Preliminary Safety and Efficacy of XT-150 in Facet Joint Osteoarthritis

• ClinicalTrials.gov Identifier: NCT04841512
• Recruitment Status: Recruiting
• First Posted: April 12, 2021
• Last Update Posted: October 25, 2021
• Sponsor: Xalud Therapeutics, Inc.
• Information provided by (Responsible Party): Xalud Therapeutics, Inc.

Study Description

Brief Summary:

Preliminary safety and efficacy of XT-150 in the synovial capsule of osteoarthritic facet joints in the vertebra of the spine.

Condition or disease	Intervention/treatment	Phase
Osteoarthritis, Spine	Biological: XT-150	Phase 1; Phase 2

Detailed Description:

This is a Phase 1, safety and efficacy study of XT-150 in adult participants experiencing back pain due to inflammation of the facet joint osteoarthritis (FJOA) and who are eligible for intra-synovial glucocorticoid injection, or radiofrequency ablation of medial branches of the primary dorsal ramus of the exiting nerve root, which innervates the adjacent facet joints.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Masking Description: Unblinded pharmacy, blinded clinical staff for administration and assessments
• Primary Purpose: Treatment
• Official Title: A Placebo-controlled, Double-blind Evaluation of Safety, Tolerability, and Efficacy of XT-150 for the Treatment of Facet Joint Osteoarthritis Pain
• Estimated Study Start Date: January 2022
• Estimated Primary Completion Date: March 2023
• Estimated Study Completion Date: May 2023

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Placebo; Sterile phosphate-buffered saline for injection Single 1mL injection into the facet joint	Biological: XT-150; non-viral Plasmid DNA encoding an IL-10 variant transgene
Experimental: XT-150 Dose #1; Lower dose of XT-150 sterile solution for injection Single 1 mL injection into the facet joint	Biological: XT-150; non-viral Plasmid DNA encoding an IL-10 variant transgene
Experimental: XT-150 Dose #2; Higher dose of XT-150 sterile solution for injection Single 1 mL injection into the facet joint	Biological: XT-150; non-viral Plasmid DNA encoding an IL-10 variant transgene

Outcome Measures

Primary Outcome Measures :

1. Visual analog scale (VAS) [ Time Frame: 6 months ]
   0 - 100, 100 worst possible pain

Secondary Outcome Measures :

1. Oswestry Disability Index [ Time Frame: 6 months ]
   10 dimensions, 0 - 5 score in each, with 5 as worst score in a dimension

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 90 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Male or female, between 18 and 90 years of age, inclusive.
2. Sufficiently severe facet arthropathy (OA) of lumbar facets as determined by imaging, eg. CT or MRI, to establish an underlying basis of disease, as determined by usual bony and ligamentous signs of OA.
3. Complaint of nociceptive, mechanical pain of lumbar spine, in particular pain localized to paramedian axis as opposed to midline or radicular. Radicular pain as a secondary finding may be allowed if it is addition to mechanical pain and can be clinically distinguished by subject
4. Low Back Pain (LBP) worsened by activity or motion of region
5. Have had a positive diagnostic facet pain block with lignocaine; admittance if subject gains 50% relief of pain within 30 minutes of test injection
6. Be free of local or intra-articular infection, tumor or other causes of localized LBP, for example Including spondylolysis/pars defect, and adjacent vertebral body compression fracture based on MRI evaluation.
7. Symptomatic disease because of osteoarthritis, established by imaging of facet joint and defined as a worst pain of at least 40 at any time during the preceding week (based on scale of 0 to 100, with 100 representing "pain as bad as you can imagine") using Visual Analog Scale (VAS).
8. Stable analgesic regimen during the 4 weeks prior to enrollment.
9. Inadequate pain relief (minimum ≥50 mean on VAS with prior therapies lasting ≥3 months.
10. In the judgment of the Investigator, acceptable general medical condition
11. Male and female participants who are heterosexually active and not surgically sterile or post-menopausal must agree to use effective contraception, including abstinence, for the duration of the study and for 3 months after the study is completed
12. Have suitable facet joint anatomy for intra-articular injection
13. Willing and able to return for the follow-up (FU) visits
14. Able to reliably provide pain assessment (FAST test score R2≥0.7)
15. 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. Scheduled surgical procedure or nerve ablation to joint within the next 6 months; participant agrees not to schedule a surgical procedure, nerve ablation, or added facet injection within 6 months of study treatment
3. High peri-operative risks which in the judgment of the investigator preclude a safe facet joint injection procedure (e.g. extreme obesity putting injection accuracy at risk, etc.)
4. Current treatment with immunosuppressive (systemic corticosteroid therapy [equivalent to >10mg/day prednisone] or other strong immunosuppressant)
5. History of immunosuppressive therapy; high-potency systemic steroids in the last 3 months.
6. Currently receiving systemic chemotherapy or radiation therapy for malignancy
7. 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, lactate dehydrogenase)
8. 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/mm3; <LLN - 0.8 x 109 /L, neutrophils <LLN - 1500/mm3; <LLN - 1.5 x 109 /L)
9. Positive serology with reflex for human immunodeficiency virus, hepatitis B virus, or hepatitis C virus within 4 weeks of commencing the study
10. Significant neuropsychiatric conditions; dementia, major depression, or altered mental state that in the opinion of the Investigator will interfere with study participation
11. Current treatment with systemic antibiotics or antivirals (EXCEPTION: topical treatments)
12. Current treatment with anticoagulants, other than low-dose aspirin
13. Known or suspected history of active alcohol or intravenous/oral drug abuse within 1 year before the screening visit
14. Use of any investigational drug or device within 1 month 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.
15. Any condition that, in the opinion of the Principal Investigator, could compromise the safety of the participant, the participant's ability to communicate with the study staff, or the quality of the data

Contacts and Locations

Contacts

Contact: Flavia Cicuttini, MD; +61 3 9903 0158; flavia.cicuttini@monash.edu

Locations

Australia, Victoria

Alfred Health; Recruiting

Melbourne, Victoria, Australia, 3004

Contact: Flavia Cicuttini, MD +61 3 9903 0158 flavia.cicuttini@monash.edu

Contact: Anita Wluka, PhD, FRACP, MBBS T: +61 3 9903 0994 anita.wluka@monash.edu

Principal Investigator: Flavia Cicuttini, MD

Sponsors and Collaborators

Xalud Therapeutics, Inc.

More Information

• Responsible Party: Xalud Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT04841512
• Other Study ID Numbers: XT-150-1-0301
• First Posted: April 12, 2021
• Last Update Posted: October 25, 2021
• Last Verified: October 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: Not applicable. All patient records are de-identified

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by Xalud Therapeutics, Inc.:

gene therapy; non-viral plasmid; osteoarthritis

Additional relevant MeSH terms:

Osteoarthritis; Osteoarthritis, Spine; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Spondylarthritis; Spondylitis; Spinal Diseases; Bone Diseases