Safety and Efficacy Study of Collagenase CNT201 Injection for Treatment of Dupuytren's Contracture

Phase 2RecruitingNCT07640425

CONNEXT60 enrolled

Overview

This trial is a multicenter, Phase 1/2, study to assess the safety, tolerability, efficacy, PK, and immunogenicity of CNT201 in adult participants with DC (Dupuytren's Contracture).

This is an adaptive clinical study design containing 2 steps: * Step 1 (dose escalation) is an open-label, dose escalating design where each participant will be enrolled into 1 of 4 dose levels and receive a single administration of CNT201. A Safety Review Committee (SRC) will decide on the dose escalation steps and which dose(s) will be selected to progress into Step 2 dose expansion stage. * Step 2 (dose expansion) adopts a randomized, double-blind, placebo-controlled study design. Eligible participants will be randomized to receive either CNT201 or a placebo for up to a total of 3 treatment cycles per cord at the discretion of the Investigator.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

Conditions

Dupuytren Contracture Dupuytren Disease of Finger

Interventions

[Step1] CNT201 First-doseDRUG

CNT201: recombinant collagenase • Unit Dose Strength(s)/ Dosage Level(s): First-dose

[Step1] CNT201 Low-doseDRUG

CNT201: recombinant collagenase • Unit Dose Strength(s)/ Dosage Level(s): Low-dose

[Step1] CNT201 Intermediate-doseDRUG

CNT201: recombinant collagenase • Unit Dose Strength(s)/ Dosage Level(s): Intermediate-dose

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Men and women, 18 to 75 years of age, inclusive. * Participants with a diagnosis of DC, with a fixed flexion deformity of at least 1 finger, other than the thumb, that have a contracture at least 20°, but not greater than 100°, for MP (not greater than 80° for PIP) joints, caused by a palpable cord. * Participants who have a positive Table Top Test, defined as the inability to simultaneously place the affected finger(s) and palm flat against a tabletop. * Participants who are naive to CNT201 treatment. * Participants who are judged to be in good health, based upon the results of a medical history, physical examination, and safety laboratory profile. * Participants who are willing to voluntarily sign and date the Informed Consent Form (ICF) approved by the Institutional Review Board/Independent Ethics Committee (IRB/IEC). Exclusion Criteria: * Participants previously exposed to collagenase Clostridium histolyticum for treatment of Dupuytren's disease (Xiaflex, Xiapex®). * Participants who have received other treatments for advanced Dupuytren's disease, including surgery (fasciectomy or fasciotomy), needle aponeurotomy/fasciotomy, or injection of verapamil and/or interferon on the selected primary joint within 90 days before the first dose of study treatment. * Participants with a chronic muscular, neurological, or neuromuscular disorder that affects the hands, or other medical condition which in the Investigator's opinion will make the participant unsuitable for enrollment in the study. * Participants who have a known recent history of stroke, bleeding, a disease process that affected the hands, or other medical condition (eg, testing positive for tuberculosis \[TB\] or Coronavirus disease 2019 \[COVID-19\], etc), or history of alcoholism or drug abuse, which in the Investigator's opinion, would make the participant unsuitable for enrollment in the study. * Participants who have a known allergic response to collagenase or any other excipient of CNT201 or Xiaflex. * Participants who have received a doxycycline or tetracycline derivative within 14 days before the beginning of the study (tetracycline derivatives may inhibit the collagenolytic activity of mammalian collagenase homologs). * Participants who have received an anticoagulant (except aspirin ≤150 mg/day) within 7 days before the start of the study. * Female participants who are nursing or pregnant, or plan to become pregnant during the study treatment stage of the study. * Participants who have been treated with any investigational drug within 30 days of first dose of study treatment.

Locations (1)

A R Houston Medical Pty Ltd.

Kippa-Ring, Queensland, Australia

RECRUITING

Outcomes

Primary Outcomes

[Step 1] Incidence of adverse events

Adverse events including TEAEs, SAEs, and AESIs assessed by frequency and severity, coded using MedDRA and graded per CTCAE v5.0. All adverse event types will be aggregated and reported as overall incidence of adverse events.

Time frame: Day 1 through Day 57

[Step 1] Change from baseline in systolic and diastolic blood pressure

Systolic and diastolic blood pressure will be measured in mmHg, and the change from baseline will be evaluated at each scheduled visit.

Time frame: Screening, Day 1 (pre-dose and post-dose up to 6 hours), Day 2, 3, 8, 15, 29, and Day 57

[Step 1] Change from baseline in pulse rate

Pulse rate will be measured in beats per minute (bpm), and the change from baseline will be assessed at each scheduled visit.

Time frame: Screening, Day 1 (pre-dose and post-dose up to 6 hours), Day 2, 3, 8, 15, 29, and Day 57

[Step 1] Change from baseline in respiratory rate

Respiratory rate will be measured in breaths per minute, and the change from baseline will be evaluated at each scheduled visit.

Time frame: Screening, Day 1 (pre-dose and post-dose up to 6 hours), Day 2, 3, 8, 15, 29, and Day 57

[Step 1] Change from baseline in body temperature

Body temperature will be measured in degrees Celsius (°C), and the change from baseline will be evaluated at each scheduled visit.

Time frame: Screening, Day 1 (pre-dose and post-dose up to 6 hours), Day 2, 3, 8, 15, 29, and Day 57

[Step 1] Change from baseline in 12-lead ECG parameters

Electrocardiogram (ECG) parameters including heart rate, PR interval, QRS duration, QT interval, and corrected QT interval using Fridericia's formula (QTcF) will be assessed using automated 12-lead ECG recordings.

Central Contacts

Suntae Kim

CONTACT

+82-10-5682-2489 suntae.kim@connext.co.kr

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

CNT201: recombinant collagenase • Unit Dose Strength(s)/ Dosage Level(s): High-dose

[Step2] CNT201DRUG

eligible participants will be randomized to 1 of 2 or more treatment arms, depending on the number of CNT201 doses selected for administration in Step 2

[Step2] PlaceboDRUG

• Saline

Time frame: Screening and Day 1 (1 hour post-dose)

[Step 1] Number of Participants with Clinically Significant Changes in Clinical Laboratory Test Results

Clinical laboratory assessments include hematology, clinical chemistry, coagulation, and urinalysis parameters. The number of participants with clinically significant changes from baseline will be summarized.

Time frame: Screening and Day 57

[Step 1] Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

Complete physical examinations were performed at scheduled visits. Clinically significant abnormalities, including injection site reactions, were recorded and summarized as the number of participants with abnormalities.

Time frame: Screening, Day 1 (pre-dose), Day29, and Day 57

[Step 1] Proportion of participants achieving reduction in contracture to within 0-5° of normal extension

Finger joint contracture (MP and PIP joints) measured by goniometry.

Time frame: Within 29 days of study treatment injection

[Step 2] Incidence of TEAEs, SAEs, and AESIs by severity

Frequency and severity of adverse events coded using MedDRA and graded per CTCAE v5.0.

Time frame: Screening through Month 12

[Step 2] Change from baseline in systolic and diastolic blood pressure

Systolic and diastolic blood pressure will be measured in mmHg, and the change from baseline will be evaluated at each scheduled visit.

Time frame: Screening, Day 1 of each injection cycle (pre-dose and post-dose up to 48 hours), Day 3, 8, 29 of each cycle, and Month 12 (each cycle is 28 days)

[Step 2] Change from baseline in pulse rate

Pulse rate will be measured in beats per minute (bpm), and the change from baseline will be assessed at each scheduled visit.

Time frame: Screening, Day 1 of each injection cycle (pre-dose and post-dose up to 48 hours), Day 3, 8, 29 of each cycle, and Month 12 (each cycle is 28 days)

[Step 2] ] Change from baseline in respiratory rate

Respiratory rate will be measured in breaths per minute, and the change from baseline will be evaluated at each scheduled visit.

Time frame: Screening, Day 1 of each injection cycle (pre-dose and post-dose up to 48 hours), Day 3, 8, 29 of each cycle, and Month 12 (each cycle is 28 days)

[Step 2] Change from baseline in body temperature

Body temperature will be measured in degrees Celsius (°C), and the change from baseline will be evaluated at each scheduled visit.

Time frame: Screening, Day 1 of each injection cycle (pre-dose and post-dose up to 48 hours), Day 3, 8, 29 of each cycle, and Month 12 (each cycle is 28 days)

[Step 2] Change from Baseline in Electrocardiogram Parameters

Time frame: Screening and Day 1 (1 hour post-dose) of each cycle (each cycle is 28 days)

[Step 2] Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

Time frame: Screening, Day 1 of each injection cycle (pre-dose), Day 29 of each cycle and Month 12 (each cycle is 28 days)

[Step 2] Number of Participants with Clinically Significant Changes in Clinical Laboratory Test Results

Time frame: Screening through Week 52

[Step 2] Proportion of participants achieving reduction in contracture to within 0-5° of normal extension within 29 days after the first injection

Finger joint contracture (MP and PIP joints) measured by goniometry.

Time frame: Within 29 days after first injection

Secondary Outcomes

[Step 1] Proportion of participants achieving clinical improvement (≥50% reduction in contracture from Day 1)

Assessed by finger goniometry at each scheduled visit.

Time frame: Screening, Day 1 (pre-dose and 6 hours post-dose), Day 3, 8, 15, 29, and Day 57

[Step 1] Mean percent change in degree of contracture

Assessed by finger goniometry (MP and PIP joints).

Time frame: Screening, Day 1 (pre-dose and 6 hours post-dose), Day 3, 8, 15, 29, and Day 57

[Step 1] Time to clinical success (contracture ≤5°)

Defined as the first study day on which treated joint contracture is ≤5°.

Time frame: Screening, Day 1 (pre-dose and 6 hours post-dose), Day 3, 8, 15, 29, and Day 57

[Step 1] Change in range of motion (full extension, full flexion, and total arc)

Assessed by finger goniometry (MP and PIP joints).

Time frame: Screening, Day 1 (pre-dose and 6 hours post-dose), Day 3, 8, 15, 29, and Day 57

[Step 1] Participant Global Assessment of Treatment Satisfaction Score

Treatment satisfaction will be assessed by the investigator using a study-specific 5-point Likert scale (1 = Very satisfied, 2 = Satisfied, 3 = Neither satisfied nor dissatisfied, 4 = Dissatisfied, 5 = Very dissatisfied). Lower scores indicate greater satisfaction.

Time frame: Screening, Day 29, and Day 57

[Step 1] Physician Global Assessment of Disease Severity Score

Disease/contracture severity will be assessed by the investigator using a study-specific 4-point scale (1 = Normal, 2 = Mild, 3 = Moderate, 4 = Severe). Higher scores indicate greater severity.

Time frame: Screening, Day 29, and Day 57

[Step 1] Physician Global Assessment of Treatment Satisfaction Score

Time frame: Screening, Day 29, and Day 57

[Step 1] Peak plasma concentration (Cmax) of CNXT1 and CNXT2