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

A Phase 1/2, Multicenter, Dose Escalating, Dose Expanding, Adaptive Study to Assess Safety, Tolerability, Efficacy and Pharmacokinetics of Collagenase CNT201 in Adult Participants With Dupuytren's Contracture

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).

Study Overview

• Status: Recruiting
• Conditions: Dupuytren Contracture; Dupuytren Disease of Finger
• Intervention / Treatment: Drug: [Step1] CNT201 First-dose; Drug: [Step1] CNT201 Low-dose; Drug: [Step1] CNT201 Intermediate-dose; Drug: [Step1] CNT201 High-dose; Drug: [Step2] CNT201; Drug: [Step2] Placebo

Detailed Description

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
• Enrollment (Estimated): 60
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Suntae Kim; Phone Number: +82-10-5682-2489; Email: suntae.kim@connext.co.kr

Study Locations

• Australia
  • Queensland
    • Kippa-Ring, Queensland, Australia, 4021
      • Recruiting
      • A R Houston Medical Pty Ltd.
      • Contact: Anthony R Houston, MD
      • Principal Investigator: Anthony R Houston, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: [Step1] CNT201 First-dose	Drug: [Step1] CNT201 First-dose; CNT201: recombinant collagenase • Unit Dose Strength(s)/ Dosage Level(s): 0.1 mg/cord
Experimental: [Step1] CNT201 Low-dose	Drug: [Step1] CNT201 Low-dose; CNT201: recombinant collagenase • Unit Dose Strength(s)/ Dosage Level(s): 0.3 mg/cord
Experimental: [Step1] CNT201 Intermediate-dose	Drug: [Step1] CNT201 Intermediate-dose; CNT201: recombinant collagenase • Unit Dose Strength(s)/ Dosage Level(s): 0.6 mg/cord
Experimental: [Step1] CNT201 High-dose	Drug: [Step1] CNT201 High-dose; CNT201: recombinant collagenase • Unit Dose Strength(s)/ Dosage Level(s): 0.8 mg/cord
Experimental: [Step2] CNT201	Drug: [Step2] CNT201; 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
Placebo Comparator: [Step2] Placebo	Drug: [Step2] Placebo; • Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
[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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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	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.	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	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.	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	Clinical laboratory assessments include hematology, clinical chemistry, coagulation, and urinalysis parameters. The number of participants with clinically significant changes from baseline will be summarized.	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.	Within 29 days after first injection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
[Step 1] Proportion of participants achieving clinical improvement (≥50% reduction in contracture from Day 1)	Assessed by finger goniometry at each scheduled visit.	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).	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°.	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).	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.	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.	Screening, Day 29, and Day 57
[Step 1] Physician 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.	Screening, Day 29, and Day 57
[Step 1] Peak plasma concentration (Cmax) of CNXT1 and CNXT2	Assessed from plasma concentrations of CNXT1 and CNXT2 collected at scheduled timepoints.	Day 1 (pre-dose through 48 hours post-dose), Day 3, 4, 5, 6, 7
[Step 1] Time to peak plasma concentration (tmax) of CNXT1 and CNXT2	Assessed from plasma concentrations of CNXT1 and CNXT2 collected at scheduled timepoints.	Day 1 (pre-dose through 48 hours post-dose), Day 3, 4, 5, 6, 7
[Step 1] Area under the plasma concentration-time curve (AUC) of CNXT1 and CNXT2	Assessed from plasma concentrations of CNXT1 and CNXT2 collected at scheduled timepoints.	Day 1 (pre-dose through 48 hours post-dose), Day 3, 4, 5, 6, 7
[Step 1] Half-life (t½) of CNXT1 and CNXT2	Assessed from plasma concentrations of CNXT1 and CNXT2 collected at scheduled timepoints.	Day 1 (pre-dose through 48 hours post-dose), Day 3, 4, 5, 6, 7
[Step 1] Clearance (CL) of CNXT1 and CNXT2	Assessed from plasma concentrations of CNXT1 and CNXT2 collected at scheduled timepoints.	Day 1 (pre-dose through 48 hours post-dose), Day 3, 4, 5, 6, 7
[Step 1] Volume of distribution (Vd/F) of CNXT1 and CNXT2	Assessed from plasma concentrations of CNXT1 and CNXT2 collected at scheduled timepoints.	Day 1 (pre-dose through 48 hours post-dose), Day 3, 4, 5, 6, 7
[Step 1] Incidence of anti-drug antibodies against CNXT1 and CNXT2	Antibody incidence, titers, and neutralizing antibodies assessed from blood samples.	Day 1 (pre-dose), Day 15, 29, and Day 57
[Step 2] Proportion of participants achieving contracture ≤5° of normal extension at Day 85 after first injection	Assessed by finger goniometry.	Day 85 after first injection
[Step 2] Proportion of participants achieving contracture ≤5° of normal extension within 29 days after the last injection	Assessed by finger goniometry.	Within 29 days after last injection
[Step 2] Proportion of participants achieving clinical improvement (≥50% reduction in contracture from Day 1)	Assessed by finger goniometry at each scheduled visit.	Screening, Day 1 of each injection cycle (pre-dose), Day 3, 8, 29 of each cycle, Month 2, 3, 4, 6, 9, and Month 12 (each cycle is 28 days)
[Step 2] Mean percent change in degree of contracture	Assessed by finger goniometry (MP and PIP joints).	Screening, Day 1 of each injection cycle (pre-dose), Day 3, 8, 29 of each cycle, Month 2, 3, 4, 6, 9, and Month 12 (each cycle is 28 days)
[Step 2] Time to clinical success (contracture ≤5°)	Defined as the first study day on which treated joint contracture is ≤5°.	Screening, Day 1 of each injection cycle (pre-dose), Day 3, 8, 29 of each cycle, Month 2, 3, 4, 6, 9, and Month 12 (each cycle is 28 days)
[Step 2] Change in range of motion (full extension, full flexion, and total arc)	Assessed by finger goniometry (MP and PIP joints).	Screening, Day 1 of each injection cycle (pre-dose), Day 3, 8, 29 of each cycle, Month 2, 3, 4, 6, 9, and Month 12 (each cycle is 28 days)
[Step 2] 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.	Screening, Day 29 of each injection cycle, and Month 12 (each cycle is 28 days)
[Step 2] 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.	Screening, Day 29 of each injection cycle, and Month 12 (each cycle is 28 days)
[Step 2] Physician 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.	Screening, Day 29 of each injection cycle, and Month 12 (each cycle is 28 days)
[Step 2] Time to recurrence	Defined as an increase in joint contracture to ≥20° in the presence of a palpable cord.	Month 2, 3, 4, 6, 9, and Month 12
[Step 2] Proportion of participants with contracture recurrence at Month 12	Recurrence defined as joint contracture ≥20° in the presence of a palpable cord.	Month 12
[Step 2] Incidence of anti-drug antibodies against CNXT1 and CNXT2	Antibody incidence, titers, and neutralizing antibodies assessed from blood samples.	Screening, Day 1 of Cycle 1, Month 2, 3, 4, 6, 9, and Month 12 (each cycle is 28 days)

Collaborators and Investigators

• Sponsor: CONNEXT

Study record dates

Study Major Dates

• Study Start (Actual): July 23, 2024
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 25, 2027

Study Registration Dates

• First Submitted: August 23, 2024
• First Submitted That Met QC Criteria: June 5, 2026
• First Posted (Actual): June 10, 2026

Study Record Updates

• Last Update Posted (Actual): June 10, 2026
• Last Update Submitted That Met QC Criteria: June 5, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: collagenase injection; CCH; CNT201
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Muscular Diseases; Neoplasms; Connective Tissue Diseases; Neoplasms by Histologic Type; Neoplasms, Connective and Soft Tissue; Neoplasms, Connective Tissue; Neoplasms, Fibrous Tissue; Fibroma; Contracture; Skin and Connective Tissue Diseases; Dupuytren Contracture
• Other Study ID Numbers: DC2201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No