Safety, Tolerability, and Efficacy of XT-150 for the Treatment of Osteoarthritic Pain

NCT03477487 | Completed Phase 1 FDA Drug

• 1 other identifier: XT-150-1-0202
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

Evaluation of Safety, Tolerability, and Efficacy of XT-150, a plasmid DNA with a variant of human IL-10 transgene. XT-150 will be a single injection into the knee synovial capsule for the Treatment of Osteoarthritic Pain.

Conditions

Osteoarthritis, Knee

Keywords

inflammation; Cytokines; Interleukin-10; Gene therapy

Outcome Measures

Primary Outcomes (1)

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  Clinical, laboratory measures of safety by CTCAE v4.0

  6 months

Secondary Outcomes (4)

• Visual Analog Scale of Pain Intensity

  6 months

• Knee Injury and Osteoarthritis Outcomes Scale

  6 months

• WOMAC

  6 Months

• Brief Pain Inventory

  6 months

Study Arms (4)

Lowest dose

EXPERIMENTAL

The lowest dose of XT-150 in the escalation schedule

Biological: XT-150

Second dose

EXPERIMENTAL

The 2nd dose of XT-150 in the escalation sequence

Biological: XT-150

Third dose

EXPERIMENTAL

The 3rd dose of XT-150 in the escalation sequence

Biological: XT-150

Highest dose

EXPERIMENTAL

The highest dose of XT-150 in the escalation sequence

Biological: XT-150

Interventions

XT-150 BIOLOGICAL

Human IL-10 variant transgene in a plasmid DNA vector

Highest dose; Lowest dose; Second dose; Third dose

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, between 18 and 90 years of age, inclusive
• Sufficiently severe OA of the knee to meet accepted criteria for knee arthroplasty
• Free of intra-articular infection, or infection at the injection site.
• Symptomatic disease because of osteoarthritis, defined as one or more of the following Visual Analog Scale of Pain Intensity (VASPI) scores:
• a worst pain of at least 70 at any time during the preceding week (based on scale of 0 to 100, with 100 representing "pain as bad as you can imagine").
• a worst stiffness of at least 70 at any time during the preceding week (based on a scale of 0 to 100, with 100 representing "stiffness as bad as you can imagine").
• Stable analgesic regimen during the 4 weeks prior to enrollment.
• Inadequate pain relief (minimum ≥5 mean on the Brief Pain Inventory-Severity Scale) lasting ≥3 months.
• In the judgment of the Investigator, acceptable general medical condition
• Life expectancy \>6 months
• Female subjects of child-bearing potential, and those \<1 year post-menopausal, must be practicing effective methods of birth control such as hormonal methods (e.g., combined oral, implantable, injectable, or transdermal contraceptives), double barrier methods (e.g., condoms, sponge, diaphragm) or total abstinence from heterosexual intercourse for a minimum of 1 month before study drug administration and agree to continue prevention methods for 3 months after participation in the study is completed.
• Male subjects who are heterosexually active and not surgically sterile must agree to use effective contraception, including abstinence, for the duration of the study and for 3 months after the study is completed.
• Have suitable knee joint anatomy for intra-articular injection
• Willing and able to return for the follow-up (FU) visits
• Able to reliably provide pain assessment

You may not qualify if:

• \. Hypersensitivity, allergy, or significant reaction to any ingredient of the study drug, including double-stranded DNA, mannose, and sucrose
• Subject plans knee arthroplasty within 4 months, irrespective of the outcome of the trial or other conservative therapies
• High peri-procedural risks which in the judgment of the investigator preclude a safe knee injection procedure (e.g., poorly controlled diabetes, cardiac inadequacy such as NYHA class \> II, G4 glomerular filtration rate \[eGFR \< 30 mL/min by Cockcroft-Gault\])
• Current treatment with immunosuppressives (steroid therapy equivalent to \>10mg/day prednisone); or other strong immunosuppressant
• History of systemic immunosuppressive therapy; steroids (equivalent to \>10mg/day prednisone) in the last 3 months
• Currently receiving systemic chemotherapy or radiation therapy for malignancy
• 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)
• Severe anemia (Grade 3; hemoglobin \<8.0 g/dL, \<4.9 mmol/L, \<80 g/L; transfusion indicated), uncontrolled coagulopathy (Grade 1, prolonged activated partial prothrombin time (aPTT) \> upper limit of normal (ULN) to 1.5xULN), or bleeding diathesis, Grade 1 white cell counts (lymphocytes \<LLN - 800/mm3; \<LLN - 0.8 x 10e9 /L, neutrophils \<LLN - 1500/mm3; \<LLN - 1.5 x 10e9 /L)
• Positive serology for human immunodeficiency virus, hepatitis B virus, or hepatitis C virus within 4 weeks of commencing the study
• Significant neuropsychiatric conditions; dementia, major depression, or altered mental state that in the opinion of the Investigator will interfere with study participation
• Current treatment with systemic antibiotics or antivirals (EXCEPTION: topical treatments)
• Current treatment with anticoagulants, other than low-dose aspirin, prescribed for new onset of symptoms in 3 months before screening visit.
• Known or suspected history of active alcohol or intravenous/oral drug abuse within 1 year before the screening visit
• Women who are pregnant or nursing
• 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.

Sponsors & Collaborators

• Xalud Therapeutics, Inc.: lead

Study Sites (1)

Neurovations (Napa Pain Institute)

Napa, California, 94558, United States

Location

MeSH Terms

Conditions

Osteoarthritis, Knee; Inflammation

Condition Hierarchy (Ancestors)

Osteoarthritis; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Stephen Collins, MD, PhD

  Xalud Therapeutics, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Ascending dose-ranging study

Study Record Dates

• First Submitted: March 13, 2018
• First Posted: March 26, 2018
• Study Start: June 8, 2018
• Primary Completion: July 19, 2019
• Study Completion: September 30, 2019
• Last Updated: November 8, 2019

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)