GAE with Embosphere Microspheres for Knee Osteoarthritis

(MOTION Trial)

Recruiting at 36 trial locations

Overseen By Ahsun Riaz, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Merit Medical Systems, Inc.

Disqualifiers: Advanced atherosclerosis, Rheumatoid arthritis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

Duration: 6 months

264 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of this drug for knee osteoarthritis?

Research shows that triamcinolone acetonide extended-release, a type of corticosteroid, significantly reduces pain and improves function in knee osteoarthritis patients compared to a placebo. It is formulated to release slowly, providing longer-lasting relief with fewer side effects. ^{1 2 3 4 5}

Is GAE with Embosphere Microspheres for Knee Osteoarthritis safe?

Triamcinolone acetonide, a type of corticosteroid used in knee osteoarthritis, is generally well tolerated with a safety profile similar to placebo, though it can cause minor side effects like hypopigmentation (lightening of the skin) and should be administered carefully to avoid tissue damage. Intra-articular corticosteroid injections are widely used and can suppress joint inflammation with minimal systemic effects, but repeated injections should be limited to avoid potential cartilage damage. ^{1 5 6 7 8}

What makes the drug GAE with Embosphere Microspheres unique for knee osteoarthritis?

This drug uses extended-release microspheres to slowly release corticosteroids directly into the knee joint, providing longer-lasting pain relief and reducing systemic side effects compared to standard corticosteroid injections. ^{5 6 9 10 11}

What is the purpose of this trial?

This multicenter, prospective, interventional trial is designed to assess the outcome of subjects with symptomatic knee osteoarthritis (OA) that are randomized to treatment with either genicular artery embolization (GAE) using Embosphere Microspheres or steroid injection over a period of 24 months.

Research Team

Sandeep Bagla, MD

Principal Investigator

Prostate Centers, USA

Craig J McAsey, MD

Principal Investigator

Anderson Orthopedic Clinic

Eligibility Criteria

This trial is for adults over 21 with knee osteoarthritis who still have pain (score of ≥4 out of 10) despite trying other treatments for at least 3 months. It's not suitable for those planning major surgeries within a month, with advanced artery disease, previous knee replacement on the affected knee, or arthritis due to rheumatoid or infection.

Inclusion Criteria

I am 21 years old or older.

My pain hasn't improved with treatment for over 3 months.

Provides written informed consent

Exclusion Criteria

I have a history of rheumatoid or infectious arthritis.

I have advanced hardening of the arteries.

I have had a knee replacement surgery on the knee in question.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to receive either genicular artery embolization using Embosphere Microspheres or corticosteroid injection for knee osteoarthritis

6 months

Multiple visits for treatment and assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

18 months

Follow-up assessments at 3, 12, and 24 months

Treatment Details

Interventions

• Corticosteroid injection
• EmboSphere Microspheres

Trial Overview The study compares two treatments for knee osteoarthritis: genicular artery embolization (GAE) using Embosphere Microspheres and steroid injections. Participants will be randomly assigned to one treatment and followed up for two years to see which is more effective.

Participant Groups

Group I: Genicular artery embolization with Embosphere Microspheres Experimental Treatment 1 Intervention

Device: Embosphere Microspheres Embolic Agent: Embosphere Microspheres

Group II: Corticosteroid Injection of the knee Active Control 1 Intervention

Drug: Corticosteroid injection

Corticosteroid injection is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Corticosteroids for:

• Allergic reactions
• Asthma
• COPD
• Rheumatoid arthritis
• Osteoarthritis
• Bursitis
• Tendonitis
• Skin conditions
• Eye conditions
• Gastrointestinal disorders

Approved in European Union as Corticosteroids for:

• Allergic reactions
• Asthma
• COPD
• Rheumatoid arthritis
• Osteoarthritis
• Bursitis
• Tendonitis
• Skin conditions
• Eye conditions
• Gastrointestinal disorders

Approved in Canada as Corticosteroids for:

• Allergic reactions
• Asthma
• COPD
• Rheumatoid arthritis
• Osteoarthritis
• Bursitis
• Tendonitis
• Skin conditions
• Eye conditions
• Gastrointestinal disorders

Who Is Running the Clinical Trial?

Merit Medical Systems, Inc.

Lead Sponsor

Trials

35

Recruited

3,500+

Findings from Research

In a double-blind study involving 30 patients with rheumatoid arthritis, all three intra-articular steroid preparations (prednisolone t-butyl acetate, methyl prednisolone acetate, and triamcinolone hexacetonide) showed thermographic improvement in knee synovitis, with triamcinolone demonstrating the greatest and longest-lasting effect.

Despite the local improvements in knee symptoms, no significant overall systemic improvement was observed after a single injection of any steroid, although all three preparations suppressed the body's natural cortisol production.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A thermographic and clinical comparison of three intra-articular steroid preparations in rheumatoid arthritis. Bird, HA., Ring, EF., Bacon, PA.[2022]

In a study of 289 rheumatoid arthritis patients, intra-articular injection of triamcinolone hexacetonide showed significant improvement in pain, particularly in patients receiving injections in the elbow and metacarpophalangeal joints, as well as those with a functional class II status.

Long-term response predictors included being male, non-white, receiving polyarticular injections, and using a higher total dose of triamcinolone, indicating that specific demographic and treatment factors can influence the effectiveness of this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Intra-articular injections of triamcinolone hexacetonide in rheumatoid arthritis: short and long-term improvement predictors]. Furtado, RN., Machado, FS., Luz, KR., et al.[2017]

Intra-articular corticosteroid injections for knee osteoarthritis showed a mild to moderate effect on pain severity lasting up to 3 months, which is longer than previously reported, based on a review of eight randomized controlled studies with follow-ups ranging from 1 to 26 weeks.

The risk of adverse effects from these injections was low, indicating that they are a relatively safe option for managing knee osteoarthritis pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Magnitude and Duration of the Effect of Intra-articular Corticosteroid Injections on Pain Severity in Knee Osteoarthritis: A Systematic Review and Meta-Analysis. Saltychev, M., Mattie, R., McCormick, Z., et al.[2021]

In a study of 79 children with juvenile chronic arthritis, triamcinolone injections were found to significantly improve the likelihood of remission compared to methylprednisolone, with results showing a strong statistical significance (p < 0.0005).

The length of remission was associated with the proportion of polymorphonuclear leucocytes in the synovial fluid, indicating that patients with lower levels of these cells experienced longer remissions, suggesting a potential biomarker for treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intra-articular glucocorticoids in early juvenile chronic arthritis. Honkanen, VE., Rautonen, JK., Pelkonen, PM.[2019]

Triamcinolone acetonide extended-release (ER) 32 mg significantly reduces knee osteoarthritis pain over 24 weeks compared to placebo, while also improving stiffness and physical function, demonstrating its efficacy as a treatment option.

The formulation of triamcinolone acetonide ER in PLGA microspheres allows for prolonged release in the joint, minimizing systemic exposure and related side effects, making it a safer alternative to traditional corticosteroid injections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Triamcinolone Acetonide Extended-Release: A Review in Osteoarthritis Pain of the Knee. Paik, J., Duggan, ST., Keam, SJ.[2023]

In a study involving 7 patients with osteoarthritis, both prednisolone tebuate and triamcinolone hexacetonide were injected into knee joints, revealing that most patients experienced an increase in synovial fluid leukocyte counts, indicating some inflammatory response.

Electron microscopy (EM) successfully identified corticosteroid crystals in the joint fluid 24 hours and 1 week post-injection, providing a valuable method for distinguishing these crystals from others, which could enhance the understanding of corticosteroid behavior in the body.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electron microscopic study of depot corticosteroid crystals with clinical studies after intra-articular injection. Gordon, GV., Schumacher, HR.[2013]

Intra-articular injections of triamcinalone acetonide, a common glucocorticoid, can lead to cutaneous hypopigmentation, which is a rare but notable side effect.

This case highlights a unique pattern of hypopigmentation with a linear ray distribution, suggesting that the glucocorticoid may spread through lymphatic channels after injection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Linear rays of hypopigmentation following intra-articular corticosteroid injection for post-traumatic degenerative joint disease. Schwartz, C., Javvaji, S., Feinberg, JS.[2013]

Intra-articular glucocorticosteroid injections, particularly with triamcinolone hexacetonide, can effectively reduce joint inflammation in conditions like rheumatoid arthritis and osteoarthritis, providing rapid relief with minimal systemic side effects.

However, these injections should be administered cautiously by experienced clinicians due to risks such as local tissue necrosis and potential cartilage damage, with recommendations to limit injections to no more than three or four per year in the same joint.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Intra-articular glucocorticoid injections in joint diseases]. Ostergaard, M., Halberg, P.[2017]

A single intra-articular injection of triamcinolone acetonide extended-release (TA-ER) showed prolonged presence in the joint compared to the standard crystalline suspension, indicating its potential for sustained therapeutic effects in knee osteoarthritis.

The study found that while TA-ER and the crystalline form had similar mild effects on cartilage, the transient nature of these effects suggests that TA-ER's benefits may be more pronounced in diseased joints rather than in healthy ones.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Local Effects Following Single and Repeat Intra-Articular Injections of Triamcinolone Acetonide Extended-Release: Results from Three Nonclinical Toxicity Studies in Dogs. Bodick, N., Williamson, T., Strand, V., et al.[2020]

The extended-release formulation of triamcinolone acetonide (FX006) provided prolonged synovial fluid residency in knee osteoarthritis patients, maintaining therapeutic levels for up to 12 weeks, compared to the crystalline suspension (TAcs) which had minimal presence by Week 6.

FX006 resulted in lower peak plasma levels of the drug, reducing systemic exposure and potential side effects, while both formulations had similar safety profiles in terms of adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synovial and systemic pharmacokinetics (PK) of triamcinolone acetonide (TA) following intra-articular (IA) injection of an extended-release microsphere-based formulation (FX006) or standard crystalline suspension in patients with knee osteoarthritis (OA). Kraus, VB., Conaghan, PG., Aazami, HA., et al.[2018]

In a study of 20 patients with rheumatoid arthritis, post-injection rest did not significantly affect the resorption of the glucocorticoid triamcinolone hexacetonide (THA) after intra-articular administration, as serum levels peaked similarly in both resting and active groups.

Both resting and mobile patients experienced short-term decreases in serum cortisol and ACTH levels, indicating a temporary suppression of the hypothalamic-pituitary-adrenal axis, but this effect was not influenced by the level of activity after the injection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glucocorticoid resorption and influence on the hypothalamic-pituitary-adrenal axis after intra-articular treatment of the knee in resting and mobile patients. Weitoft, T., Rönnblom, L.[2018]

References

1. England pubmed.ncbi.nlm.nih.gov

A thermographic and clinical comparison of three intra-articular steroid preparations in rheumatoid arthritis. [2022]

2. Brazil pubmed.ncbi.nlm.nih.gov

[Intra-articular injections of triamcinolone hexacetonide in rheumatoid arthritis: short and long-term improvement predictors]. [2017]

3. United States pubmed.ncbi.nlm.nih.gov

The Magnitude and Duration of the Effect of Intra-articular Corticosteroid Injections on Pain Severity in Knee Osteoarthritis: A Systematic Review and Meta-Analysis. [2021]

4. Norway pubmed.ncbi.nlm.nih.gov

Intra-articular glucocorticoids in early juvenile chronic arthritis. [2019]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Triamcinolone Acetonide Extended-Release: A Review in Osteoarthritis Pain of the Knee. [2023]

6. Canada pubmed.ncbi.nlm.nih.gov

Electron microscopic study of depot corticosteroid crystals with clinical studies after intra-articular injection. [2013]

7. United States pubmed.ncbi.nlm.nih.gov

Linear rays of hypopigmentation following intra-articular corticosteroid injection for post-traumatic degenerative joint disease. [2013]

8. Denmark pubmed.ncbi.nlm.nih.gov

[Intra-articular glucocorticoid injections in joint diseases]. [2017]

9. England pubmed.ncbi.nlm.nih.gov

Local Effects Following Single and Repeat Intra-Articular Injections of Triamcinolone Acetonide Extended-Release: Results from Three Nonclinical Toxicity Studies in Dogs. [2020]

10. England pubmed.ncbi.nlm.nih.gov

Synovial and systemic pharmacokinetics (PK) of triamcinolone acetonide (TA) following intra-articular (IA) injection of an extended-release microsphere-based formulation (FX006) or standard crystalline suspension in patients with knee osteoarthritis (OA). [2018]

11. England pubmed.ncbi.nlm.nih.gov

Glucocorticoid resorption and influence on the hypothalamic-pituitary-adrenal axis after intra-articular treatment of the knee in resting and mobile patients. [2018]