A Study of Single and Repeat Dose Administration of UBX0101 in Patients With Osteoarthritis of the Knee

A Double-Blind, Randomized, Placebo-Controlled Study of Single and Repeat Dose Administration of UBX0101 in Moderate to Severe, Painful Osteoarthritis of the Knee

A study to assess safety, tolerability and clinical effects of single and repeat dose intra-articular administration of UBX0101 in patients with moderate to severe painful knee osteoarthritis (OA).

Study Overview

• Status: Completed
• Conditions: Knee Osteoarthritis
• Intervention / Treatment: Drug: UBX0101; Other: Placebo

Detailed Description

This is a randomized, double-blind, placebo-controlled study conducted as two parallel cohorts to assess the safety, tolerability, and clinical effects of single dose (SD) and repeat dose (RD) intra-articular (IA) administration of UBX0101 in patients with symptomatic knee osteoarthritis (OA).

Approximately 36 patients will be randomly assigned to either Cohort 1 (SD) or Cohort 2 (RD) (18 patients per treatment cohort) and further randomized in a 2:1 ratio to UBX0101 and placebo in each cohort.

The primary objective of the study is to evaluate the safety and tolerability of SD and RD IA administration of UBX0101 over 24 weeks.

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • The Villages, Florida, United States, 32159
      • Premier Medical Associates
  • Georgia
    • Marietta, Georgia, United States, 30060
      • Drug Studies America
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • Sundance Clinical Research, LLC
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • Hassman Research Institute
  • New York
    • Rochester, New York, United States, 14609
      • Rochester Clinical Research, Inc.
  • South Carolina
    • North Charleston, South Carolina, United States, 29406
      • Arcis Healthcare LLC dba Lowcountry Orthopaedics and Sports Medicine
  • Texas
    • Bellaire, Texas, United States, 77401
      • First Surgical Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Patients who are ambulatory with a diagnosis of OA of the knee and who have moderate to severe knee pain as measured on the 11-point (0-10) average daily pain NRS.
• 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.
• 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 in the target knee.
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: UBX0101 single dose (SD); Cohort 1 (n=18): UBX0101 8.0 mg or placebo IA at Week 0 Patients will be randomized in a 2:1 ratio to UBX0101 and placebo	Drug: UBX0101; Investigational drug intra-articular (IA) injection; Other: Placebo; Placebo intra-articular (IA) injection
Experimental: UBX0101 repeat dose (RD); Cohort 2 (n=18): UBX0101 4.0 mg or placebo IA at Weeks 0 and 4 Patients will be randomized in a 2:1 ratio to UBX0101 and placebo	Drug: UBX0101; Investigational drug intra-articular (IA) injection; Other: Placebo; Placebo intra-articular (IA) injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety and tolerability of a single and repeat dose intra-articular administration of UBX0101 evaluated by the incidence of serious and non-serious adverse events	Baseline to Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma UBX0101 drug concentrations following IA administration		1, 2, and 4 hours post-dose for both cohorts on Day 1 and at 1, 2, and 4 hours post-dose at Week 4 for Cohort 2 only
Change from baseline to Week 12 of the Western Ontario and McMaster Universities Osteoarthritis Index pain subscale (WOMAC-A) score in patients receiving 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
Change from baseline to Week 24 of the WOMAC-A score over time in patients receiving 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 24
Change from baseline to Week 12 of the Western Ontario and McMaster Universities Osteoarthritis Index function subscale (WOMAC-C) score in patients receiving 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 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

Collaborators and Investigators

• Sponsor: Unity Biotechnology, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): January 23, 2020
• Primary Completion (Actual): September 18, 2020
• Study Completion (Actual): September 18, 2020

Study Registration Dates

• First Submitted: January 9, 2020
• First Submitted That Met QC Criteria: January 10, 2020
• First Posted (Actual): January 18, 2020

Study Record Updates

• Last Update Posted (Actual): October 19, 2020
• Last Update Submitted That Met QC Criteria: October 14, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: Osteoarthritis; Osteoarthritis, Knee; Senescence; Painful Osteoarthritis
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee
• Other Study ID Numbers: UBX0101-MUS-102

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No