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Trial registered on ANZCTR


Registration number
ACTRN12624000664549
Ethics application status
Approved
Date submitted
5/04/2024
Date registered
24/05/2024
Date last updated
16/06/2024
Date data sharing statement initially provided
24/05/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
CNT201 Phase 1/2 study in Adults with Dupuytren’s Contracture
Scientific title
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
Secondary ID [1] 311862 0
DC2201
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Dupuytren’s Contracture 333410 0
Condition category
Condition code
Human Genetics and Inherited Disorders 330090 330090 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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.
Intervention code [1] 328324 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 337848 0
Step 1 (Dose escalation) Safety and tolerability of CNT201
Timepoint [1] 337848 0
Step 1 (Dose escalation) Assessments will be conducted on Screening, Day 1 (before injection, baseline, 15 min, 30 min, 45 min, 1 hr, 2 hr, 4 hr and 6 hrs), Day 2, Day 3, Day 8, Day 15, Day 29 and Day 57 post dose
Primary outcome [2] 337849 0
Step 1 (Dose escalation) Safety and tolerability of CNT201
Timepoint [2] 337849 0
Step 1 (Dose escalation) At screening, predose on Day 1, post dose on Day 1, Day 2, Day 3, Day 8, Day 15, Day 29, Day 57 (end of study)
Primary outcome [3] 337850 0
Step 1 (Dose escalation) Safety and tolerability of CNT201
Timepoint [3] 337850 0
Step 1 (Dose escalation) At screening and on Day 1 post dose
Secondary outcome [1] 433463 0
Step 1 (Dose escalation) - Primary Outcome 4- Safety and tolerability of CNT201
Timepoint [1] 433463 0
Step 1 (Dose escalation)- Primary Outcome 4 - At screening, Predose on Day 1 and Day 29 post dose
Secondary outcome [2] 433464 0
Step 1 (Dose escalation) -Primary Outcome 5- Safety and tolerability of CNT201
Timepoint [2] 433464 0
Step 1 (Dose escalation)- Primary Outcome 5- At screening, Predose on Day 1, Post dose on Day 29, Day 57 (EOS)
Secondary outcome [3] 433465 0
Step 1 (Dose escalation)- Primary outcome 6- Assess the efficacy of CNT201 in reducing the degree of contracture after injection.
Timepoint [3] 433465 0
Step 1 (Dose escalation) - Primary Outcome 6 -At screening, pre dose on Day 1, Post dose on Day 1, Day 6, Day 2, Day 3, Day 8, Day 15, Day 29 and Day 57 (EoS)
Secondary outcome [4] 433466 0
Step 1 (Dose escalation) : Assess the change in the primary joint after the study treatment injection
Timepoint [4] 433466 0
Step 1 (Dose escalation): At Screening, Predose , Post dose on Day 1 (1 hour, 6 hours), Day 2, Day 3, Day 8, Day 15, Day 29, and Day 57 (EoS)
Secondary outcome [5] 434094 0
Step 1 (Dose escalation) : Assess the change in the primary joint after the study treatment injection
Timepoint [5] 434094 0
Step 1 (Dose escalation): At Screening, Predose , Post dose on Day 1 (1 hour, 6 hours), Day 2, Day 3, Day 8, Day 15, Day 29, and Day 57 (EoS)
Secondary outcome [6] 434096 0
Step 1 (Dose escalation) : Clinical Evaluation in the primary joint after study treatment injection
Timepoint [6] 434096 0
Step 1 (Dose escalation): At Screening, Predose , Post dose on Day 1 (1 hour, 6 hours), Day 2, Day 3, Day 8, Day 15, Day 29, and Day 57 (EoS)
Secondary outcome [7] 434097 0
Step 1 (Dose escalation) : Assess the change in the primary joint after the study treatment injection
Timepoint [7] 434097 0
Step 1 (Dose escalation): At Screening, Predose , Post dose on Day 1 (1 hour, 6 hours), Day 2, Day 3, Day 8, Day 15, Day 29, and Day 57 (EoS)
Secondary outcome [8] 434312 0
Step 1 (Dose escalation) : Assess the change in the primary joint after the study treatment injection
Timepoint [8] 434312 0
On Day 1 (Pre-dose), Day 29 and Day 57 (EoS)
Secondary outcome [9] 435022 0
Step 1 (Dose escalation) : Assess the change in the primary joint after the study treatment injection

Finger goniometry will be used to measure range of motion to determine the degree of finger extension and evaluate the proportion of participants with clinical improvement, change in degree of contracture, change in range of motion, and time to clinical success.
Timepoint [9] 435022 0
Step 1 (Dose escalation): At Screening, Predose , Post dose on Day 1 (1 hour, 6 hours), Day 2, Day 3, Day 8, Day 15, Day 29, and Day 57 (EoS)
Secondary outcome [10] 435023 0
Step 1 (Dose escalation) : Assess the change in the primary joint after the study treatment injection
Timepoint [10] 435023 0
Step 1 (Dose escalation): At Screening, Predose , Post dose on Day 1 (1 hour, 6 hours), Day 2, Day 3, Day 8, Day 15, Day 29, and Day 57 (EoS)
Secondary outcome [11] 435026 0
Step 1 (Dose escalation) : Assess the change in the primary joint after the study treatment injection
Timepoint [11] 435026 0
On Day 1 (Pre-dose), Day 29 and Day 57 (EoS)
Secondary outcome [12] 435027 0
Step 1 (Dose escalation) : Assess the change in the primary joint after the study treatment injection
Timepoint [12] 435027 0
On Day 1 (Pre-dose), Day 29 and Day 57 (EoS)
Secondary outcome [13] 435028 0
Step 1 (Dose escalation) : Assess the change in the primary joint after the study treatment injection
Timepoint [13] 435028 0
On Day 1 (Pre-dose), Day 29 and Day 57 (EoS)

Eligibility
Key inclusion criteria
1. Men and women, 18 to 75 years of age, inclusive.
2. 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.
3. 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.
4. 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.
5. Participants who are naive to CNT201 treatment.
6. Participants who are judged to be in good health, based upon the results of a medical history, physical examination, and safety laboratory profile.
7. 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).
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Participants previously exposed to collagenase Clostridium histolyticum for treatment of Dupuytren’s disease (Xiaflex, Xiapex®).
2. 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.
3. 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.
4. 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.
5. 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.
6. 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).
7. Participants with secondary DC due to diabetes or liver disease.
8. Participants with osteoarthritis or rheumatoid arthritis in the hands, determined by the Investigator based on their review, clinical examination, or X-ray assessment.
9. Participants who are human immunodeficiency virus (HIV) positive.
10. Participants who have an active infection of tuberculosis (TB).
11. Participants who have a known allergic response to collagenase or any other excipient of CNT201.
12. 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).
13. 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.
14. Female participants who are nursing or pregnant, or plan to become pregnant during the study treatment stage of the study.
15. Participants who have been treated with any investigational drug within 30 days of first dose of study treatment

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 1 / Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
20/06/2024
Actual
Date of last participant enrolment
Anticipated
17/05/2025
Actual
Date of last data collection
Anticipated
18/07/2025
Actual
Sample size
Target
36
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD

Funding & Sponsors
Funding source category [1] 316205 0
Commercial sector/Industry
Name [1] 316205 0
Connext Co., Ltd
Country [1] 316205 0
Korea, Republic Of
Primary sponsor type
Commercial sector/Industry
Name
Connext Co., Ltd
Address
Country
Korea, Republic Of
Secondary sponsor category [1] 318389 0
Commercial sector/Industry
Name [1] 318389 0
Novotech (Australia) Pty Ltd.
Address [1] 318389 0
Country [1] 318389 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 315022 0
Bellberry Human Research Ethics Committee A
Ethics committee address [1] 315022 0
https://bellberry.com.au/
Ethics committee country [1] 315022 0
Australia
Date submitted for ethics approval [1] 315022 0
12/04/2024
Approval date [1] 315022 0
21/05/2024
Ethics approval number [1] 315022 0
2024-04-447
Ethics committee name [2] 315023 0
Gold Coast Hospital and Health Service Human Research Ethics Committee
Ethics committee address [2] 315023 0
https://www.goldcoast.health.qld.gov.au/research/researchers/ethics/human-research-ethics-committee
Ethics committee country [2] 315023 0
Australia
Date submitted for ethics approval [2] 315023 0
15/06/2024
Approval date [2] 315023 0
Ethics approval number [2] 315023 0

Summary
Brief 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 (Connext Co., Ltd.), 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.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 133454 0
Dr Randipsingh Bindra
Address 133454 0
Gold Coast University Hospital, 1 Hospital Boulevard, Southport, Queensland Australia 4215
Country 133454 0
Australia
Phone 133454 0
+617 56874860
Fax 133454 0
Email 133454 0
r.bindra@griffith.edu.au
Contact person for public queries
Name 133455 0
Suntae Kim
Address 133455 0
Connext Co., Ltd., Suite 505, 76 Dongnae-ro, Dong-gu Daegu, Republic of Korea 41061
Country 133455 0
Korea, Republic Of
Phone 133455 0
+821056822489
Fax 133455 0
Email 133455 0
suntae.kim@connext.co.kr
Contact person for scientific queries
Name 133456 0
Suntae Kim
Address 133456 0
Connext Co., Ltd., Suite 505, 76 Dongnae-ro, Dong-gu Daegu, Republic of Korea 41061
Country 133456 0
Korea, Republic Of
Phone 133456 0
+821056822489
Fax 133456 0
Email 133456 0
suntae.kim@connext.co.kr

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.