Vibrio alginolyticus collagenase for Peyronie's disease

Inclusion criteria

• {"criterion_text":"- Informed Consent: signed written informed consent before inclusion in the study.\n- Sex and Age: men subjects ≥18 year of age.\n- Peyronie’s Disease: diagnosis of Peyronie’s Disease for at least 12 months, in the absence of pain (during erection) before the first dose of study drug, having a stable curvature deformity between 30° and 90° in the dorsal, lateral, or dorsal/lateral plane at screening (without any change in the deformity for at least 1 year), and an IIEF-5 score ≥17.\n- Full comprehension: ability to comprehend the full nature and purpose of the study, including possible risks and side effects; ability to co-operate with the Investigator and to comply with the requirements of the entire study including conduction of vacuum assisted penile stretching and manual modelling exercises.\n- Relationship: stable relationship with a partner for at least 3 months before screening and be willing to have sexual intercourse with that partner.\n- Contraception and fertility a. sexual abstinence for 15 days after injections in the Phase I part only b. sexual abstinence for 15 days (after each of the three injections for Dose regimen A and after each of the 4 treatment cycles for Dose regimen B) in Phase Part II and c. if having a female sexual partner of childbearing potential, must agree to use a male condom or d. must confirm to have a sterile sexual partner."}

Exclusion criteria

• {"criterion_text":"- Curvature: curvature deformity of <30° or >90° or ventral curvature from any cause, at the screening visit.\n- Allergy: ascertained or presumptive hypersensitivity to collagenase or investigational product excipients; history of anaphylaxis to drugs or allergic reactions in general, which the Investigator considers may affect the outcome of the study. Known hypersensitivity to alprostadil or to any of the excipients of alprostadil based medicinal product.\n- Diseases: significant history of cardiovascular, skin, endocrine or neurological diseases or of active sexually transmitted diseases or of any other medical condition which may interfere with the aim of the study (including clinically significant abnormal ECG).\n- Pain perception: Limited or no pain perception, e.g. in the case of paraplegia or polyneuropathy (contraindication for vacuum assisted penile stretching).\n- Virology: known active hepatitis B or C, known immune deficiency disease (including human immunodeficiency virus [HIV]).\n- Medications: intake of tetracycline or their derivatives within 14 days before the screening.\n- Investigative drug studies: participation in the evaluation of any investigational product for 30 days before this study.\n- Blood donation: blood donations for 3 months before this study.\n- Sexual intercourse: subjects not engaging in sexual intercourse within 3 months prior to screening .\n- No comprehension: INABILITY to comprehend the full nature and purpose of the study, possible risks and side effects; INABILITY to co-operate with the Investigator and to comply with the requirements of the entire study including vacuum assisted penile stretching and home modelling exercises.\n- Underlying penis pathology: any condition affecting the penis, such as chordee in the presence or absence of hypospadias, thrombosis of the dorsal penile artery, infiltration by a benign or malignant mass or an infectious agent, significant erectile dysfunction that had failed to respond to oral treatment with phosphodiesterase type 5 inhibitors, priapism.\n- Curvature Measurement: failing erection that, in the opinion of the Investigator, is insufficient to accurately measure the subject’s penile deformity after administration of a prostaglandin E1-like drug (alprostadil).\n- Calcified Plaque: calcified plaque, as evident by appropriate penile ultrasound preventing a proper injection of the study treatment, with the exclusion of a non-contiguous stippling of calcium, provided that calcium deposit does not interfere with the injection of collagenase into the plaque; Peyronie’s plaques that involve the penile urethra, due to potential risk to this structure.\n- Hourglass Deformity: isolated hourglass deformity of the penis.\n- Proximal Plaque: plaque causing curvature of the penis located proximal to the base of the penis, so that the injection of the local anaesthetic could interfere with the injection of collagenase into the plaque.\n- Peyronie’s Disease treatments: receiving or planning to undergo any other treatment of the Peyronie’s Disease during the study period, including but not limited to any surgery before and during the study, oral/topical agents within 3 months, intralesional medical therapies within 3 months, extracorporeal shock wave therapy within 6 months, use of mechanical devices within 2 weeks.\n- Baseline Hemodynamic: a penile duplex Doppler ultrasound evaluation at screening that shows compromised penile hemodynamic that, in the opinion of the Investigator, is clinically significant.\n- Bleeding and anticoagulants: history of bleeding, coagulation disorders, anticoagulant or antiaggregant therapy within 7 days of the screening with the exception of low daily intake of acetylsalicylic acid (100 mg/die)."}

Primary endpoints

• {"endpoint_text":"- PHASE I PART - ENDPOINTS: Overall safety and tolerability profile of each tested escalating dose of V. alginolyticus collagenase in order to identify the Maximum Tolerated Dose.","definition_or_measurement_approach":"Evaluate overall safety and tolerability of each escalating single injection dose to identify the Maximum Tolerated Dose (MTD). Specific safety measurements not further detailed in the primary endpoint text."}
• {"endpoint_text":"- PHASE II PART - ENDPOINTS: Percentage of reduction in maximal penile curvature deformity as change from baseline at 29±2 days after the 3rd injection (Day 88±2) for Dose regimen A and 42±2 days after the 8th injection (Day 169±2) for Dose regimen B. Penile curvature will be measured using a goniometer protractor device, after alprostadil induction of an erection.","definition_or_measurement_approach":"Maximal penile curvature change from baseline measured by goniometer protractor device after alprostadil-induced erection at specified post-injection timepoints (Day 88±2 for regimen A; Day 169±2 for regimen B)."}

Secondary endpoints

• {"endpoint_text":"- PHASE I PART - ENDPOINTS: Overall change in symptoms and effects of Peyronie’s Disease on patients’ lives, evaluated using the Global Assessment of Peyronie’s Disease 29±2 days after the injection of V. alginolyticus collagenase into the penile plaque.","definition_or_measurement_approach":"Global Assessment of Peyronie’s Disease assessed 29±2 days post-injection."}
• {"endpoint_text":"- PHASE I PART - ENDPOINTS: Evaluation of the change from baseline in total penile discomfort assessed 29±2 days after the injection of V. alginolyticus collagenase into the penile plaque.","definition_or_measurement_approach":"Change from baseline in total penile discomfort assessed 29±2 days post-injection."}
• {"endpoint_text":"- PHASE I PART - ENDPOINTS: Blood exposure, evaluated as serum levels of collagenase at pre-dose and at 0.5, 1, 2 and 4 h post-dose after each tested escalating dose of V. alginolyticus collagenase.","definition_or_measurement_approach":"Pharmacokinetic sampling: serum levels at pre-dose and 0.5, 1, 2 and 4 hours post-dose after each tested dose."}
• {"endpoint_text":"- PHASE I PART - ENDPOINTS: Immunogenicity, evaluated through assay of serum anti-drug antibodies (ADA) and neutralising antibodies (nAb) at pre-dose and at 29±2 days after each tested escalating dose of V. alginolyticus.","definition_or_measurement_approach":"Immunogenicity assessment by ADA and nAb assays at pre-dose and 29±2 days post-dose."}
• {"endpoint_text":"- PHASE II PART - ENDPOINTS: Overall change in symptoms and effects of Peyronie’s Disease on patients’ lives, using the Global Assessment of Peyronie’s Disease assessed 29±2 days after the 3rd injection (Day 88±2) for Dose regimen A and 42±2 days after the 8th injection (last injection; Day 169±2) for Dose regimen B, of V. alginolyticus collagenase into the penile plaque.","definition_or_measurement_approach":"Global Assessment of Peyronie’s Disease at specified timepoints after injections (Day 88±2 for A; Day 169±2 for B)."}
• {"endpoint_text":"- PHASE II PART - ENDPOINTS: Overall Satisfaction Domain of the IIEF-5 scores, assessed 29±2 days after the 3rd injection (Day 88±2) for Dose regimen A and 42±2 days after the 8th injection (last injection; Day 169±2) for Dose regimen B, of V. alginolyticus collagenase into the penile plaque, will be summarised as proportion of subjects for each score.","definition_or_measurement_approach":"IIEF-5 Overall Satisfaction Domain scores summarised as proportions at Day 88±2 (A) and Day 169±2 (B)."}
• {"endpoint_text":"- PHASE II PART - ENDPOINTS: Penile plaque consistency scores, assessed 29±2 days after the 3rd injection (Day 88±2) for Dose regimen A up to the follow-up visit month 6±15 days and 42±2 days after the 8th injection (last injection; Day 169±2) up to the follow-up visit month 6±15 days for Dose regimen B, of V. alginolyticus collagenase into the penile plaque, will be summarised as proportion of subjects for each score.","definition_or_measurement_approach":"Penile plaque consistency scores assessed at specified post-injection timepoints and up to month 6±15 days follow-up, summarised as proportions."}
• {"endpoint_text":"- PHASE II PART - ENDPOINTS: Evaluation of the change from baseline in total penile discomfort assessed 29±2 days after the 3rd injection (Day 88±2) for Dose regimen A and 42±2 days after the 8th injection (last injection; Day 169±2) for Dose regimen B of V. alginolyticus collagenase into the penile plaque.","definition_or_measurement_approach":"Change from baseline in total penile discomfort at specified timepoints (Day 88±2 for A; Day 169±2 for B)."}
• {"endpoint_text":"- PHASE II PART - ENDPOINTS: Proportion of composite responders defined as patients with a percentage reduction from baseline 29±2 days after the 3rd injection (Day 88±2) for Dose regimen A and 42±2 days after the 8th injection (Day 169±2) for Dose regimen B in maximal penile curvature of ≥20% and a change from not being able to have a sexual intercourse at screening to having sexual intercourses during the study.","definition_or_measurement_approach":"Composite responder analysis: ≥20% reduction in maximal curvature at specified timepoints combined with change from inability to have penetrative intercourse at screening to having intercourse during study."}
• {"endpoint_text":"- PHASE II PART - ENDPOINTS: Change from baseline in penile length (long side length, short side length), circumference measured at the maximum curvature point, maximal penile curvature measured by goniometry and with respect to penile hemodynamic parameters assessed 29±2 days after the 3rd injection (Day 88±2) for Dose regimen A and 42±2 days after the 8th injection (last injection; Day 169±2) for Dose regimen B, of V. alginolyticus collagenase into the penile plaque, during penile physical exam.","definition_or_measurement_approach":"Physical exam measures: penile lengths, circumference at max curvature, maximal curvature by goniometry and hemodynamic parameters at specified timepoints."}
• {"endpoint_text":"- PHASE II PART - ENDPOINTS: Change from baseline for all items of the MSHQ assessed 29±2 days after the 3rd injection (Day 88±2) for Dose regimen A and 42±2 days after the 8th injection (last injection; Day 169±2) for Dose regimen B, of V. alginolyticus collagenase into the penile plaque.","definition_or_measurement_approach":"MSHQ item changes from baseline assessed at specified timepoints."}
• {"endpoint_text":"- PHASE II PART - ENDPOINTS: Overall safety and tolerability profile following each injection of V. alginolyticus collagenase [Treatment-Emergent Adverse Events; vital signs (blood pressure, pulse rate), physical examinations; laboratory tests; ECGs].","definition_or_measurement_approach":"Safety assessments including TEAEs, vital signs, physical exams, labs and ECGs after each injection."}
• {"endpoint_text":"- PHASE II PART - ENDPOINTS: Blood exposure, evaluated as serum levels of collagenase at pre-dose and 0.5, 1, 2 and 4 h post-dose after each injection (Days 1, 30±2 and 59±2) for Dose regimen A and after the second injection of each treatment cycle (24-72 h after the first injection of each treatment cycle) for Dose regimen B of V. alginolyticus collagenase.","definition_or_measurement_approach":"PK sampling schedule: pre-dose and 0.5,1,2,4 h post-dose at specified injection days for regimens A and B."}
• {"endpoint_text":"- PHASE II PART - ENDPOINTS: Immunogenicity, evaluated through assay of serum anti-drug antibodies (ADA) and neutralising antibodies (nAb) in all subjects, at pre-dose and at 29±2 days after last injection (Day 88±2) for Dose regimen A, and at 42±2 days after both the 4th and 8th injections (Days 85±2 and 169±2) for Dose regimen B.","definition_or_measurement_approach":"ADA and nAb assays at pre-dose and specified post-injection timepoints for immunogenicity evaluation."}

Italy

Earliest CTIS Part Ii Submission Date

08-01-2025

Latest Decision Or Authorization Date

30-04-2025

Processing Time Days

112

Number Of Sites

2

Number Of Participants

100

Primary sponsor

Full Name

Fidia Farmaceutici S.p.A.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Italy

Contract research organisations

Name

Cross Research S.A.

Responsibilities

Sponsor duties codes: 1,10,11,12,5,6; contact elena.gander@croalliance.com; phone 0041916300510

Third parties

• {"country":"Switzerland","full_name":"Cross Research S.A.","duties_or_roles":"sponsor duties codes: 1,10,11,12,5,6","organisation_type":"Pharmaceutical company"}