (3.3) 5 (4.7) Injection site swelling 13 (6.6) 12 (4.9) 2 (1.9) Penile edema 12 (6.1) 21 (8.6) 10 (9.3) a92.1% of treatment-related AEs of penile hematoma had the verbatim term ″penile bruising.″ b100% of treatment-related AEs of penile hemorrhage had the verbatim term ″penile ecchymosis.″ © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e673 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Larry I. Lipshultz More articles by this author James P. Tursi More articles by this author Gregory J. Kaufman More articles by this author Genzhou Liu More articles by this author Hossein Sadeghi-Nejad More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

1656 CLINICAL EVALUATION OF TREATMENT OF PEYRONIE'S DISEASE WITH COLLAGENASE CLOSTRIDIUM HISTOLYTICUM: ANALYSIS OF PENILE CURVATURE DEFORMITY BY DURATION OF DISEASE AND PLAQUE CALCIFICATION

Introduction and Objective: Three phase 3 studies have been conducted to examine the safety and efficacy of collagenase clostridium histolyticum (CCH) in subjects with Peyronie’s disease (PD). The effect of CCH on change in penile curvature deformity from baseline to end of study was analyzed by the subjects’ duration of disease or degree of plaque calcification. Methods: All subjects within the phase 3 studies (2 randomized, doubleblind, placebo-controlled; 1 open-label [interim data]) and who were treated with CCH received up to 8 injections of CCH (0.58 mg) with 2 injections per cycle separated by about 24 to 72 hours, with the second injection followed 24 to 72 hours later by plaque modeling. A maximum of up to 4 cycles each was allowed, with each cycle separated by a 6-week interval. Penile x-ray or ultrasound findings were used to determine the degree of plaque calcification (no calcification, non-contiguous stippling, and contiguous calcification that did not interfere with the injection). Results: CCH-treated subjects (N=775) were stratified by duration of disease: 1-2 years (n=280), >2 to ≤4 years (n=266), and >4 years (n=229). Change in mean curvature deformity by duration of disease is shown in Figure 1 and by degree of plaque calcification in Figure 2. Duration of disease had no relationship to the degree of calcification (no calcification=3.8 years, non-contiguous stippling=4.2 years, and contiguous calcification that did not interfere with the injection=3.3 years). Conclusions: Treatment with CCH resulted in improvements in curvature deformity regardless of duration of disease or level of plaque calcification; although small differences were noted within the subgroups, they are not expected to be clinically meaningful. The observation that the duration of disease had no relationship with the degree of calcification in this population warrants further exploration. Presented at the American Urological Association’s 2013 Annual Meeting, May 4 8, 2013, San Diego, CA. • CCH is approved for treatment of adults with Dupuytren’s contracture (DC) with a palpable cord.7 Two identical, randomized, doubleblind, placebo-controlled, pivotal, phase 3 clinical trials (IMPRESS I and II) were conducted to investigate the use of CCH (followed by a modeling procedure) in subjects with PD – A recently published analysis of this data showed that CCHtreated subjects had a significantly greater improvement in penile curvature deformity compared with placebo subjects (34% vs 18.2%; P<0.0001)8 – Significant improvements in the PD symptom bother domain score for CCH-treated subjects compared with placebo subjects were also observed (-2.8±3.8 vs -1.8±3.5; P=0.0037)

1657 SUBGROUP ANALYSIS OF CURVATURE DEFORMITY SEVERITY AND SYMPTOM BOTHER IMPROVEMENT IN PATIENTS WITH PEYRONIE'S DISEASE BEING TREATED WITH COLLAGENASE CLOSTRIDIUM HISTOLYTICUM IN CLINICAL STUDIES

INTRODUCTION AND OBJECTIVES: The Investigation for Maximal Peyronie’s Reduction Efficacy and Safety Studies (IMPRESS) I and II examined the clinical efficacy of collagenase clostridium histolyticum (CCH) in subjects with Peyronie’s disease (PD). The effect of CCH on penile curvature deformity severity and the PD symptom bother score using the Peyronie’s disease questionnaire (PDQ) was evaluated in different patient populations. METHODS: Subjects 18 years of age with PD symptoms for 12 months and penile curvature deformity of 30° to 90° were enrolled in the identical randomized, double-blind, placebo-controlled, phase 3 IMPRESS studies. Subjects received up to 8 injections of 0.58 mg CCH, two injections per cycle separated by approximately 24 to 72 hours, with the second injection followed 24-72 hours later by plaque modeling. Each cycle was separated by a period of 6 weeks. A subgroup analysis was performed to analyze the effect of age, concomitant diabetes mellitus (DM), and previous penile trauma on outcomes following treatment at Week 52. RESULTS: A total of 401 CCH-treated subjects combined from IMPRESS I and II with at least one penile curvature measurement and PDQ response recorded were included. Outcomes by age are shown in Table 1. Patients with DM treated with CCH experienced a mean improvement in penile curvature of 17.2° (34.4%) versus 17.0° (34.0%) in those without DM. The mean improvement in PD symptom bother for the two groups was 2.7 and 2.9, respectively. Subjects with or without a history of penile trauma treated with CCH experienced a mean improvement in penile curvature of 17.9° (35.1%) vs 16.7° (33.7%), respectively. The improvement in PD symptom bother was 3.0 in subjects with a history of penile trauma and 2.8 in those without. CONCLUSIONS: Improvements in penile curvature and PD symptom bother score were realized regardless of age, concomitant diabetes, or history of penile trauma. Overall, CCH improved the psychosexual and physical symptoms of PD in diverse patient populations.