Osteoarthritis, KneePhase 1NCT06263270
Evaluation of CYT-108, A Recombinant Protease Inhibitor, for Treatment of Mild To Moderate Primary Osteoarthritis Of The Knee
A Phase 1 study testing CYT-108, a recombinant protease inhibitor and Phosphate Buffered Saline (PBS) in people with Osteoarthritis, Knee and Osteoarthritis, run by Cytonics Corporation at 3 sites in Australia.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Osteoarthritis, Knee, Osteoarthritis
- What is being tested?
- CYT-108, a recombinant protease inhibitor and Phosphate Buffered Saline (PBS)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 19 participants
- Where
- 3 sitesAustralia
- Study dates
- 1 Jun 2024to 10 Oct 2025
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participant with mild to moderate primary knee OA.
- Provides signed written informed consent before any study procedure is performed.
- Is willing and able to complete effectiveness and safety questionnaires and can read and understand study instructions.
- Adult aged 18 years or older at the time of informed consent.
- 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.
- 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).
Show all 13Show fewer
- Is ambulatory (assistive devices or knee braces are allowed if used during the study).
- 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.
- Remains symptomatic despite having received standard of- care therapy, such as daily doses of NSAID or any pain medication leading to the study screening.
- Has not received corticosteroid injection within 6 weeks prior to screening.
- 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.
Who cannot join
- Any of the following:
- Grade 4 score on the K-L grading scale for the target knee
- 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)
- Acute fracture of the lower limb
- Participant with OA in both knees.
- Medical history of severe bone disease (e.g., osteoporosis, osteonecrosis, joint deformity, instability, or septic arthritis).
Show all 30Show fewer
- Has large knee joint effusion, clinically defined as an obvious swelling with loss of the medial sulcus as well as a ballotable patella.
- 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).
- Significant joint infection in the target knee or inflammation or skin disorder in the injection area of the target knee.
- Fibromyalgia, anserine bursitis, lumbar radiculopathy, neurogenic or vascular claudication, vascular insufficiency of lower limbs, or peripheral neuropathy.
- Patella femoral instability.
- History of cartilage allograft, autograft or microfracture in the study knee.
- Has diseases that may interfere:
- Severe infectious disease with or without fever. COVID-19 patients will not be permitted until two negative tests are produced.
- The history of suffering from migraine headache and requires ongoing pain medications that are prohibited per protocol.
- Any significant chronic skin disorders, active skin or soft tissue infection that could interfere with the evaluation of the injection site.
- Malalignment/deformity of the leg
- Active Chronic Obstructive Pulmonary Disease (COPD) or Asthma that may require periodic treatment with steroids during the study period.
- 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.
- Psychiatric, neurological disorders, or cognitive impairment severe enough that the individual is unable to provide informed consent, in the judgement of the Investigator.
- Incarcerated or confined.
- Has medical-legal, personal injury, ongoing litigation, or a worker's compensation claim(s).
- Smokers, tobacco users and any nicotine administration through vaping or patches.
- History of alcohol or drug abuse.
- Received corticosteroid injection for any indication within 6 weeks prior to screening.
- Pregnant and breast-feeding participants or planning to get pregnant during and 6 months after the study is completed.
- Clinically significant abnormal screening laboratory results (other than those related to OA)
- Clinically significant abnormal vital signs or physical examination findings (other than those related to OA).
- 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.
- Any condition that, in the opinion of the Clinical Investigator, might interfere with the evaluation of the study objectives.
Trial locations and contacts
3 sites in 1 country.
Australia3 sites
Emeritus Research
Camberwell, Victoria, 3124
Novatrials
Kotara, New South Wales, 2289
University of Sunshine Coast Clinical Trials
Sunshine Coast, Birtinya QLD, 4575
About this study
Official 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
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:
- are two doses of CYT-108, delivered 12 weeks apart, safe when injected directly into the joint?
- 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.
Read the detailed description
The Phase 1a trial will be a multicenter, double-blind, randomized, placebo-controlled clinical study to evaluate the safety of two doses of CYT-108 (given at Day 1 and Day 85) in participants with mild to moderate primary OA of the knee, followed out to 26 weeks. A Screening Visit will be performed between twenty-eight days to two days before the first dose, (i.e., Days -28 to -2), and if eligible, participants will attend baseline evaluation on Day 1 to confirm eligibility before randomization to treatment. The first and second doses will be administered on Day 1 and Day 85 (12 weeks post-first dose, with six follow-up visits on Days 8, 29, 57, 85, 113, and 183 (1, 4, 8, 12, 16, and 26 weeks post-first dose respectively).
At screening, each participant will undergo the informed consent process. After written informed consent is obtained, participants will undergo screening assessments to determine study eligibility. Participants who have not had an X-ray performed within 6 months of screening will undergo an X-ray to determine eligibility. After completing all assessments and meeting study eligibility, the participant will be randomized to receive active treatment or control. Assessments of OA symptoms (WOMAC) will be performed, and blood samples will be obtained at screening and the baseline visit pre-first dose (Day 1) and at specified time-points over the 26-week study period (Weeks 1, 4, 8, 12, 16, and 26).
Approximately twenty-two (22) participants will be randomized in this study in the following manner:
- Participants randomized to Active treatment (12 participants, to assure at least 10 participants to complete the study) will receive one, 5mL (five milliliters) intra-articular injections of CYT-108 (5mg/mL) on each Days 1 and 85, with arthrocentesis prior to injection if clinically appropriate at the time of intervention. Excess fluid in the participant's knee joint will be withdrawn before the drug injection and discarded.
- Participants randomized to Control treatment (10 participants) will receive one, 5mL intra-articular injections of PBS on each Days 1 and 85, with arthrocentesis prior to injection if clinically appropriate at the time of intervention. Excess fluid in the participant's knee joint will be withdrawn before the drug injection and discarded.
Following screening, all participants will have seven site visits on schedule starting with attending the site for the first injection on Day 1, with follow up visits at Weeks 1, 4, 8 and 12. The second injection will be administered at Week 12 after the Investigator has reviewed the participant and confirmed administration of the second dose is acceptable. After this second dose, follow-up evaluations will be conducted in Weeks 16, and 26. At each visit, patients will a combination of physical exams, blood draws, urinalysis, analysis of vital signs, and joint pain/stiffness assessment (using the WOMAC scoring system).
The Week 26 visit will be the end of the study visit (EOS). Participants who withdraw or are withdrawn after the first dose will be asked to attend at early termination visit (ET), at which EOS assessments will be performed. Self-provided rescue medication and any other concomitant medication will be recorded throughout the duration of the study by the study staff or via the participant's diary (ePRO).
- Conditions
- Osteoarthritis, Knee, Osteoarthritis
- Being tested
- CYT-108, a recombinant protease inhibitor, Phosphate Buffered Saline (PBS)
- Keywords
- arthritis, osteoarthritis, joint pain, joint inflammation, knee
- Medical subject headings
- Osteoarthritis, Knee, Osteoarthritis, Arthritis, Arthralgia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CYT-108, a recombinant protease inhibitorBiological
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.
Phosphate Buffered Saline (PBS)Other
Phosphate Buffered Saline (PBS)
| Study group | Role | What they receive |
|---|---|---|
| Active Treatment Arm (CYT-108) | Active comparator | 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). Receives: Biological: CYT-108, a recombinant protease inhibitor |
| Placebo Control Arm (Phosphate Buffered Saline) | Placebo comparator | 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. Receives: Other: Phosphate Buffered Saline (PBS) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse Events
Frequency and severity of Adverse Events (AE), Serious Adverse, Events (SAE) and Treatment-Emergent Adverse Events (TEAEs).
Measured: Day 0; Weeks 1, 4, 8, 12, 16, 26
Blood Pressure
Systolic and Diastolic blood pressure [mmHg]
Measured: Day 0; Weeks 1, 4, 8, 12, 16, 26
Heart Rate
Heart rate [beats per minute]
Measured: Day 0; Weeks 1, 4, 8, 12, 16, 26
Respiratory Rate
Respiratory rate [breaths per minute]
Measured: Day 0; Weeks 1, 4, 8, 12, 16, 26
Body Temperature
Body temperature [°C]
Measured: Day 0; Weeks 1, 4, 8, 12, 16, 26
Titer of Human Anti-Drug Antibody
Change from baseline in human anti-drug antibody (HADA) to evaluate the immune response toward the new bait region of the molecule (assay to be developed).
Measured: Day 0; Weeks 1, 4, 8, 12, 16, 26
Secondary outcomes (2)
Change in WOMAC Scores (Pain, Stiffness, and Difficulty Performing Daily Activities)
Changes in pain, stiffness, and difficultly in performing daily activities in the treatment group will be compared to the control group using participant's own assessment at 1, 4, 8, 12, 16, and 26 weeks after first intra-articular injection of CYT-108 into the target knee, as determined by the Western Ontario and McMaster Universities Osteoarthritis Index NRS 3.1 (WOMAC). The WOMAC is divided into three subscales: WOMAC-A (pain, 5 questions, 0-10), WOMAC-B (stiffness, 2 questions, 0-10), and WOMAC-C (daily physical function, 17 questions, 0-10). The WOMAC total score ranges from 0-240, where a higher score indicates a worse outcome.
Measured: Day 0; Weeks 1, 4, 8, 12, 16, 26
Time of Onset
Time of onset of pain determined by asking enrolled participants whether they are aware of the onset of meaningful pain reduction and the time it took for the pain reduction
Measured: Day 0; Weeks 1, 4, 8, 12, 16, 26
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Feb 2024
- Study start1 Jun 2024
- Primary completion15 Mar 2025
- Study completion10 Oct 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Osteoarthritis, KneeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The Phase 1a trial will be a multicenter, double-blind, randomized, placebo-controlled clinical study to evaluate the safety of two doses of CYT-108 (given at Day 1 and Day 85) in participants with mild to moderate primary OA of the knee, followed out to 26 weeks. A Screening Visit will be performed between twenty-eight days to two days before the first dose, (i.e., Days -28 to -2), and if eligible, participants will attend baseline evaluation on Day 1 to confirm eligibility before randomisation to treatment. The first and second doses will be administered on Day 1 and Day 85 (12 weeks post-first dose, with six follow-up visits on Days 8, 29, 57, 85, 113, and 183; Weeks 1, 4, 8, 12, 16, and 26 weeks post-first dose respectively).
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cytonics Corporation
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Joey Bose, MS, Study director, Cytonics CorporationLewis Hanna, PhD, Study director, Cytonics CorporationGaetano Scuderi, MD, Study director, Cytonics Corporation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06263270
- Sponsor's protocol ID
- 12-2023-01
- Status last verified
- Dec 2025
- First submitted
- 10 Jan 2024
- Last updated
- 26 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT06263270
- Acronym / sponsor ID
- 12-2023-01
- Conditions
- Osteoarthritis, Knee, Osteoarthritis
- Keywords
- arthritis, osteoarthritis, joint pain, joint inflammation, knee
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Cytonics CorporationIndustry (pharma, biotech, devices)
- Study start
- 1 Jun 2024 (actual)
- Primary completion
- 15 Mar 2025 (actual)
- Study completion
- 10 Oct 2025 (actual)
- First posted
- 16 Feb 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- are two doses of CYT-108, delivered 12 weeks apart, safe when injected directly into the joint?
- 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.
Detailed description
The Phase 1a trial will be a multicenter, double-blind, randomized, placebo-controlled clinical study to evaluate the safety of two doses of CYT-108 (given at Day 1 and Day 85) in participants with mild to moderate primary OA of the knee, followed out to 26 weeks. A Screening Visit will be performed between twenty-eight days to two days before the first dose, (i.e., Days -28 to -2), and if eligible, participants will attend baseline evaluation on Day 1 to confirm eligibility before randomization to treatment. The first and second doses will be administered on Day 1 and Day 85 (12 weeks post-first dose, with six follow-up visits on Days 8, 29, 57, 85, 113, and 183 (1, 4, 8, 12, 16, and 26 weeks post-first dose respectively).
At screening, each participant will undergo the informed consent process. After written informed consent is obtained, participants will undergo screening assessments to determine study eligibility. Participants who have not had an X-ray performed within 6 months of screening will undergo an X-ray to determine eligibility. After completing all assessments and meeting study eligibility, the participant will be randomized to receive active treatment or control. Assessments of OA symptoms (WOMAC) will be performed, and blood samples will be obtained at screening and the baseline visit pre-first dose (Day 1) and at specified time-points over the 26-week study period (Weeks 1, 4, 8, 12, 16, and 26).
Approximately twenty-two (22) participants will be randomized in this study in the following manner:
- Participants randomized to Active treatment (12 participants, to assure at least 10 participants to complete the study) will receive one, 5mL (five milliliters) intra-articular injections of CYT-108 (5mg/mL) on each Days 1 and 85, with arthrocentesis prior to injection if clinically appropriate at the time of intervention. Excess fluid in the participant's knee joint will be withdrawn before the drug injection and discarded.
- Participants randomized to Control treatment (10 participants) will receive one, 5mL intra-articular injections of PBS on each Days 1 and 85, with arthrocentesis prior to injection if clinically appropriate at the time of intervention. Excess fluid in the participant's knee joint will be withdrawn before the drug injection and discarded.
Following screening, all participants will have seven site visits on schedule starting with attending the site for the first injection on Day 1, with follow up visits at Weeks 1, 4, 8 and 12. The second injection will be administered at Week 12 after the Investigator has reviewed the participant and confirmed administration of the second dose is acceptable. After this second dose, follow-up evaluations will be conducted in Weeks 16, and 26. At each visit, patients will a combination of physical exams, blood draws, urinalysis, analysis of vital signs, and joint pain/stiffness assessment (using the WOMAC scoring system).
The Week 26 visit will be the end of the study visit (EOS). Participants who withdraw or are withdrawn after the first dose will be asked to attend at early termination visit (ET), at which EOS assessments will be performed. Self-provided rescue medication and any other concomitant medication will be recorded throughout the duration of the study by the study staff or via the participant's diary (ePRO).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- The Phase 1a trial will be a multicenter, double-blind, randomized, placebo-controlled clinical study to evaluate the safety of two doses of CYT-108 (given at Day 1 and Day 85) in participants with mild to moderate primary OA of the knee, followed out to 26 weeks. A Screening Visit will be performed between twenty-eight days to two days before the first dose, (i.e., Days -28 to -2), and if eligible, participants will attend baseline evaluation on Day 1 to confirm eligibility before randomisation to treatment. The first and second doses will be administered on Day 1 and Day 85 (12 weeks post-first dose, with six follow-up visits on Days 8, 29, 57, 85, 113, and 183; Weeks 1, 4, 8, 12, 16, and 26 weeks post-first dose respectively).
| Arm | Type | Receives |
|---|---|---|
| Active Treatment Arm (CYT-108) | Active comparator | Biological: CYT-108, a recombinant protease inhibitorOne 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 Control Arm (Phosphate Buffered Saline) | Placebo comparator | Other: Phosphate Buffered Saline (PBS)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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Participant with mild to moderate primary knee OA.
- Provides signed written informed consent before any study procedure is performed.
- Is willing and able to complete effectiveness and safety questionnaires and can read and understand study instructions.
- Adult aged 18 years or older at the time of informed consent.
- 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.
Key exclusion criteria (30 listed)
- Any of the following:
- Medical history of severe bone disease (e.g., osteoporosis, osteonecrosis, joint deformity, instability, or septic arthritis).
- Has large knee joint effusion, clinically defined as an obvious swelling with loss of the medial sulcus as well as a ballotable patella.
- 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).
- Significant joint infection in the target knee or inflammation or skin disorder in the injection area of the target knee.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CYT-108, a recombinant protease inhibitorCYT-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. | Biological | Active Treatment Arm (CYT-108) |
| Phosphate Buffered Saline (PBS)Phosphate Buffered Saline (PBS) | Other | Placebo Control Arm (Phosphate Buffered Saline) |
Primary outcome
Adverse Events
Time frame: Day 0; Weeks 1, 4, 8, 12, 16, 26
Frequency and severity of Adverse Events (AE), Serious Adverse, Events (SAE) and Treatment-Emergent Adverse Events (TEAEs).
Blood Pressure
Time frame: Day 0; Weeks 1, 4, 8, 12, 16, 26
Systolic and Diastolic blood pressure [mmHg]
Heart Rate
Time frame: Day 0; Weeks 1, 4, 8, 12, 16, 26
Heart rate [beats per minute]
Respiratory Rate
Time frame: Day 0; Weeks 1, 4, 8, 12, 16, 26
Respiratory rate [breaths per minute]
Body Temperature
Time frame: Day 0; Weeks 1, 4, 8, 12, 16, 26
Body temperature [°C]
Titer of Human Anti-Drug Antibody
Time frame: Day 0; Weeks 1, 4, 8, 12, 16, 26
Change from baseline in human anti-drug antibody (HADA) to evaluate the immune response toward the new bait region of the molecule (assay to be developed).
2 secondary outcomes
Change in WOMAC Scores (Pain, Stiffness, and Difficulty Performing Daily Activities)
Time frame: Day 0; Weeks 1, 4, 8, 12, 16, 26
Time of Onset
Time frame: Day 0; Weeks 1, 4, 8, 12, 16, 26
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Dec 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Joey Bose, MS study director
Cytonics Corporation
Lewis Hanna, PhD study director
Cytonics Corporation
Gaetano Scuderi, MD study director
Cytonics Corporation
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CYT-108, a recombinant protease inhibitor and Phosphate Buffered Saline (PBS) in people with Osteoarthritis, Knee and Osteoarthritis, run by Cytonics Corporation at 3 sites in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adverse Events (time frame: Day 0; Weeks 1, 4, 8, 12, 16, 26). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Dec 2025.