Clinical trial NCT04124042: Efficacy and Safety of XT-150 in Osteoarthritis of the Knee
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Osteoarthritis, Knee
Keywords: Inflammation
Pain
Interleukin
Gene Therapy
plasmid DNA
Lead sponsor: Xalud Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2019-10-11
Enrollment: 289
Sex: ALL
Minimum age (years): 45
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Stage A: Number of Participants Achieving 30% Improvement From Baseline in Western Ontario and McMasters Arthritis Index (WOMAC) Pain Score
timeFrame: Day 180
measure: Stage A: Change From Baseline in WOMAC Pain Score at Day 180
timeFrame: Day 180
measure: Stage A: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Prior to second dose (Up to Day 180-Day 330)
measure: Stage B: Number of Participants With AEs and SAEs
timeFrame: Post Second Dose (Day 180-Day 330 through Day 360)
Secondary outcomes:
measure: Stage B: Change From Baseline in WOMAC Pain Score at Day 360
timeFrame: Day 360
measure: Stage B: Change From Baseline in WOMAC Function Score
timeFrame: At Day 360
measure: Stage A: Change From Baseline in Brief Pain Inventory (BPI) of Interference Score
timeFrame: Day 180
measure: Stage A: Change From Baseline in Patients Overall Assessment (POA)
timeFrame: Day 180
measure: Stage A and B: Number of Participants With Presence of Anti-interleukin (IL)-10 Antibody
timeFrame: Up to Day 360
Other outcomes:
Locations:
city: La Mesa
country: United States
facility: eStudySite
state: California
city: Napa
country: United States
facility: Neurovations (Napa Pain Institute)
state: California
city: Santa Monica
country: United States
facility: Source Healthcare
state: California
city: Winston-Salem
country: United States
facility: Carolinas Clinical Research Institute
state: North Carolina
city: Adelaide
country: Australia
facility: University of Adelaide in collaboration with CMAX Clinical Research Pty Ltd
state: South Australia
city: Melbourne
country: Australia
facility: Alfred Health
state: Victoria
Study officials:
References: