A Study to Assess the Safety and Efficacy of a Single Dose of UBX0101 in Patients With Osteoarthritis of the Knee

Study Overview
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Brief Summary
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A study to assess efficacy, safety, and tolerability of a single-dose intra-articular administration of UBX0101 in patients with moderate to severe painful knee osteoarthritis (OA).

Detailed Description
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This is a randomized, double-blind, placebo-controlled, single-dose, parallel-group study to assess the efficacy, safety, and tolerability of a single-dose intra-articular (IA) administration of UBX0101 in patients with moderate to severe painful knee osteoarthritis (OA). Approximately 180 patients will be randomized (1:1:1:1) to one of four treatment groups (three dose levels of UBX0101 and Placebo; approximately 45 patients per group), all administered by IA route at Week 0. The four treatment groups will be enrolled concurrently. The primary objective of the study is to evaluate the effect of IA administration of UBX0101 on the change from baseline to Week 12 of pain in the target knee.

Official Title
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A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Single-Dose Study of UBX0101 in Moderate to Severe, Painful Osteoarthritis of the Knee

Conditions
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Osteoarthritis, Knee

Intervention / Treatment
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* Drug: UBX0101
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Patients who are ambulatory with a diagnosis of OA of the knee and who have baseline pain with a mean of ≥ 4 and ≤ 9 on the 11-point (0-10) average daily pain NRS for at least five of seven days during the Screening period. Kellgren-Lawrence grade of 1-4 on a weight-bearing radiograph of target knee. Patients aged ≥ 40 and ≤ 85 years. Patients are permitted but not required to use an oral NSAID, serotonin and norepinephrine reuptake inhibitors (SNRIs), tramadol, or acetaminophen, provided that they have been taking a stable dose and regimen of medication for at least 4 weeks prior to Screening. Key Exclusion Criteria: Patients with any condition, including laboratory or imaging findings and findings in the medical history or in the pre-study assessments, that in the opinion of the Investigator or the Medical Monitor constitutes a risk or contraindication for participation in the study or that could interfere with the study objectives, conduct, or evaluation or prevent the patient from fully participating in all aspects of the study. Patients with a body mass index (BMI) ≥40 kg/m2 or a body habitus that precludes the MRI. Patients with fibromyalgia Systemic autoimmune disease with musculoskeletal involvement or any history of a systemic inflammatory arthritis Patients who have received IA treatment in the target knee with steroids or hyaluronic acid derivatives within the last 16 weeks prior to Screening, or with extended-release corticosteroid (e.g., Zilretta®) within the last 20 weeks Patients who are using a topical NSAID or topical analgesics on the target knee. Patients who have used opioid analgesics (other than tramadol), marijuana or marijuana-derived products (e.g., cannabidiol), and topical capsaicin on the target knee within 8 weeks prior to Screening Patients with a history of traumatic knee injury to the target knee, including, but not limited to, patients with meniscal root tear, within 2 years of study entry. Patients who have undergone diagnostic arthroscopy to the target knee in the previous 6 months. Patients who have undergone arthroscopic surgery (including microfracture and meniscectomy) on the target knee in the last 2 years prior to the Screening visit or are anticipated to have arthroscopic surgery on either knee at any time during the study period. Patients with a history of previous total or partial knee arthroplasty. Patients with an effusion at the Screening visit, which, in the opinion of the Investigator following examination and discussions with the patient, requires drainage for symptom relief. Patients who have had regenerative joint procedures on any joint, including, but not limited to, platelet-rich plasma injections, stem cell transplantation, autologous chondrocyte transplantation, or mosaicplasty. Patients with secondary arthritis that involves the target knee or would confound assessments of knee OA

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Other: Placebo<br>* Placebo intra-articular injection<br>|
| Experimental: UBX0101 0.5 mg<br> | Drug: UBX0101<br>* Investigational drug intra-articular injection<br>|
| Experimental: UBX0101 2.0 mg<br> | Drug: UBX0101<br>* Investigational drug intra-articular injection<br>|
| Experimental: UBX0101 4.0 mg<br> | Drug: UBX0101<br>* Investigational drug intra-articular injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 12 of the Western Ontario and McMaster Universities Osteoarthritis Index Pain Subscale (WOMAC-A) Score in Patients Receiving a Single Dose of UBX0101 Versus Those Receiving Placebo | WOMAC-A is assessed by a Likert scale on a range from 0 (none) to 4 (extreme), with higher scores indicating higher levels of pain | Baseline to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 12 of the Western Ontario and McMaster Universities Osteoarthritis Index Function Subscale (WOMAC-C) Score in Patients Receiving a Single Dose of UBX0101 Versus Those Receiving Placebo | WOMAC-C is assessed by a Likert scale on a range from 0 (none) to 4 (extreme), with higher scores indicating higher levels of physical disability | Baseline to Week 12 | 
| Change From Baseline to Week 12 of the Weekly Mean of the Average Daily Pain (ADP) Intensity Scores on the 11-point Numeric Rating Scale (NRS) in Patients Receiving a Single Dose of UBX0101 Versus Those Receiving Placebo | ADP is assessed by NRS on a range from 0 (no pain) to 10 (worst pain imaginable), with higher scores indicating higher levels of pain | Baseline to Week 12 | 
| Change From Baseline (Over the Entire 24-week Period, Including Both the Primary Study Period and the 12-week Follow-up Period) to Week 24 for the WOMAC-A, NRS, and WOMAC-C Scores in Patients Receiving a Dose of UBX0101 Versus Those Receiving Placebo | WOMAC-A is assessed by a Likert scale on a range from 0 (none) to 4 (extreme), with higher scores indicating higher levels of pain WOMAC-C is assessed by a Likert scale on a range from 0 (none) to 4 (extreme), with higher scores indicating higher levels of physical disability. Average Daily Pain (ADP) is assessed by Numerical Rating Score (NRS) on a range from 0 (no pain) to 10 (worst pain imaginable), with higher scores indicating higher levels of pain. | Baseline to Week 24 | 
| Incidence of Treatment Emergent Adverse Events (TEAEs) |  | Baseline to Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Osteoarthritis, Painful Osteoarthritis, Osteoarthritis, Knee, Senescence