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

Официальное название

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

Обзор

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).

Подробное описание

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.

Вмешательства

• Препарат [Step1] CNT201 First-dose
  CNT201: recombinant collagenase • Unit Dose Strength(s)/ Dosage Level(s): First-dose
• Препарат [Step1] CNT201 Low-dose
  CNT201: recombinant collagenase • Unit Dose Strength(s)/ Dosage Level(s): Low-dose
• Препарат [Step1] CNT201 Intermediate-dose
  CNT201: recombinant collagenase • Unit Dose Strength(s)/ Dosage Level(s): Intermediate-dose
• Препарат [Step1] CNT201 High-dose
  CNT201: recombinant collagenase • Unit Dose Strength(s)/ Dosage Level(s): High-dose
• Препарат [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
• Препарат [Step2] Placebo
  • Saline

Первичные конечные точки

• [Step 1] Incidence of adverse events [Срок оценки: Day 1 through Day 57]
• [Step 1] Change from baseline in systolic and diastolic blood pressure [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: Screening and Day 1 (1 hour post-dose)]
• [Step 1] Number of Participants with Clinically Significant Changes in Clinical Laboratory Test Results [Срок оценки: Screening and Day 57]
• [Step 1] Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [Срок оценки: 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 [Срок оценки: Within 29 days of study treatment injection]
• [Step 2] Incidence of TEAEs, SAEs, and AESIs by severity [Срок оценки: Screening through Month 12]

Вторичные конечные точки (12)

• [Step 1] Proportion of participants achieving clinical improvement (≥50% reduction in contracture from Day 1) [Срок оценки: 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 [Срок оценки: 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°) [Срок оценки: 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) [Срок оценки: 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 [Срок оценки: Screening, Day 29, and Day 57]
• [Step 1] Physician Global Assessment of Disease Severity Score [Срок оценки: Screening, Day 29, and Day 57]
• [Step 1] Physician Global Assessment of Treatment Satisfaction Score [Срок оценки: Screening, Day 29, and Day 57]
• [Step 1] Peak plasma concentration (Cmax) of CNXT1 and CNXT2 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: Day 1 (pre-dose through 48 hours post-dose), Day 3, 4, 5, 6, 7]
• [Step 1] Half-life (t½) of CNXT1 and CNXT2 [Срок оценки: Day 1 (pre-dose through 48 hours post-dose), Day 3, 4, 5, 6, 7]
• [Step 1] Clearance (CL) of CNXT1 and CNXT2 [Срок оценки: Day 1 (pre-dose through 48 hours post-dose), Day 3, 4, 5, 6, 7]

Критерии участия

Критерии включения

• 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).

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

Австралия · 1 центр

• A R Houston Medical Pty Ltd. — Kippa-Ring

Идентификаторы

NCT: NCT07640425 · DC2201

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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