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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:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| [Step1] CNT201 First-dose | Experimental |
| |
| [Step1] CNT201 Low-dose | Experimental |
| |
| [Step1] CNT201 Intermediate-dose | Experimental |
| |
| [Step1] CNT201 High-dose | Experimental |
| |
| [Step2] CNT201 | Experimental |
| |
| [Step2] Placebo | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| [Step1] CNT201 First-dose | Drug | CNT201: recombinant collagenase • Unit Dose Strength(s)/ Dosage Level(s): First-dose |
|
| 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. |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Suntae Kim | Contact | +82-10-5682-2489 | suntae.kim@connext.co.kr |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| A R Houston Medical Pty Ltd. | Recruiting | Kippa-Ring | Queensland | 4021 | Australia |
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This is an adaptive clinical study design containing 2 steps:
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| [Step1] CNT201 Low-dose | Drug | CNT201: recombinant collagenase • Unit Dose Strength(s)/ Dosage Level(s): Low-dose |
|
| [Step1] CNT201 Intermediate-dose | Drug | CNT201: recombinant collagenase • Unit Dose Strength(s)/ Dosage Level(s): Intermediate-dose |
|
| [Step1] CNT201 High-dose | Drug | CNT201: recombinant collagenase • Unit Dose Strength(s)/ Dosage Level(s): High-dose |
|
| [Step2] CNT201 | Drug | 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] Placebo | Drug | • Saline |
|
| 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 |
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) |
| ID | Term |
|---|---|
| D004387 | Dupuytren Contracture |
| ID | Term |
|---|---|
| D005350 | Fibroma |
| D018218 | Neoplasms, Fibrous Tissue |
| D009372 | Neoplasms, Connective Tissue |
| D018204 | Neoplasms, Connective and Soft Tissue |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D003286 | Contracture |
| D009135 | Muscular Diseases |
| D009140 | Musculoskeletal Diseases |
| D003240 | Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
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