Evaluation of CYT-108, A Recombinant Protease Inhibitor, for Treatment of Mild To Moderate Primary Osteoarthritis Of The Knee

NCT06263270 | Completed Phase 1 DMC

• 1 other identifier: 12-2023-01
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 3

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

Conditions

Osteoarthritis; Osteoarthritis, Knee

Keywords

arthritis; osteoarthritis; joint pain; joint inflammation; knee

Outcome Measures

Primary Outcomes (6)

• Adverse Events

  Frequency and severity of Adverse Events (AE), Serious Adverse, Events (SAE) and Treatment-Emergent Adverse Events (TEAEs).

  Day 0; Weeks 1, 4, 8, 12, 16, 26

• Blood Pressure

  Systolic and Diastolic blood pressure \[mmHg\]

  Day 0; Weeks 1, 4, 8, 12, 16, 26

• Heart Rate

  Heart rate \[beats per minute\]

  Day 0; Weeks 1, 4, 8, 12, 16, 26

• Respiratory Rate

  Respiratory rate \[breaths per minute\]

  Day 0; Weeks 1, 4, 8, 12, 16, 26

• Body Temperature

  Body temperature \[°C\]

  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).

  Day 0; Weeks 1, 4, 8, 12, 16, 26

Secondary Outcomes (2)

• Change in WOMAC Scores (Pain, Stiffness, and Difficulty Performing Daily Activities)

  Day 0; Weeks 1, 4, 8, 12, 16, 26

• Time of Onset

  Day 0; Weeks 1, 4, 8, 12, 16, 26

Other Outcomes (1)

• Concentration of Cartilage Degradation Fragments in Blood Plasma

  Day 0; Weeks 1, 4, 8, 12, 16, 26

Study Arms (2)

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).

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.

Other: Phosphate Buffered Saline (PBS)

Interventions

CYT-108, a recombinant protease inhibitor BIOLOGICAL

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.

Active Treatment Arm (CYT-108)

Phosphate Buffered Saline (PBS) OTHER

Phosphate Buffered Saline (PBS)

Placebo Control Arm (Phosphate Buffered Saline)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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.

You may not qualify if:

• 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).
• 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.

Sponsors & Collaborators

• Cytonics Corporation: lead

Study Sites (3)

University of Sunshine Coast Clinical Trials

Sunshine Coast, Birtinya QLD, 4575, Australia

Location

Novatrials

Kotara, New South Wales, 2289, Australia

Location

Emeritus Research

Camberwell, Victoria, 3124, Australia

Location

MeSH Terms

Conditions

Osteoarthritis, Knee; Osteoarthritis; Arthritis; Arthralgia

Condition Hierarchy (Ancestors)

Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Joey Bose, MS

  Cytonics Corporation

  STUDY DIRECTOR

• Lewis Hanna, PhD

  Cytonics Corporation

  STUDY DIRECTOR

• Gaetano Scuderi, MD

  Cytonics Corporation

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This study is double-blind, placebo-controlled. Neither the investigator, care providers, patients, nor study sponsor have knowledge of the interventions assigned to each participant.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: January 10, 2024
• First Posted: February 16, 2024
• Study Start: June 1, 2024
• Primary Completion: March 15, 2025
• Study Completion: October 10, 2025
• Last Updated: December 26, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

AU (3)