CNT201 Phase 1/2 study in Adults with 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
Connext Co., Ltd
36 participants
Jul 23, 2024
Interventional
Conditions
Summary
Study details This registration is for Step 1 of a 2 step study investigating CNT201. CNT201 is a recombinant collagenase product being developed by the Sponsor, which is being studied for the treatment of Dupuytren’s Contracture (DC) This is an adaptive clinical study design containing 2 steps (Dose escalation and Dose expansion). Step 1 (dose escalation) uses an open-label design. Participants will be enrolled to a dose cohort with the CNT201 dose to be administered determined by the cohort to which the participant is enrolled; Afte a screening period of upto 30 days, eligible participants will be enrolled into 1 of 4 cohorts (provisional 5th cohort) and will be administered a single dose of CNT201 at 1 of 4 CNT201 dose levels: First-, low-, intermediate-, or high-dose (Cohort 1 to Cohort 4, respectively) within a treatment cycle. The treatment period will consist of an intralesional injection of CNT201 (Day 1), followed by a series of safety, efficacy, PK, and immunogenicity evaluations for 28 days (until Day 29) with primary efficacy assessed on Day 29 with an additional 28 days of safety follow-up thereafter (until Day 57). If there are no safety concerns on Day 57 as assessed by the investigator, Day 57 will serve as the End-of-Study (EOS) visit for Step 1. Cohort 1 will enroll 4 participants; all other cohorts will enroll 8 participants.
Eligibility
Inclusion Criteria7
- Men and women, 18 to 75 years of age, inclusive.
- Women to be included in the study are postmenopausal or agree to use contraception throughout the course of the study. Men should also agree to use a contraceptive method throughout the course of the study.
- Participants with a diagnosis of primary DC, with a fixed flexion deformity of at least 1 finger, other than the thumb, that has a contracture at least 20°, but not greater than 100°, for metacarpophalangeal (MP) not greater than 80° for Proximal interphalangeal (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 table top.
- 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 Criteria16
- Participants previously exposed to collagenase Clostridium histolyticum for treatment of Dupuytren’s disease (Xiaflex, Xiapex®).
- Participants who exhibit a recurrent DC affecting the selected primary joint, along with a history of other treatments for advanced Dupuytren’s disease, including surgery (fasciectomy or fasciotomy), needle aponeurotomy/fasciotomy.
- Participants who have received injection of verapamil, steroids 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 (e.g., breast cancer patients with enlarged lymph nodes 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 with active cardiovascular disease including clinically significant arrhythmias or prolonged QT interval (QTc greater than 450 msec for males and greater than 470 msec for females).
- Participants with secondary DC due to diabetes or liver disease.
- Participants with osteoarthritis or rheumatoid arthritis in the hands, determined by the Investigator based on their review, clinical examination, or X-ray assessment.
- Participants who are human immunodeficiency virus (HIV) positive.
- Participants who have an active infection of tuberculosis (TB).
- Participants who have a known allergic response to collagenase or any other excipient of CNT201.
- 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 less than or equal to 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
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Interventions
Interventional Product (IP): CNT201 recombinant collagenase Dosage form: Injectable Solution Mode of administration: Intralesional injection by a syringe to a single cord In Step 1 (Dose escalation), eligible participants will receive single injection of the designated CNT201 of 1 of 4 dose levels (with a provisional 5th dose level) on Day 1 of a 28 day treatment cycle with additional follow up until Day 57. A range of doses starting at 0.1 mg/kg up to 0.8 mg/kg or lower, as determined by the safety results, will be studied across up to 5 participant cohorts. Dose escalation to next higher dose cohort will be made by the safety review committee. 4 participants will be enrolled in Cohort 1 and 8 participants in all other cohorts. The SRC might recommend an additional optional fifth cohort that is a de-escalating dose lower than Cohort 1 or any dose between Cohort 1 and Cohort 4 in Step 1 (dose escalation). This optional fifth dose would be lower than the last completed highest dose level if emerging data suggests that exploring an intermediate dose before proceeding to Step 2 is warranted. However, it should not exceed the last completed highest dose level (i.e. optional fifth cohort will be 0.5mg/cord, if Cohort 3 (0.6mg/cord) was completed. And optional fifth cohort will be 0.7mg/cord, if Cohort 4 (0.8mg/cord) was completed). We will not escalate higher than high dose (0.8mg/cord).. Only authorized study center staff will supply and administer the study treatment.
Locations(1)
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ACTRN12624000664549