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

Phase 2

Completed

• Conditions: Osteoarthritis, Knee
• Interventions: Biological: XT-150; Drug: Placebo

• Registration Number: NCT04124042
• Lead Sponsor: Xalud Therapeutics, Inc.

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.

Study Timeline

• Study First Submitted: 2019-10-09
• Study First Submitted QC: 2019-10-09
• Study First Posted: 2019-10-11
• Study Start: 2020-02-14
• Primary Completion: 2022-04-26
• Study Completion: 2022-04-26
• Disposition First Submitted: 2022-11-24
• Results First Submitted: 2024-11-20
• Status Verified: 2025-01
• Results First Submitted QC: 2025-03-07
• Last Update Submitted: 2025-03-07
• Results First Posted: 2025-03-27
• Disposition First Posted: 2025-03-27
• Last Update Posted: 2025-03-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 289

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Stage A: 0.15 mg/mL XT-150, Stage B: 0.15 mg/mL XT-150	XT-150	Low dose active in Stage A and Stage B
Stage A: Placebo, Stage B: 0.15 mg/mL XT-150	Placebo	Inactive comparator in Stage A, low dose active in Stage B
Stage A: Placebo, Stage B: 0.45 mg/mL XT-150	XT-150	Inactive comparator in Stage A, high dose active in Stage B
Stage A: Placebo, Stage B: 0.45 mg/mL XT-150	Placebo	Inactive comparator in Stage A, high dose active in Stage B
Stage A: 0.45 mg/mL XT-150, Stage B: 0.45 mg/mL XT-150	XT-150	High dose active in Stage A and Stage B
Stage A: 0.15 mg/mL XT-150, Stage B: 0.45 mg/mL XT-150	XT-150	Low dose active in Stage A, high dose active in Stage B
Stage A: 0.45 mg/mL XT-150, Stage B: 0.15 mg/mL XT-150	XT-150	High dose active in Stage A, low dose active in Stage B
Stage A: Placebo, Stage B: 0.15 mg/mL XT-150	XT-150	Inactive comparator in Stage A, low dose active in Stage B

Primary Outcome Measures

Name	Time	Method
Stage A: Number of Participants Achieving 30% Improvement From Baseline in Western Ontario and McMasters Arthritis Index (WOMAC) Pain Score	Day 180	The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score will be obtained from the Knee injury and Osteoarthritis Outcome Score (KOOS) questionnaire which is a validated, commonly used instrument to assess the participant's opinion about their knee and associated problems. Each item is answered on a 5-point Likert scale. The score for pain category ranges from 0 (no pain) to 20 (maximum pain); higher score indicates worse outcomes. Baseline is defined as the Day 0 value.
Stage A: Change From Baseline in WOMAC Pain Score at Day 180	Day 180	The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score will be obtained from the Knee injury and Osteoarthritis Outcome Score (KOOS) questionnaire which is a validated, commonly used instrument to assess the participant's opinion about their knee and associated problems. Each item is answered on a 5-point Likert scale. The score for pain category ranges from 0 (no pain) to 20 (maximum pain); higher score indicates worse outcomes. Baseline is defined as the Day 0 value.
Stage A: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	Prior to second dose (Up to Day 180-Day 330)	Adverse events were collected from the time of informed consent through the last study visit on Day 360 (1 year). Treatment Emergent Adverse Events (TEAEs) occurred from the time of study drug treatment on Day 0 through end of study (Day 360) or early termination. This analysis reports any AEs/SAEs that occurred prior to the second dose.
Stage B: Number of Participants With AEs and SAEs	Post Second Dose (Day 180-Day 330 through Day 360)	Adverse events were collected from the time of informed consent through the last study visit on Day 360 (1 year). Treatment Emergent Adverse Events occurred from the time of study drug treatment on Day 0 through end of study (Day 360) or early termination. This analysis reports any AEs/SAEs that occurred after the second dose.

Secondary Outcome Measures

Name	Time	Method
Stage B: Change From Baseline in WOMAC Pain Score at Day 360	Day 360	The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score will be obtained from the Knee injury and Osteoarthritis Outcome Score (KOOS) questionnaire which is a validated, commonly used instrument to assess the participant's opinion about their knee and associated problems. Each item is answered on a 5-point Likert scale. The score for pain category ranges from 0 (no pain) to 20 (maximum pain); higher score indicates worse outcomes. Baseline is defined as the Day 0 value.
Stage B: Change From Baseline in WOMAC Function Score	At Day 360	The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function score will be obtained from the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire which is a is a validated, commonly used instrument to assess the participant's opinion about their knee and associated problems. Each item is answered on a 5-point Likert scale. The function dimension category asks about the degree of difficulty in doing 17 activities. The score ranges from 0 (normal function) to 170 (severely limited function); higher score indicates worse outcomes. Baseline is defined as the Day 0 value.
Stage A: Change From Baseline in Brief Pain Inventory (BPI) of Interference Score	Day 180	The Brief Pain Inventory (BPI) is a self-administered questionnaire for participants to rate the degree to which their pain interferes with common dimensions of feeling and function. The 7 pain interference items will be rated on 0-10 scale. Total interference score ranges from 0 (does not interfere) to 10 (completely interferes); higher score indicates worse outcomes.
Stage A: Change From Baseline in Patients Overall Assessment (POA)	Day 180	The Patient Overall Assessment (POA) is a self-administered questionnaire that records participants' responses to the question "Considering all the ways the OA in your knee affects you, how are you doing today?" on a scale of 1 to 5; 1 being very good (asymptomatic and no limitation of normal activities) to 5, very poor (very severe, intolerable symptoms and inability to carry out normal activities). Higher score indicates worse symptoms.
Stage A and B: Number of Participants With Presence of Anti-interleukin (IL)-10 Antibody	Up to Day 360	Presence of Immunoglobulin M (IgM) or Immunoglobulin G (IgG) antibodies against human IL-10 in serum was assessed at Baseline/Day 0 and then post-initial dose on Days 7, 30, 60, 180, and 360.

Trial Locations

Locations (6)

Neurovations (Napa Pain Institute); 🇺🇸 Napa, California, United States

eStudySite; 🇺🇸 La Mesa, California, United States

Carolinas Clinical Research Institute; 🇺🇸 Winston-Salem, North Carolina, United States

Source Healthcare; 🇺🇸 Santa Monica, California, United States

University of Adelaide in collaboration with CMAX Clinical Research Pty Ltd; 🇦🇺 Adelaide, South Australia, Australia

Alfred Health; 🇦🇺 Melbourne, Victoria, Australia