ZILRETTA for Shoulder Osteoarthritis

Recruiting at 37 trial locations

Overseen By Jack Castaneda

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Pacira Pharmaceuticals, Inc

Must not be taking: Opioids, Analgesics, THC/CBD, SSRIs/SNRIs

Disqualifiers: Symptomatic arthritis, Rotator cuff pathology, Chronic shoulder pain, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 10

Duration: Single day (Baseline/Day 1)

150 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of ZILRETTA in relieving shoulder pain caused by osteoarthritis (OA). Participants will receive an injection of either ZILRETTA, a common steroid treatment called TCA-IR, or a placebo (a non-active substance) to compare their effects. The main goal is to determine if ZILRETTA reduces pain more effectively than the other options. This trial may suit individuals who have experienced shoulder pain from OA for over three months and feel discomfort more than 15 days a month. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial requires participants to stop taking certain medications, such as opioids, other pain relievers, and products containing THC or CBD. If you are on these or other restricted medications, you may need to stop them before joining the study.

Is there any evidence suggesting that ZILRETTA is likely to be safe for humans?

Research has shown that ZILRETTA, a treatment for osteoarthritis, is generally safe. In earlier studies, ZILRETTA, a long-acting form of the steroid triamcinolone acetonide, released the medication slowly and steadily, helping to reduce side effects.

These studies also found no major safety differences between older and younger patients, which is reassuring. This indicates that ZILRETTA is usually well-tolerated by people of different ages.

ZILRETTA has already received FDA approval for treating knee osteoarthritis, which adds to its safety credibility. However, individual experiences can vary, so discussing any concerns with a healthcare provider is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for osteoarthritis?

ZILRETTA is unique because it is a long-acting corticosteroid specifically formulated for osteoarthritis of the shoulder. Unlike standard treatments that often involve oral medications or immediate-release injections, ZILRETTA uses a special extended-release technology that allows the medication to gradually deliver its effects over time, potentially providing longer-lasting relief from pain. Researchers are excited about ZILRETTA because this sustained action could mean fewer injections are needed, offering a more convenient option for patients while maintaining effective pain management.

What evidence suggests that ZILRETTA might be an effective treatment for shoulder osteoarthritis?

Research has shown that ZILRETTA, which participants in this trial may receive, can significantly relieve pain for people with osteoarthritis. In earlier studies, patients who received a ZILRETTA injection experienced less pain for up to 24 weeks compared to those who received a placebo. This treatment works by slowly releasing medication over time, helping to manage pain for a longer period. Results for treating shoulder arthritis mirror those for knee arthritis, indicating effectiveness across different joints. Overall, evidence supports ZILRETTA's potential to reduce pain in people with shoulder osteoarthritis. ^{1 2 4 6 7}

Who Is on the Research Team?

Nino Joy, MD

Principal Investigator

Pacira Pharmaceuticals, Inc

Are You a Good Fit for This Trial?

This trial is for individuals with shoulder osteoarthritis, specifically in the glenohumeral joint. Participants should have a history of pain due to their condition and be suitable candidates for intra-articular injection treatments.

Inclusion Criteria

I have had shoulder pain or symptoms for 3 months or more.

I am using or willing to use effective birth control during the study.

Body Mass Index (BMI) ≤40 kg/m2

Exclusion Criteria

I have shoulder pain or damage due to a rotator cuff issue.

I had a shoulder or upper arm bone fracture in the last 2 years.

I had a shoulder injury that limited my movement for over a month.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

10-35 days

1 visit (in-person)

Pre-treatment

Participants undergo pre-treatment assessments and training, including eDiary registration and training for accurate pain reporting

Up to 35 days

Treatment

Participants receive a single intra-articular injection of either ZILRETTA, TCA-IR, or placebo

Single day (Baseline/Day 1)

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness with outpatient visits and daily eDiary entries

24 weeks

8 visits (in-person) at Weeks 2, 4, 8, 12, 16, 18, 20, and 24

What Are the Treatments Tested in This Trial?

Interventions

• TCA-IR
• ZILRETTA

Trial Overview The study aims to compare the effectiveness and safety of ZILRETTA (an extended-release corticosteroid) against a placebo (normal saline) and an immediate-release steroid (TCA-IR), all administered through single-dose injections directly into the shoulder joint.

How Is the Trial Designed?

Group I: ZILRETTA Experimental Treatment 1 Intervention

100 subjects will receive 32 mg ZILRETTA

Group II: Placebo Placebo Group 1 Intervention

50 subjects will receive normal saline placebo

ZILRETTA is already approved in United States for the following indications:

Approved in United States as ZILRETTA for:

• Osteoarthritis pain of the knee

Who Is Running the Clinical Trial?

Pacira Pharmaceuticals, Inc

Lead Sponsor

Trials

142

Recruited

14,300+

Headquarters

Tampa, USA

Known For

Non-opioid Pain Management

Top Products

Exparel, Zilretta, iovera

Dr. Jonathan Slonin

Pacira Pharmaceuticals, Inc

Chief Medical Officer since 2020

BSc in Biomedical Engineering and MD from University of Miami, MBA from George Washington University

Frank D. Lee

Pacira Pharmaceuticals, Inc

Chief Executive Officer since 2024

BSc in Chemical Engineering from Vanderbilt University, MBA from Wharton Graduate School of Business

Published Research Related to This Trial

In a study involving 84 patients with adhesive capsulitis, both 40 mg and 10 mg doses of triamcinolone acetonide (TA) used in ultrasound-guided hydrodilatation showed similar improvements in shoulder pain, disability, and range of motion over 12 weeks.

Given that both doses were equally effective and no adverse events were reported, using the lower dose of 10 mg TA may be preferable to minimize potential negative effects on surrounding cartilage and tendons.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Effectiveness of Corticosteroid Dosages for Ultrasound-Guided Glenohumeral Joint Hydrodilatation in Adhesive Capsulitis: A Randomized Controlled Trial. Wang, JC., Hsu, PC., Wang, KA., et al.[2023]

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 of 135 patients with frozen shoulder, both triamcinolone acetonide and methylprednisolone acetate were found to be equally effective for primary frozen shoulder, with success rates of 81.8% and 83.3%, respectively.

Triamcinolone acetonide was particularly effective for diabetic frozen shoulder, showing a significant improvement rate of 69% compared to 39% for methylprednisolone acetate, and required fewer injections for similar or better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison between intraarticular triamcinolone acetonide and methylprednisolone acetate injections in treatment of frozen shoulder. Sakeni, RA., Al-Nimer, MS.[2018]

In a study of 26 patients with frozen shoulder syndrome, those receiving a 40 mg intra-articular injection of triamcinolone had a 'cured' rate 5.8 times higher after one week compared to those taking oral triamcinolone tablets.

Sixty-two percent of patients in the injection group achieved a 'cured' condition within a week, while only 14% in the oral tablet group did, indicating that intra-articular corticosteroid injections provide faster relief from symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Frozen shoulder syndrome: comparison of oral route corticosteroid and intra-articular corticosteroid injection. Widiastuti-Samekto, M., Sianturi, GP.[2013]

In a study involving 30 patients with hip osteoarthritis, the extended-release formulation of triamcinolone acetonide (TA-ER) was found to have a comparable safety profile to the conventional crystalline suspension (TAcs), with fewer treatment-emergent adverse events (TEAEs) reported (26.7% for TA-ER vs. 46.7% for TAcs).

TA-ER resulted in significantly lower peak plasma concentrations and overall systemic exposure compared to TAcs, suggesting a potentially safer profile with gradual elimination from the body, which may reduce the risk of systemic side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized, Open-Label, Single-Dose Study to Assess Safety and Systemic Exposure of Triamcinolone Acetonide Extended-Release in Patients With Hip Osteoarthritis. Kivitz, A., Mehra, P., Hanson, P., et al.[2022]

Triamcinolone acetonide (TA) loaded polycaprolactone (PCL) implants can effectively release the drug over 180 days, with filament-shaped implants showing the highest release rate, which could improve treatment for eye diseases while reducing the need for frequent injections.

The implants demonstrated over 90% cell viability in biocompatibility studies, indicating they are safe for use in ocular applications, potentially enhancing patient compliance and reducing side effects associated with traditional intravitreal injections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fabrication and Characterisation of 3D-Printed Triamcinolone Acetonide-Loaded Polycaprolactone-Based Ocular Implants. Annuryanti, F., Domínguez-Robles, J., Anjani, QK., et al.[2023]

In a Phase-3 study involving 484 adults with knee osteoarthritis, FX006 (32 mg) significantly reduced average daily pain intensity compared to saline placebo, achieving about a 50% improvement by week 12.

FX006 also showed favorable results in secondary and exploratory measures of osteoarthritis symptoms compared to placebo, while its efficacy was similar to that of standard triamcinolone acetonide (TAcs) in terms of pain reduction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of a Single Intra-Articular Injection of a Microsphere Formulation of Triamcinolone Acetonide on Knee Osteoarthritis Pain: A Double-Blinded, Randomized, Placebo-Controlled, Multinational Study. Conaghan, PG., Hunter, DJ., Cohen, SB., et al.[2019]

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]

In a phase 2 study involving 25 patients with shoulder osteoarthritis, triamcinolone acetonide extended-release (TA-ER) demonstrated a lower systemic exposure compared to the crystalline suspension (TAcs), suggesting a potentially improved safety profile for TA-ER.

Both formulations were well-tolerated, with no serious adverse events reported, indicating that TA-ER may provide effective treatment with reduced risk of systemic side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Systemic Exposure of Triamcinolone Acetonide Following Ultrasound-Guided Intra-Articular Injection of Triamcinolone Extended-Release or Standard Triamcinolone Acetonide in Patients with Shoulder Osteoarthritis: An Open-Label, Randomized Study. Hanson, P., Kivitz, A., Mehra, P., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8363704/

Safety and Systemic Exposure of Triamcinolone Acetonide ... These pharmacokinetic data confirm protracted release of TA from TA-ER following IA injection in patients with shoulder OA. Lower peak and systemic TA exposure ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6437125/

Triamcinolone Acetonide Extended-Release: A Review in ... Although triamcinolone acetonide ER showed significant improvements in pain relief relative to placebo after 24 weeks following treatment with ...

3. zilrettapro.com zilrettapro.com/efficacy

ZILRETTA® Efficacy Data | Clinical Trial Results Review ZILRETTA clinical trial design and study outcomes. Access efficacy data and research information for healthcare providers.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06269705

Study Details | NCT06269705 | ZILRETTA in Subjects With ... This is a multi-center, randomized, double-blind, parallel-group study to evaluate the efficacy and safety of ZILRETTA in subjects with glenohumeral OA.

5. biospace.com biospace.com/flexion-therapeutics-announces-publication-of-results-from-phase-2-pharmacokinetics-pk-and-safety-study-of-zilretta-in-shoulder-osteoarthritis-oa

Flexion Therapeutics Announces Publication of Results ... “The publication of these data demonstrate that ZILRETTA's release profile in the shoulder is consistent with what we observed in the knee, and ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2017/208845s000lbl.pdf

4163229 This label may not be the latest approved by FDA ... No overall differences in safety or effectiveness were observed between elderly and younger subjects, and other reported clinical experience with triamcinolone ...

7. link.springer.com link.springer.com/article/10.1007/s40744-022-00430-3

A Randomized, Open-Label, Single-Dose Study to Assess ... We compared the safety and systemic exposure of TA extended-release (TA-ER) versus TA crystalline suspension (TAcs) in patients with hip osteoarthritis.