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).

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.

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.