Phase I/II study to evaluate the efficacy and safety of bacterial collagenase administered in patients with Peyronie's Disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fidia Farmaceutici S.p.A.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Diseases [C] - Male Urogenital Diseases [C12]

Trial duration

22 Apr 2025 → ongoing

Decision date (initial)

2025-01-31

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Fidia Farmaceutici S.p.A.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Others, Efficacy, Safety

PHASE I PART - OBJECTIVE
Primary objective
To evaluate the safety and tolerability profile of each tested escalating dose as a single injection of V. alginolyticus collagenase injected into the plaque causing a deformity of the penis of patients with the Peyronie’s Disease in order to identify the Maximum Tolerated Dose.
PHASE II PART - OBJECTIVE
Primary objective
To assess the efficacy of the Maximum Tolerated Dose identified in Phase I part in terms of percentage improvement from baseline (screening assessment) in maximal penile curvature.

Secondary objectives 13

1. Secondary objectives – Phase I part: To conduct a responder analysis based on the subjects’ overall Global Assessment.
2. Secondary objectives – Phase I part: To evaluate change from baseline in penile discomfort following each tested escalating dose of V. alginolyticus collagenase in patients with the Peyronie’s Disease.
3. Secondary objectives – Phase I part: To evaluate blood exposure following administration of each tested escalating dose of V. alginolyticus collagenase.
4. Secondary objectives – Phase I part: To evaluate the immunogenic profile of each tested escalating dose of V. alginolyticus collagenase.
5. Secondary objectives - Phase II part: To conduct a responder analysis based on the subjects’ overall Global Assessment.
6. Secondary objectives - Phase II part: To evaluate change from baseline (screening assessment) in penile plaque consistency.
7. Secondary objectives - Phase II part: To evaluate change from baseline in total penile discomfort.
8. Secondary objectives - Phase II part: To conduct a composite responder analysis based on the change from baseline (screening assessment) in maximal penile curvature AND [(a reduction from baseline in penile discomfort of ≥1 (total score)) OR (a change from not being able to have a sexual intercourse at screening to having sexual intercourses during the study)].
9. Secondary objectives - Phase II part: To evaluate the change in penile length from baseline (screening assessment), through the performance of a penile physical examination, using basal and dynamic penile colour Doppler ultrasound with pharmacological stimulation.
10. Secondary objectives - Phase II part: To evaluate the change from baseline for the three domains (i.e., Erection, Ejaculation, Satisfaction scales) of the Male Sexual Health Questionnaire (MSHQ).
11. Secondary objectives - Phase II part: To evaluate the safety and tolerability profile of up to 3 injections for Dose regimen A (3 full dose injections at 4-week intervals) or up to 8 injections for Dose regimen B (4 treatment cycles – at 6-week intervals - of 2 half dose injections each, for a total of 8 injections) of V. alginolyticus collagenase.
12. Secondary objectives - Phase II part: To evaluate V. alginolyticus collagenase blood exposure 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.
13. Secondary objectives - Phase II part: To evaluate the immunogenic profile of V. alginolyticus collagenase at 29±2 days after the 3rd injection (Day 88±2) for Dose regimen A and at 42±2 days after the 4th and 8th injections (Days 85±2 and 169±2) for Dose regimen B.

Conditions and MedDRA coding

Peyronie’s Disease

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Informed Consent: signed written informed consent before inclusion in the study.
2. Sex and Age: men subjects ≥18 year of age.
3. 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.
4. 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.
5. Relationship: stable relationship with a partner for at least 3 months before screening and be willing to have sexual intercourse with that partner who does not have issues in guaranteeing compliance with the study (e.g. pregnancy, endometriosis, vulvodynia).
6. 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 18

1. Curvature: curvature deformity of <30° or >90° or ventral curvature from any cause, at the screening visit.
2. 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.
3. 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).
4. 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.
5. Hourglass Deformity: isolated hourglass deformity of the penis.
6. 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.
7. Peyronie’s Disease treatments: receiving or planning to undergo any other treatment of the Peyronie’s Disease during the study period and until the follow-up visit at 6 months, including but not limited to any surgery before 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 before the screening visit.
8. 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.
9. 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).
10. 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.
11. 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).
12. Pain perception: Limited or no pain perception, e.g. in the case of paraplegia or polyneuropathy (contraindication for vacuum assisted penile stretching).
13. Virology: known active hepatitis B or C, known immune deficiency disease (including human immunodeficiency virus [HIV]).
14. Medications: intake of tetracycline or their derivatives within 14 days before the screening.
15. Investigative drug studies: participation in the evaluation of any investigational product for 30 days before this study and until the follow-up visit at 6 months.
16. Blood donation: blood donations for 3 months before this study.
17. Sexual intercourse: subjects not engaging in sexual intercourse within 3 months prior to screening .
18. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. 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.
2. PHASE II PART - ENDPOINTS: Percentage of reduction in maximal penile curvature deformity as change from baseline (screening assessment) 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 angle will be measured using a goniometer device, after alprostadil induction of an erection.

Secondary endpoints 13

1. PHASE I PART - ENDPOINTS: Percentage of responders evaluated using the Global Assessment of Peyronie’s Disease 29±2 days after the injection of V. alginolyticus collagenase into the penile plaque.
2. 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.
3. 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.
4. 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.
5. PHASE II PART - ENDPOINTS: Percentage of responders based on the Global Assessment of Peyronie’s Disease assessed up to 29±2 days after the 3rd injection (Day 88±2) for Dose regimen A and up to 42±2 days after the 8th injection (last injection; Day 169±2) for Dose regimen B, of V. alginolyticus collagenase into the penile plaque.
6. PHASE II PART - ENDPOINTS: Penile plaque consistency scores, assessed at screening, 29±2 days after each injection and at the follow-up visit month 6±15 days for Dose regimen A and 42±2 days after each treatment cycle and at the follow-up visit month 6±15 days for Dose regimen B, of V. alginolyticus collagenase into the penile plaque.
7. 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.
8. PHASE II PART - ENDPOINTS: Proportion of composite responders defined as patients with a percentage reduction from baseline (screening assessment) 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 reduction from baseline in penile discomfort of ≥1 (total score)) OR (a change from not being able to have a sexual intercourse at screening to having sexual intercourses durin
9. PHASE II PART - ENDPOINTS: Change from baseline (screening assessment) in: • penile length (long side length, short side length), • circumference measured at the maximum curvature point, • maximal penile curvature measured by goniometry, • penile hemodynamic parameters [Peak systolic right and left, IR (Resistance Index), Rigidity]....
10. PHASE II PART - ENDPOINTS: Change from baseline for the three domains (Erection, Ejaculation and Satisfaction scales) 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.
11. 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].
12. 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.
13. 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.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fidia Farmaceutici S.p.A.

Sponsor organisation

Fidia Farmaceutici S.p.A.

Address

Via Ponte Della Fabbrica 3 A

City

Abano Terme

Postcode

35031

Country

Italy

Scientific contact point

Organisation

Fidia Farmaceutici S.p.A.

Contact name

Nicola Giordan

Public contact point

Organisation

Fidia Farmaceutici S.p.A.

Contact name

Nicola Giordan

Third parties 1

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 23 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications