Efficacy and Safety of XT-150 in Osteoarthritis of the Knee

A Double-Blind, Placebo-Controlled Assessment of the Tolerability and Efficacy of XT-150 for the Treatment of Moderate to Severe Pain Due to Osteoarthritis of the Knee

This is a Phase 2 safety and efficacy study of XT-150 in adult participants experiencing moderate to severe pain due to osteoarthritis of the knee.

Study Overview

• Status: Completed
• Conditions: Osteoarthritis, Knee
• Intervention / Treatment: Drug: Placebo; Biological: XT-150

Detailed Description

In this Phase 2 study, Baseline (Day 0) confirmation of study eligibility will be completed the day before or day of study drug administration.

Study drug will be administered by intra-articular (IA) injection into the joint space of the index knee (knee selected for treatment).

Up to 270 participants will be randomly enrolled into 1 of 6 treatment sequences (45 participants/ group). Treatment Groups:

1. 0.15 mg/mL XT-150 (1mL), 0.15 mg/mL XT-150 (1mL)
2. 0.15 mg/mL XT-150 (1mL), 0.45 mg/mL XT-150 (1mL)
3. 0.45 mg/mL XT-150 (1mL), 0.15 mg/mL XT-150 (1mL)
4. 0.45 mg/mL XT-150 (1mL), 0.45 mg/mL XT-150 (1mL)
5. Placebo (1mL), 0.15 mg/mL XT-150 (1mL)
6. Placebo (1mL), 0.45 mg/mL XT-150 (1mL)

The study will be conducted in 2 stages, A and B. Participants will be randomized at Day 0 to a treatment regimen, one treatment assignment for Stage A and one treatment assignment for Stage B:

Stage A (Up to Day 180): Participants will receive placebo, 0.15 mg/mL XT-150 or 0.45 mg/mL XT-150 to the index knee at Day 0.

Stage B (Day 180 to Day 360): Participants will have the option to receive a pre-randomized dose (XT-150 0.15 mg/mL or 0.45 mg/mL) to the index knee anytime between Day 180 and Day 330.

Final assessments will be 12 months after the first IA dose.

• Study Type: Interventional
• Enrollment (Actual): 289
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • South Australia
    • Adelaide, South Australia, Australia, 5005
      • University of Adelaide in collaboration with CMAX Clinical Research Pty Ltd
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Alfred Health
• United States
  • California
    • La Mesa, California, United States, 91942
      • eStudySite
    • Napa, California, United States, 94558
      • Neurovations (Napa Pain Institute)
    • Santa Monica, California, United States, 90403
      • Source Healthcare
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27103
      • Carolinas Clinical Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Symptomatic disease due to osteoarthritis, defined as a WOMAC Pain score ≥ 8 (worst possible = 20)
2. Focused Analgesia Selection Test will be used to determine whether patients can report pain with sufficient consistency to enter the clinical trial
3. Males and females between 45 and 85 years of age, inclusive
4. Kellgren-Lawrence grading of 2 or 3 within the last 6 months
5. Stable analgesic regimen during the 4 weeks prior to enrollment
6. In the judgment of the Investigator, acceptable general medical condition
7. Life expectancy >6 months
8. Male and female participants who are heterosexually active and not surgically sterile must agree to use effective contraception, including abstinence, for the duration of the study
9. Have suitable knee joint anatomy for intra-articular injection
10. Willing and able to return for the follow-up (FU) visits
11. Able to read and understand study instructions, and willing and able to comply with all study procedures

Exclusion Criteria:

1. Hypersensitivity, allergy, or significant reaction to any ingredient of the study drug, including double-stranded DNA, mannose, and sucrose
2. Previously received XT-150 injection(s)
3. Scheduled partial or complete knee replacement within 6 months; participant agrees not to schedule a knee replacement during Stage A of the study
4. History of knee arthroplasty on the Index Knee, i.e., selected for study injection(s)
5. History of rheumatoid arthritis or other inflammatory disease
6. History of immunosuppressive therapy; systemic steroids in the last 3 months
7. Received knee injection with hyaluronic acid or stem-cells in the last 6 months
8. Knee injection of glucocorticoid in the last 3 months
9. Current treatment with systemic immunosuppressive (systemic corticosteroid therapy or other strong immunosuppressant)
10. Currently receiving systemic chemotherapy or radiation therapy for malignancy
11. Clinically significant hepatic disease as indicated by clinical laboratory results ≥3 times the upper limit of normal for any liver function test (e.g., aspartate aminotransferase, alanine aminotransferase)
12. Severe anemia (Grade 3; hemoglobin <8.0 g/dL, <4.9 mmol/L, <80 g/L; transfusion indicated), Grade 1 white cell counts (lymphocytes <LLN - 800/mm^3; <LLN - 0.8 x 109 /L, neutrophils <LLN - 1500/mm^3; <LLN - 1.5 x 109 /L), LLN=Lower Limit Normal Range
13. Positive serology for human immunodeficiency virus, hepatitis B virus, or hepatitis C virus
14. Significant neuropsychiatric conditions; dementia, major depression, or altered mental state that in the opinion of the Investigator will interfere with study participation
15. Current treatment with systemic antibiotics or antivirals (EXCEPTION: topical treatments)
16. Current anticoagulant or anti-platelet treatment (e.g., warfarin, heparins, factor X inhibitors, clopidogrel, prasugrel, ticagrelor, or dipyridamole). Low-dose (≤ 325 mg/day) aspirin is permitted
17. Known or suspected history of active alcohol or intravenous/oral drug abuse within 1 year before the screening visit
18. Use of any investigational drug or device within 3 months before enrollment or current participation in a trial that included intervention with a drug or device; or currently participating in an investigational drug or device study
19. Any condition that, in the opinion of the Investigator, could compromise the safety of the participant, the participant's ability to communicate with the study staff, or the quality of the data

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Stage A: 0.15 mg/mL XT-150, Stage B: 0.15 mg/mL XT-150; Low dose active in Stage A and Stage B	Biological: XT-150; plasmid DNA
Experimental: Stage A: 0.15 mg/mL XT-150, Stage B: 0.45 mg/mL XT-150; Low dose active in Stage A, high dose active in Stage B	Biological: XT-150; plasmid DNA
Experimental: Stage A: 0.45 mg/mL XT-150, Stage B: 0.15 mg/mL XT-150; High dose active in Stage A, low dose active in Stage B	Biological: XT-150; plasmid DNA
Experimental: Stage A: 0.45 mg/mL XT-150, Stage B: 0.45 mg/mL XT-150; High dose active in Stage A and Stage B	Biological: XT-150; plasmid DNA
Placebo Comparator: Stage A: Placebo, Stage B: 0.15 mg/mL XT-150; Inactive comparator in Stage A, low dose active in Stage B	Drug: Placebo; Placebo is a sterile phosphate-buffered saline; Biological: XT-150; plasmid DNA
Placebo Comparator: Stage A: Placebo, Stage B: 0.45 mg/mL XT-150; Inactive comparator in Stage A, high dose active in Stage B	Drug: Placebo; Placebo is a sterile phosphate-buffered saline; Biological: XT-150; plasmid DNA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stage A: Number of participants achieving 30% improvement from Baseline in Western Ontario and McMasters Arthritis Index (WOMAC) pain score	WOMAC pain score will be obtained from Knee injury and Osteoarthritis Outcome Score (KOOS) questionnaire which is a validated, commonly used instrument to assess the participant's opinion about their knee and associated problems. Each item is answered on a 5-point Likert scale. The score for pain category ranges from 0 (no pain) to 20 (maximum pain); higher score indicates worse outcomes. Baseline is defined as the Day 0 value.	Up to Day 180
Stage A: Change from Baseline in WOMAC Pain Score at Day 180		At Day 180
Stage A: Number of participants with adverse events (AEs) and serious adverse events (SAEs)		Up to Day 180
Stage B: Number of participants with AEs and SAEs		Up to Day 360

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stage B: Change from Baseline in WOMAC Pain Score at Day 360		At Day 360
Stage A and Stage B: Change from Baseline in WOMAC function score	WOMAC function score will be obtained from KOOS questionnaire which is a is a validated, commonly used instrument to assess the participant's opinion about their knee and associated problems. Each item is answered on a 5-point Likert scale. The function dimension category asks about the degree of difficulty in doing 17 activities. The score ranges from 0 (normal function) to 170 (severely limited function); higher score indicates worse outcomes. Baseline is defined as the Day 0 value.	Up to Day 360
Stage A and Stage B: Change from Baseline in Brief Pain Inventory (BPI) of Interference score	The BPI is a self-administered questionnaire for participants to rate the degree to which their pain interferes with common dimensions of feeling and function. The 7 pain interference items will be rated on 0-10 scale. Total interference score ranges from 0 (does not interfere) to 10 (completely interferes); higher score indicates worse outcomes.	Up to Day 360
Stage A and Stage B: Change from Baseline in Patients Overall Assessment (POA)	The POA is a self-administered questionnaire that records participants' responses to the question "Considering all the ways the OA in your knee affects you, how are you doing today?" on a scale of 1 to 5; 1 being very good (asymptomatic and no limitation of normal activities) to 5, very poor (very severe, intolerable symptoms and inability to carry out normal activities). Higher score indicates worse symptoms.	Up to Day 360
Stage A and B: Number of participants with presence of anti-interleukin (IL)-10 antibody		Up to Day 360

Collaborators and Investigators

• Sponsor: Xalud Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): February 14, 2020
• Primary Completion (Actual): April 26, 2022
• Study Completion (Actual): April 26, 2022

Study Registration Dates

• First Submitted: October 9, 2019
• First Submitted That Met QC Criteria: October 9, 2019
• First Posted (Actual): October 11, 2019

Study Record Updates

• Last Update Posted (Estimate): January 13, 2023
• Last Update Submitted That Met QC Criteria: January 9, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: Inflammation; Gene Therapy; Pain; Interleukin; plasmid DNA
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee
• Other Study ID Numbers: XT-150-2-0204

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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