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

NCT ID: NCT03282149

Last Updated: 2019-07-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-03-21
• Study Completion Date: 2019-06-15

Brief Summary

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

Detailed Description

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

Subjects for whom replacement knee surgery is recommended will be enrolled in the study. A single injection of a DNA plasmid with a variant Interleukin-10 (IL-10) transgene will be injected into the synovial capsule of the knee.

This is a first in human, dose-range, safety and efficacy study.

Conditions

Osteoarthritis, Knee

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Dose 1

Lowest trial dose of XT-150

Group Type: EXPERIMENTAL

XT-150

Intervention Type: BIOLOGICAL

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

Dose 2

Second, escalating dose of XT-150

Group Type: EXPERIMENTAL

XT-150

Intervention Type: BIOLOGICAL

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

Dose 3

Third, escalating dose of XT-150

Group Type: EXPERIMENTAL

XT-150

Intervention Type: BIOLOGICAL

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

Saline placebo

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

Group Type: PLACEBO_COMPARATOR

XT-150

Intervention Type: BIOLOGICAL

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

Interventions

XT-150

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

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

1. Male or female, between 18 and 90 years of age, inclusive. Women who are not of child-bearing potential in the same age range.

2. 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.

3. Symptomatic disease because of osteoarthritis, defined as one or more of the following Verbal Numerical Rating Scale (VNRS) scores:

1. 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").

2. 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").

4. Stable analgesic regimen during the 4 weeks prior to enrollment.

5. Inadequate pain relief (mean >5 mean on Brief Pain Inventory-Severity Scale) from prior therapies lasting 3 months.

6. In the judgment of the Investigator, acceptable general medical condition

7. Life expectancy >6 months

8. 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.

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 reliably provide pain assessment

12. 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 knee replacement within 4 months; participant agrees not to schedule a knee replacement appointment within 4 months of study treatment

3. History of rheumatoid arthritis of the knee

4. 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])

5. Current treatment with immunosuppressive (systemic corticosteroid therapy [equivalent to >10mg/day prednisone] or other strong immunosuppressant)

6. History of immunosuppressive therapy; high-potency systemic steroids in the last 3 months.

7. Currently receiving systemic chemotherapy or radiation therapy for malignancy

8. 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)

9. 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)

10. Positive serology for human immunodeficiency virus, hepatitis B virus, or hepatitis C virus within 4 weeks of commencing the study

11. Significant neuropsychiatric conditions; dementia, major depression, or altered mental state that in the opinion of the Investigator will interfere with study participation

12. Current treatment with systemic antibiotics or antivirals (EXCEPTION: topical treatments)

13. Current treatment with anticoagulants, other than low-dose aspirin, prescribed for new onset of symptoms in 3 months before screening visit.

14. Known or suspected history of active alcohol or intravenous/oral drug abuse within 1 year before the screening visit

15. Women of child-bearing potential

16. 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.

17. Any condition that, in the opinion of the Principal Investigator, could compromise the safety of the participant, the participant's ability to communicate the study staff, or the quality of the data

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Xalud Therapeutics, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mark Rickman, MD

Role: PRINCIPAL_INVESTIGATOR

University of Adelaide

Locations

CMAX Clinical Research Pty Ltd in collaboration with University of Adelaide

Adelaide, South Australia, Australia

Countries

Australia

Other Identifiers

XT-150-1-0201

Identifier Type: -

Identifier Source: org_study_id