Efficacy and Safety of XT-150 in Osteoarthritis of the Knee

Xalud Therapeutics

Status and phase: Completed; Phase 2

Conditions: Osteoarthritis, Knee

Treatments: Drug: Placebo; Biological: XT-150

Study type: Interventional

Funder types: Industry

Identifiers

NCT04124042

XT-150-2-0204

Details and patient eligibility

About

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.

Full 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.

Enrollment: 289 patients

Sex: All

Ages: 45 to 85 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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289 participants in 6 patient groups, including a placebo group

Stage A: 0.15 mg/mL XT-150, Stage B: 0.15 mg/mL XT-150

Experimental group

Description:

Low dose active in Stage A and Stage B

Treatment:

Biological: XT-150

Stage A: 0.15 mg/mL XT-150, Stage B: 0.45 mg/mL XT-150

Experimental group

Description:

Low dose active in Stage A, high dose active in Stage B

Treatment:

Biological: XT-150

Stage A: 0.45 mg/mL XT-150, Stage B: 0.15 mg/mL XT-150

Experimental group

Description:

High dose active in Stage A, low dose active in Stage B

Treatment:

Biological: XT-150

Stage A: 0.45 mg/mL XT-150, Stage B: 0.45 mg/mL XT-150

Experimental group

Description:

High dose active in Stage A and Stage B

Treatment:

Biological: XT-150

Stage A: Placebo, Stage B: 0.15 mg/mL XT-150

Placebo Comparator group

Description:

Inactive comparator in Stage A, low dose active in Stage B

Treatment:

Biological: XT-150

Drug: Placebo

Stage A: Placebo, Stage B: 0.45 mg/mL XT-150

Placebo Comparator group

Description:

Inactive comparator in Stage A, high dose active in Stage B

Treatment:

Biological: XT-150

Drug: Placebo