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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06263270




Registration number
NCT06263270
Ethics application status
Date submitted
10/01/2024
Date registered
16/02/2024
Date last updated
16/04/2024

Titles & IDs
Public title
Evaluation of CYT-108, a Recombinant Protease Inhibitor, for Treatment of Mild to Moderate Primary Osteoarthritis of the Knee
Scientific title
A Phase Ia, Multicenter, Double-Blind, Placebo-controlled Study to Evaluate the Safety of CYT-108 for the Therapy of Mild to Moderate Primary Osteoarthritis of the Knee
Secondary ID [1] 0 0
12-2023-01
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Osteoarthritis, Knee 0 0
Osteoarthritis 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Osteoarthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - CYT-108, a recombinant protease inhibitor
Other interventions - Phosphate Buffered Saline (PBS)

Active comparator: Active Treatment Arm (CYT-108) - One intra articular (IA) injection of 5mL at 5mg/mL into one target knee with mild to moderate OA for total of 25mg CYT-108 on Days 1 and 85 (2 injections \[50 mg\] in total).

Placebo comparator: Placebo Control Arm (Phosphate Buffered Saline) - Equivalent volume 5mL of phosphate buffer saline, PBS (equal volume to the active treatment arm injection) at the same time intervals as the treatment arm.


Treatment: Other: CYT-108, a recombinant protease inhibitor
CYT-108 is a recombinant alpha-2-macroglobulin (A2M) variant engineered with increased potency against A Disintegrin and Metalloproteinase with Thrombospondin motifs (ADAMTS) substrates while possessing strong activity against Matrix Metalloproteinases (MMPs) and serine proteases. This A2M variant was engineered with amino acid modifications to the "bait" region (i.e., protease-binding region) of the A2M protein to make the variant at least two fold more effective in inhibiting ADAMTSs compared to wt-A2M without affecting its inhibitory activity toward other proteases (see Investigator Brochure). CYT-108 is not expected to cure osteoarthritis (OA), but it is expected to be the first treatment to slow disease progression by inhibiting cartilage breakdown, resulting in clinically significant outcomes such as pain reduction and improvement in mobility. This hypothesis is supported by our preliminary findings in multiple safety and efficacy studies conducted in rat and canine models of OA.

Other interventions: Phosphate Buffered Saline (PBS)
Phosphate Buffered Saline (PBS)
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Adverse Events
Timepoint [1] 0 0
Day 0; Weeks 1, 4, 8, 12, 16, 26
Primary outcome [2] 0 0
Blood Pressure
Timepoint [2] 0 0
Day 0; Weeks 1, 4, 8, 12, 16, 26
Primary outcome [3] 0 0
Heart Rate
Timepoint [3] 0 0
Day 0; Weeks 1, 4, 8, 12, 16, 26
Primary outcome [4] 0 0
Respiratory Rate
Timepoint [4] 0 0
Day 0; Weeks 1, 4, 8, 12, 16, 26
Primary outcome [5] 0 0
Body Temperature
Timepoint [5] 0 0
Day 0; Weeks 1, 4, 8, 12, 16, 26
Primary outcome [6] 0 0
Titer of Human Anti-Drug Antibody
Timepoint [6] 0 0
Day 0; Weeks 1, 4, 8, 12, 16, 26
Secondary outcome [1] 0 0
Change in WOMAC Scores (Pain, Stiffness, and Difficulty Performing Daily Activities)
Timepoint [1] 0 0
Day 0; Weeks 1, 4, 8, 12, 16, 26
Secondary outcome [2] 0 0
Time of Onset
Timepoint [2] 0 0
Day 0; Weeks 1, 4, 8, 12, 16, 26

Eligibility
Key inclusion criteria
1. Participant with mild to moderate primary knee OA.
2. Provides signed written informed consent before any study procedure is performed.
3. Is willing and able to complete effectiveness and safety questionnaires and can read and understand study instructions.
4. Adult aged 18 years or older at the time of informed consent.
5. Participants of childbearing potential must have a negative serum pregnancy test at screening and negative urine pregnancy test pre-dose on Day 1, and must agree to remain sexually abstinent, or use medically effective contraception (refer to Appendix 14.2) or have a partner who is sterile or same sex, from Screening until at least 3 months after the last treatment. Participants must not be planning to father children or donate sperm from Screening until at least 3 months after the last treatment.
6. Male participants must agree to use a double method of contraception to prevent partner's pregnancy during and 3 months after the last treatment. Male participant should not donate sperm during the same period (for more detail see appendix 14.2).
7. Is ambulatory (assistive devices or knee braces are allowed if used during the study).
8. Has symptomatic OA in the target knee (one knee) either medial or lateral.

* X-ray confirmation of OA at the target knee prior to screening with a grade 2 or 3 score on the K-L grading scale (Kellgren, 1957) using X-ray performed within 6 months of Screening.
* Knee pain as demonstrated by an average WOMAC pain scale score of 1.5 - 3 at Screening and pre-dose Day 1.
9. Remains symptomatic despite having received standard of- care therapy, such as daily doses of NSAID or any pain medication leading to the study screening.
10. Has not received corticosteroid injection within 6 weeks prior to screening.
11. Has not received hyaluronic acid treatment, Platelet rich plasma (PRP) or any other protein based or stem cells treatment, or any investigational drug within 12 weeks prior to screening.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Any of the following:

1. Grade 4 score on the K-L grading scale for the target knee
2. Grade 3 score on the K-L grading scale and exhibits at least one Grade 4 characteristic (large osteophytes, marked narrowing of joint space, severe sclerosis, or definite deformity of bone contour)
3. Acute fracture of the lower limb
4. Participant with OA in both knees.
2. Medical history of severe bone disease (e.g., osteoporosis, osteonecrosis, joint deformity, instability, or septic arthritis).
3. Has large knee joint effusion, clinically defined as an obvious swelling with loss of the medial sulcus as well as a ballotable patella.
4. Has another disease that can affect the health of the knee (e.g., chronic hemochromatosis; sickle cell anemia; arthropathies of systemic diseases such as chondrocalcinosis, gout, pseudogout, psoriasis, hemophilia, and infectious diseases of the joints).
5. Significant joint infection in the target knee or inflammation or skin disorder in the injection area of the target knee.
6. Fibromyalgia, anserine bursitis, lumbar radiculopathy, neurogenic or vascular claudication, vascular insufficiency of lower limbs, or peripheral neuropathy.
7. Patella femoral instability.
8. History of cartilage allograft, autograft or microfracture in the study knee.
9. Has diseases that may interfere:

1. Severe infectious disease with or without fever. COVID-19 patients will not be permitted until two negative tests are produced.
2. The history of suffering from migraine headache and requires ongoing pain medications that are prohibited per protocol.
3. Any significant chronic skin disorders, active skin or soft tissue infection that could interfere with the evaluation of the injection site.
4. Malalignment/deformity of the leg
5. Active Chronic Obstructive Pulmonary Disease (COPD) or Asthma that may require periodic treatment with steroids during the study period.
6. Active malignancy receiving treatment, or prior history of any malignancy, except for basal cell carcinoma or squamous cell carcinoma of the skin treated at least 1 year before screening.
10. Psychiatric, neurological disorders, or cognitive impairment severe enough that the individual is unable to provide informed consent, in the judgement of the Investigator.
11. Incarcerated or confined.
12. Has medical-legal, personal injury, ongoing litigation, or a worker's compensation claim(s).
13. Smokers, tobacco users and any nicotine administration through vaping or patches.
14. History of alcohol or drug abuse.
15. Received corticosteroid injection for any indication within 6 weeks prior to screening.
16. Pregnant and breast-feeding participants or planning to get pregnant during and 6 months after the study is completed.
17. Clinically significant abnormal screening laboratory results (other than those related to OA)
18. Clinically significant abnormal vital signs or physical examination findings (other than those related to OA).
19. Received hyaluronic acid treatment, Platelet rich plasma (PRP) or any other protein based or stem cells treatment, or any investigational drug within 12 weeks prior to screening.
20. Any condition that, in the opinion of the Clinical Investigator, might interfere with the evaluation of the study objectives.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled 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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
1/06/2024
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/12/2024
Actual
Sample size
Target
22
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Emeritus Research - Camberwell
Recruitment postcode(s) [1] 0 0
3124 - Camberwell

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Cytonics Corporation
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Southern Star Research Pty Ltd.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The goal of this Phase 1 study is to investigate the safety of CYT-108, our experimental recombinant protease inhibitor drug candidate for osteoarthritis, in a population of patients suffering from osteoarthritis of the knee. The main questions this study aims to answer are:

1. are two doses of CYT-108, delivered 12 weeks apart, safe when injected directly into the joint?
2. does administration of CYT-108 result in a reduction in pain, stiffness, and improvement in daily physical function?

Participants will either receive a placebo (Phosphate Buffer Saline, PBS) or CYT-108, and will be asked to report their pain/stiffness at weeks 1, 4, 8, 12, 16, and 26 (in a physician's office) after the initial injection, using a questionnaire to be provided by the physician. In addition to reporting the magnitude of pain, participants will also be asked about the onset of pain reduction. Researchers will compare the pain/stiffness scores between the CYT-108-treated to placebo-treated groups along the 26 week duration of the study. Participants will also receive blood draws along the course of the study, and researchers will analyze this blood for the presence of cartilage degradation product in attempt to identify "disease modification" (i.e., a reduction in cartilage degradation) in response to CYT-108 treatment.
Trial website
https://clinicaltrials.gov/study/NCT06263270
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Joey Bose, MS
Address 0 0
Cytonics Corporation
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Joey Bose, MS
Address 0 0
Country 0 0
Phone 0 0
4438278135
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT06263270