VIBRIO ALGINOLYTICUS COLLAGENASE for Dupuytren's contracture

Inclusion criteria

• {"criterion_text":"-Informed consent: signed written informed consent before inclusion in the study"}
• {"criterion_text":"-Sex and Age: men/women, ≥18 year old inclusive"}
• {"criterion_text":"-Dupuytren contracture: diagnosis of Dupuytren contracture with a fixed flexion deformity ≥20° and ≤100°, if in a MP joint, or ≥20° and ≤80°, if in a PIP joint, of at least one finger, other than the thumb, caused by a palpable cord that, according to the investigator’s judgement, could benefit from treatment with collagenase"}
• {"criterion_text":"-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"}
• {"criterion_text":"-Contraception and fertility (women only): women of child-bearing potential must be using at least one of the following reliable methods of contraception: a. Hormonal oral, implantable, transdermal, or injectable contraceptives for at least 2 months before the screening visit b. A non-hormonal intrauterine device or female condom with spermicide or contraceptive sponge with spermicide or diaphragm with spermicide or cervical cap with spermicide for at least 2 months before the screening visit c. A male sexual partner who agrees to use a male condom with spermicide d. A sterile sexual partner e. Sexual abstinence Female participants of non-child-bearing potential or in post-menopausal status for at least 1 year will be admitted. For all women of child-bearing potential, pregnancy test result must be negative at screening and Day 1 predose."}

Exclusion criteria

• {"criterion_text":"-Previous Dupuytren contracture treatments: a. surgical treatments: patients who underwent fasciectomy or surgical fasciotomy in the selected primary hand, and patients treated with needle aponeurotomy (percutaneous needle fasciotomy) in the selected joint; b. pharmacological treatments: patients previously treated with any pharmacological treatment of Dupuytren’s contracture in the selected primary hand within 90 days prior to screening. Additionally, patients previously treated with C. histolyticum in the same finger of the selected joint, or with V. alginolyticus collagenase, regardless of the hand or joint treated. However, patients enrolled in a placebo study arm in previous clinical trials of V. alginolyticus collagenase may be included"}
• {"criterion_text":"-Hand disorders: chronic muscular, neurological or neuromuscular disorders affecting hands which may interfere with the clinical assessment"}
• {"criterion_text":"-Bleeding and anticoagulants: history of bleeding, coagulopathies including any disorder that could increase the patient’s tendency to bruising or haematoma or bleeding, anticoagulant or antiaggregant therapy within 7 days of the screening with the exception of daily intake of ≤150 mg of acetylsalicylic acid"}
• {"criterion_text":"-Allergy: ascertained or presumptive hypersensitivity to collagenase; history of anaphylaxis to drugs or allergic reactions in general, which the investigator considers may affect the outcome of the study"}
• {"criterion_text":"-Diseases: significant history of cardiovascular, skin, endocrine or neurological diseases that affected the hands or of any other medical condition which may interfere with the aim of the study (including clinically significant abnormal ECG)"}
• {"criterion_text":"-Medications: intake of tetracycline derivatives within 14 days before the screening"}
• {"criterion_text":"-Investigative drug studies: previous participation in any clinical studies within 30 days before the screening visit"}
• {"criterion_text":"-Blood donation: blood donations for 3 months before this study"}
• {"criterion_text":"-Pregnancy (women of child-bearing potential only): positive or missing pregnancy test at screening or Day 1, pregnant or lactating women"}

Primary endpoints

• {"endpoint_text":"-Primary endpoint in the Phase I part: Overall safety profile of each escalating dose of V. alginolyticus collagenase in order to identify the maximum tolerated dose in the absence of limiting toxicity as defined for the dose escalating process.","definition_or_measurement_approach":"Safety and tolerability assessment of each escalating dose to identify maximum tolerated dose; assessed by adverse events and dose-limiting toxicities per dose-escalation rules (as defined in protocol)."}
• {"endpoint_text":"-Primary endpoint in the Phase II part: -Proportion of patients who achieve clinical success defined as a reduction in contracture to ≤5° in 30±3 days after the last injection of V. alginolyticus collagenase into the cord in the affected primary joint as measured by passive angle of finger extension as compared to matching placebo In the evaluation of each endpoint, MP and PIP joints will be evaluated cumulatively and separated.","definition_or_measurement_approach":"Proportion achieving clinical success defined as reduction in contracture to ≤5° measured by passive angle of finger extension at 30±3 days after last injection; MP and PIP joints evaluated cumulatively and separately; compared to matching placebo."}

Secondary endpoints

• {"endpoint_text":"-Secondary endpoints in the Phase I part: - Proportion of patients who achieve a reduction in contracture to ≤5° (clinical success) as measured by passive finger goniometry 30±3 days after one injection of each tested ascending dose","definition_or_measurement_approach":"Proportion achieving ≤5° contracture measured by passive finger goniometry at 30±3 days after one injection of each tested ascending dose."}
• {"endpoint_text":"-Proportion of patients who have ≥50% reduction from baseline in contracture (clinical improvement) as measured by passive finger goniometry 30±3 days after one injection of each tested ascending dose","definition_or_measurement_approach":"Proportion with ≥50% reduction from baseline in contracture measured by passive finger goniometry at 30±3 days after one injection."}
• {"endpoint_text":"-Percentage change from baseline in contracture degree as measured by passive finger goniometry 30±3 days after one injection of each tested single ascending dose","definition_or_measurement_approach":"Percent change from baseline in contracture degree measured by passive finger goniometry at 30±3 days after one injection."}
• {"endpoint_text":"-Percentage change from baseline in passive finger flexion 30±3 days after one injection of each tested dose","definition_or_measurement_approach":"Percent change from baseline in passive finger flexion at 30±3 days after one injection."}
• {"endpoint_text":"-Change from baseline in the range of motion after injection of each tested single ascending dose","definition_or_measurement_approach":"Change from baseline in range of motion after injection of each tested single ascending dose (timing per protocol assessments)."}
• {"endpoint_text":"-Secondary endpoints in the Phase II part:  Proportion of patients who achieve a clinical improvement defined as a reduction from baseline in contracture by ≥50% in 30±3 days after the last injection of V. alginolyticus collagenase into the cord in the affected primary joint as measured by passive angle of finger extension as compared to matching placebo","definition_or_measurement_approach":"Proportion with ≥50% reduction from baseline in contracture measured by passive angle of finger extension at 30±3 days after last injection compared with matching placebo."}
• {"endpoint_text":"-Mean number of injections of V. alginolyticus collagenase into the affected cord in the primary joint (MP or PIP) necessary to achieve clinical success as compared to matching placebo","definition_or_measurement_approach":"Mean number of injections required to achieve clinical success compared between active and placebo arms."}
• {"endpoint_text":"-Median time (in days) to achieve and maintain clinical success after the last injection of V. alginolyticus collagenase into the affected cord in the primary joint (MP or PIP) as compared to matching placebo","definition_or_measurement_approach":"Median time in days to achieve and maintain clinical success after last injection; timing measured per scheduled visits."}
• {"endpoint_text":"-Percentage change from baseline in contracture degree as measured by passive finger extension in 30±3 days after the last injection of V. alginolyticus collagenase into the cord in the affected primary joint as compared to matching placebo","definition_or_measurement_approach":"Percent change from baseline in contracture degree measured by passive finger extension at 30±3 days after last injection versus placebo."}
• {"endpoint_text":"-Percentage change from baseline in passive finger flexion in 30±3 days after the last injection of V. alginolyticus collagenase into the cord in the affected primary joint as compared to matching placebo","definition_or_measurement_approach":"Percent change from baseline in passive finger flexion at 30±3 days after last injection versus placebo."}
• {"endpoint_text":"-Change from baseline in the range of motion in 30±3 days after the last injection of V. alginolyticus collagenase into the cord in the affected primary joint as compared to matching placebo","definition_or_measurement_approach":"Change from baseline in range of motion at 30±3 days after last injection compared to placebo."}
• {"endpoint_text":"-Proportion of patients who achieve clinical success defined as a reduction in contracture to ≤5° in 30±3 days after each received injection of V. alginolyticus collagenase into the cord in the affected primary joint as measured by passive angle of finger extension as compared to matching placebo","definition_or_measurement_approach":"Proportion achieving ≤5° within 30±3 days after each received injection measured by passive angle of finger extension versus placebo."}
• {"endpoint_text":"-Proportion of patients who achieve a clinical improvement defined as a reduction from baseline in contracture by ≥50% in 30±3 days after each received injection of V. alginolyticus collagenase into the cord in the affected primary joint as measured by passive angle of finger extension as compared to matching placebo","definition_or_measurement_approach":"Proportion achieving ≥50% reduction from baseline within 30±3 days after each received injection measured by passive angle of finger extension versus placebo."}
• {"endpoint_text":"-Secondary endpoints in both study parts: - Blood exposure after each injection of V. alginolyticus collagenase evaluated as serum levels of V. alginolyticus collagenase at pre-dose and 10 min, 0.5, 1, and 2 h post-dose","definition_or_measurement_approach":"Serum levels measured pre-dose and at 10 min, 0.5 h, 1 h and 2 h post-dose to evaluate blood exposure."}
• {"endpoint_text":"-Immunogenicity of V. alginolyticus collagenase evaluated through assay of serum anti-drug antibodies in all subjects at pre-dose and 30±3 days post-dose","definition_or_measurement_approach":"Assay of serum anti-drug antibodies pre-dose and at 30±3 days post-dose."}
• {"endpoint_text":"-Overall safety profile of injection of V. alginolyticus collagenase or matching placebo","definition_or_measurement_approach":"Safety profile assessed through adverse events, labs, vital signs and other safety assessments per protocol."}
• {"endpoint_text":"-Follow-up endpoints: Percentage change from baseline in contracture degree as measured by passive finger extension 6 months after the last injection of V. alginolyticus collagenase into the cord in the affected primary joint as compared to matching placebo","definition_or_measurement_approach":"Percent change from baseline in contracture degree at 6 months after last injection measured by passive finger extension versus placebo."}
• {"endpoint_text":"-Proportion of patients who have an increase in joint contracture to ≥20° in the presence of a palpable cord (recurrence) as measured by passive finger extension 6 months after the last injection of V. alginolyticus collagenase into the cord in the affected primary joint as compared to matching placebo","definition_or_measurement_approach":"Proportion with recurrence (increase to ≥20° with palpable cord) measured by passive finger extension at 6 months after last injection versus placebo."}
• {"endpoint_text":"-Percentage change from baseline in passive finger flexion 6 months after the last injection of V. alginolyticus collagenase into the cord in the affected primary joint as compared to matching placebo","definition_or_measurement_approach":"Percent change from baseline in passive finger flexion at 6 months after last injection."}
• {"endpoint_text":"-Change from baseline to Month 6 in the range of motion after the last injection of V. alginolyticus collagenase into the cord in the affected primary joint as compared to matching placebo","definition_or_measurement_approach":"Change from baseline to Month 6 in range of motion after last injection compared to placebo."}
• {"endpoint_text":"-Safety profile of injection of V. alginolyticus collagenase or matching placebo after 6 months","definition_or_measurement_approach":"Safety assessments at 6 months after last injection (AEs, labs, vitals, etc.)."}
• {"endpoint_text":"-Immunogenicity of V. alginolyticus collagenase evaluated through assay of serum anti-drug antibodies in all subjects at Month 6 after the last injection","definition_or_measurement_approach":"Assay of serum anti-drug antibodies at Month 6 after last injection."}

Austria

Earliest CTIS Part Ii Submission Date

25-09-2024

Latest Decision Or Authorization Date

22-04-2026

Processing Time Days

574

Number Of Sites

2

Number Of Participants

32

Germany

Earliest CTIS Part Ii Submission Date

03-10-2024

Latest Decision Or Authorization Date

22-04-2026

Processing Time Days

566

Number Of Sites

1

Number Of Participants

11

Sweden

Earliest CTIS Part Ii Submission Date

16-09-2024

Latest Decision Or Authorization Date

22-04-2026

Processing Time Days

583

Number Of Sites

1

Number Of Participants

15

Italy

Earliest CTIS Part Ii Submission Date

06-09-2024

Latest Decision Or Authorization Date

22-04-2026

Processing Time Days

593

Number Of Sites

3

Number Of Participants

25

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.

Third parties

• {"country":"Switzerland","full_name":"Cross Research S.A.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}