A Safety and Tolerability Study of UBX0101 in Patients With Osteoarthritis of the Knee

• ClinicalTrials.gov Identifier: NCT03513016
• Recruitment Status: Completed
• First Posted: May 1, 2018
• Last Update Posted: April 20, 2020
• Sponsor: Unity Biotechnology, Inc.
• Information provided by (Responsible Party): Unity Biotechnology, Inc.

Study Description

Brief Summary:

A study to evaluate safety, tolerability, and pharmacokinetics of a single intra-articular injection of UBX0101 in patients diagnosed with painful osteoarthritis of the knee.

Condition or disease	Intervention/treatment	Phase
Osteoarthritis, Knee	Drug: UBX0101; Other: Placebo	Phase 1

Detailed Description:

This study is a phase 1, randomized, double-blind, placebo-controlled single ascending dose study that will evaluate safety, tolerability, and pharmacokinetics of UBX0101 in patients diagnosed with painful femoro-tibial osteoarthritis. The study consists of 2 parts: Part A is a single ascending dose study, whereas Part B is a single-dose study at a dose that has been determined to be safe and tolerable in Part A of the study.

In Part A, subjects will be randomly allocated to receive UBX0101 or placebo in 3:1 randomization by dose level (cohort), whereas in Part B subjects will be randomly allocated to receive UBX0101 or placebo in a 2:1 randomization.

The primary objective is to establish the safety and tolerability of UBX0101 given as a single intra-articular injection into the femoro-tibial joint of patients with osteoarthritis.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 78 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 1, Double-Blind, Randomized, Placebo Controlled, Single Ascending Dose Study to Assess the Safety and Tolerability of UBX0101 in Moderate to Severe, Painful Osteoarthritis of the Knee
• Actual Study Start Date: May 16, 2018
• Actual Primary Completion Date: March 29, 2019
• Actual Study Completion Date: April 12, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: Part A: UBX0101; Part A: UBX0101, single intra-articular injection, ascending dose	Drug: UBX0101; Investigational drug intra-articular injection
Placebo Comparator: Part A: Placebo; Part A: Placebo, single intra-articular injection, ascending dose	Other: Placebo; Diluent intra-articular injection
Experimental: Part B: UBX0101; Part B: UBX0101, single intra-articular injection, fixed dose	Drug: UBX0101; Investigational drug intra-articular injection
Placebo Comparator: Part B: Placebo; Part B: Placebo, single intra-articular injection, fixed dose	Other: Placebo; Diluent intra-articular injection

Outcome Measures

Primary Outcome Measures :

1. Safety and tolerability of a single intra articular injection of UBX0101 evaluated by the incidence of serious and non-serious adverse events [ Time Frame: 12 weeks ]

Secondary Outcome Measures :

1. Part A: Plasma concentration of UBX0101 over 24 hrs following a single intra-articular injection [ Time Frame: 24 hrs ]
2. Part A: The change from baseline to Week 12 of the weekly mean of the average daily pain intensity score as obtained using the 11-point numerical rating scale [0-10] where 0 represents no pain and 10 represents worst pain imaginable [ Time Frame: Baseline to Week 12 ]
3. Part A: The change from baseline to Week 12 for the Western Ontario and McMaster Universities (WOMAC) index total score and the pain and function subscales using the 5-point Likert scale [ Time Frame: Baseline to Week 12 ]
4. Part B: The change from baseline to Week 4 of selected senescence-associated secretory phenotype factors in plasma samples and in synovial fluid aspirates in patients receiving a single intra-articular injection of UBX0101 versus those receiving placebo. [ Time Frame: Baseline to Week 4 ]
5. Part B: The change from baseline to Week 4 for the Western Ontario and McMaster Universities (WOMAC) index pain subscale using as derived from Knee injury and Osteoarthritis Outcome Score (KOOS). [ Time Frame: Baseline to Week 4 ]
6. Part B: Plasma concentration of UBX0101 following a single intra-articular injection [ Time Frame: 24 hrs ]

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• Patients who have the capacity to give informed consent and who are willing to comply with all study related procedures and assessments. Patients who do not have the legal capacity or medical competency to give written informed consent are not eligible for this study; consent via legally authorized representative will not be accepted
• Patients must be ≥ 40 and ≤ 85 years of age
• Patients using non-steroidal anti-inflammatory agent must be on a consistent regimen, dose, and medication for at least 8 weeks prior to enrollment
• Part A only: Ambulatory persons with osteoarthritis (OA) of the knee and baseline pain with a mean of ≥ 4 and ≤ 9 points on the 24-hour mean pain score (on the 11-point Numeric Rating Scale) for at least five of the seven days during the screening period.
• Part B only: Ambulatory persons with painful osteoarthritis (OA) of the knee for at least six months.
• Part B only: Patients with OA must have Kellgren-Lawrence scores 1 through 4 in the target knee
• Part B only: Patients must have a baseline pain ≥6 on the WOMAC Index pain subscale as derived from the KOOS.

Exclusion Criteria:

• Any condition, including laboratory findings and findings in the medical history or in the pre-study assessments, that in the opinion of the Investigator 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 clinically significant co-existing conditions of the cardiovascular, renal, gastrointestinal, respiratory, nervous, metabolic, or hematologic/ immune systems
• Patients with a history of diabetes mellitus according to the American Diabetes Association criteria or patients previously diagnosed by a qualified physician as having diabetes (American Diabetes Association Standards of Medical Care in Diabetes 2016)
• Patients with a history of cardiac rhythm disturbances, abnormal ECG intervals, or use of medications known to impact ECG intervals
• Patients who have undergone diagnostic arthroscopy of the Target Knee in the previous six months
• Patients who have undergone arthroscopic surgery in the last two years prior to the screening visit (including microfracture and menisectomy) on the Target Knee.
• Patients anticipated to have arthroscopic surgery on either knee at any time during the study period
• History of previous total or partial knee arthroplasty in either knee
• Part A only: 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 received intra-articular treatment with steroids or hyaluronic acid derivatives within the last 16 weeks prior to screening
• Patients who use, or have used in the 8 weeks prior to screening, opioid analgesics (with exception of mild opioid analgesics)
• Patients who have had regenerative joint procedures on any joint including, but not limited to, platelet-rich plasma injections, mesenchymal stem cell transplantation, autologous chondrocyte transplantation, or mosaicplasty
• Current or history of other joint diseases such as joint dysplasia, crystal-induced arthropathy (such as gout, or calcium pyrophosphate deposition disease evidenced by clinical and/or radiographic means), aseptic osteonecrosis, acromegaly, Paget's disease, Ehlers-Danlos Syndrome, Gaucher's disease, Stickler's syndrome, joint infection, hemophilia, hemochromatosis, or neuropathic arthropathy of any cause
• Any active known or suspected systemic autoimmune disease (except for vitiligo, residual auto-immune hypothyroidism only requiring hormone replacement, psoriasis not requiring systemic treatment for two years, conditions not expected to recur in the absence of an external trigger) or any history of a systemic inflammatory arthritis such as psoriatic, rheumatoid, ankylosing spondylitis or reactive arthritis
• Patients diagnosed presently and symptomatic with fibromyalgia based on American College of Radiology (ACR) Criteria
• Patients with a BMI ≥ 40 kg/m2, or whose size exceed the limits of the of the MRI equipment (coil and gantry)

Contacts and Locations

Locations

United States, California

TriWest Research Associates

El Cajon, California, United States, 92020

BioSolutions Clinical Research Center

La Mesa, California, United States, 91942

United States, Florida

Well Pharma Medical Research

Miami, Florida, United States, 33132

United States, Missouri

Center for Pharmaceutical Research

Kansas City, Missouri, United States, 64114

United States, Nevada

Clinical Research Consortium

Las Vegas, Nevada, United States, 89119

United States, Pennsylvania

Altoona Center for Clinical Research

Duncansville, Pennsylvania, United States, 16635

United States, Texas

Metroplex Clinical Research Center

Dallas, Texas, United States, 75231

Sponsors and Collaborators

Unity Biotechnology, Inc.

Investigators

• Study Chair: Jamie Dananberg, MD; UNITY Biotechnology

More Information

• Responsible Party: Unity Biotechnology, Inc.
• ClinicalTrials.gov Identifier: NCT03513016
• Other Study ID Numbers: UBX0101-OAR-101
• First Posted: May 1, 2018
• Last Update Posted: April 20, 2020
• Last Verified: April 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Unity Biotechnology, Inc.:

Osteoarthritis; Painful Osteoarthritis; Osteoarthritis, Knee; Senescence

Additional relevant MeSH terms:

Osteoarthritis; Osteoarthritis, Knee; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases