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

NCT03282149 | Completed Phase 1 FDA Drug

• 1 other identifier: XT-150-1-0201
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Preliminary Evaluation of Safety, Tolerability, and Efficacy of XT-150 for the Treatment of Osteoarthritic Pain - Dose escalation

Conditions

Osteoarthritis, Knee

Keywords

inflammation; cytokine; anti-inflammatory; pain

Outcome Measures

Primary Outcomes (1)

• Incidence of Treatment-Emergent Adverse Events [Safety]

  Clinical Pathology, Adverse Events

  180 days post treatment

Secondary Outcomes (1)

• Verbal Numerical Rating Scale

  180 days post treatment

Study Arms (4)

Dose 1

EXPERIMENTAL

Lowest trial dose of XT-150

Biological: XT-150

Dose 2

EXPERIMENTAL

Second, escalating dose of XT-150

Biological: XT-150

Dose 3

EXPERIMENTAL

Third, escalating dose of XT-150

Biological: XT-150

Saline placebo

PLACEBO COMPARATOR

2 of 8 participants in each cohort will randomly be assigned to placebo

Biological: XT-150

Interventions

XT-150 BIOLOGICAL

IL-10 transgene DNA plasmid injected into the knee synovial capsule

Dose 1; Dose 2; Dose 3; Saline placebo

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. Women who are not of child-bearing potential in the same age range.
• Sufficiently severe OA of knee to require/have recommended knee replacement surgery or be unsuitable for knee replacement surgery or be unsuitable for knee replacement surgery based on co-morbidities or orthopedic considerations; be free of local or intra-articular infection.
• Symptomatic disease because of osteoarthritis, defined as one or more of the following Verbal Numerical Rating Scale (VNRS) scores:
• a worst pain of at least 7 at any time during the preceding week (based on scale of 0 to 10, with 10 representing "pain as bad as you can imagine").
• a worst stiffness of at least 7 at any time during the preceding week (based on a scale of 0 to 10, with 10 representing "stiffness as bad as you can imagine").
• Stable analgesic regimen during the 4 weeks prior to enrollment.
• Inadequate pain relief (mean \>5 mean on Brief Pain Inventory-Severity Scale) from prior therapies lasting 3 months.
• In the judgment of the Investigator, acceptable general medical condition
• Life expectancy \>6 months
• Male participants 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
• Able to read and understand study instructions, and willing and able to comply with all study procedures

You may not qualify if:

• Hypersensitivity, allergy, or significant reaction to any ingredient of the study drug, including double-stranded DNA, mannose, and sucrose
• Scheduled knee replacement within 4 months; participant agrees not to schedule a knee replacement appointment within 4 months of study treatment
• History of rheumatoid arthritis of the knee
• High peri-operative 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 immunosuppressive (systemic corticosteroid therapy \[equivalent to \>10mg/day prednisone\] or other strong immunosuppressant)
• History of immunosuppressive therapy; high-potency systemic steroids 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 of child-bearing potential

Sponsors & Collaborators

• Xalud Therapeutics, Inc.: lead

Study Sites (1)

CMAX Clinical Research Pty Ltd in collaboration with University of Adelaide

Adelaide, South Australia, 5005, Australia

Location

MeSH Terms

Conditions

Osteoarthritis, Knee; Inflammation; Pain

Condition Hierarchy (Ancestors)

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

Study Officials

• Mark Rickman, MD

  University of Adelaide

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Unblinded pharmacy provides injection preparation for blinded administration
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Inflammation and pain due to osteoarthritis in the knee

Study Record Dates

• First Submitted: September 11, 2017
• First Posted: September 13, 2017
• Study Start: March 21, 2018
• Primary Completion: March 31, 2019
• Study Completion: June 15, 2019
• Last Updated: July 5, 2019

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)