Safety of F14 Following Total Knee Replacement

• ClinicalTrials.gov Identifier: NCT04860635
• Recruitment Status: Suspended
• First Posted: April 27, 2021
• Last Update Posted: February 24, 2022
• Sponsor: Arthritis Innovation Corporation
• Information provided by (Responsible Party): Arthritis Innovation Corporation

Study Description

Brief Summary:

Open-label single-arm study in which all subjects receive F14 as part of a scheduled TKR and multimodal analgesia

Condition or disease	Intervention/treatment	Phase
Analgesia	Drug: F14 (sustained release celecoxib)	Phase 2; Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 100 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Open label
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open Label Safety Study of a Single Administration of F14 in Patients Undergoing Unilateral Total Knee Replacement
• Estimated Study Start Date: January 2023
• Estimated Primary Completion Date: May 2024
• Estimated Study Completion Date: May 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: F14 (sustained release celecoxib); Intra-articular F14 administration immediately following TKR surgery, and concurrent with multimodal standard of care analgesia	Drug: F14 (sustained release celecoxib); Celecoxib in BEPO® drug delivery system

Outcome Measures

Primary Outcome Measures :

1. Incidence and severity of treatment-emergent adverse events (TEAEs) [ Time Frame: From Day 0 to 12 months ]

Other Outcome Measures:

1. NRS pain intensity [ Time Frame: From Day 1 to 3 months ]
   Numerical rating scale (NRS); 11-point scale ranges from '0' representing "no pain" to '10' representing "worst imaginable pain"
2. Duration of need for walking aids [ Time Frame: From Day 1 to 3 months ]
3. Proportion of subjects using concomitant analgesics at any timepoint [ Time Frame: From Day 1 to 3 months ]
4. Celecoxib concentration in plasma [ Time Frame: At specified timepoints up to 3 months ]
   PK sub-study in 15 participants

Eligibility Criteria

• Ages Eligible for Study: 45 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Male and/or females indicated for primary, unilateral TKR
2. Between 45-80 years of age
3. Capable of giving signed informed consent
4. Body Mass Index (BMI) ≤ 40 kg/m2
5. Medically stable as determined by the Investigator, based on physical examination, clinical laboratory tests, and 12-lead ECG findings, as well as medical history from subject and pre-study source documents from other care providers
6. Absence of fixed flexion deformity exceeding 15deg
7. Absence of varus or valgus deformity exceeding 15deg
8. Minimum pre-operative flexion arc of 100deg
9. American Society of Anesthesiologists Physical Status Classification System (ASA-PSC) score ≤ 3
10. Females of childbearing potential with a negative serum pregnancy test at screening or males with a partner that is of childbearing potential, who agree to employ adequate birth control measures for the full duration of the study
11. Has undergone successful total knee replacement surgery, which in the opinion of the Investigator, will not affect the subject's study follow-up

Exclusion Criteria:

1. Known allergy or hypersensitivity to active ingredient celecoxib, OR known allergy or hypersensitivity to sulfonamide antibiotics or sulfa containing drugs when an allergy to celecoxib is unknown
2. Unwilling or unable to discontinue use of nonsteroidal anti-inflammatory drugs (NSAIDs) within 7 days of scheduled surgery, or medical marijuana or cannabidiol (CBD) within 10 days
3. Total or partial knee arthroplasty in the contralateral knee < 6 months prior to study surgery
4. Participation or scheduled participation in another clinical study involving an investigational drug or device within 30 days before screening or during study follow-up
5. Active or past infection in the index knee
6. Documented osteonecrosis of the index knee within previous 12 months
7. Other planned major surgery within 12 months of study surgery
8. Had a malignancy in the last year, except for non-metastatic basal cell or squamous cell carcinoma of the skin or localized carcinoma in situ of the cervix
9. Diagnosis of skin disorders including psoriasis, vascular insufficiency ulcers, and chronic venous stasis
10. History of coronary or vascular stent placed within 3 months
11. Suspected opioid abuse in the last 12 months with a score exceeding 5 on the DAST-10 questionnaire, and/or taking opioids on most days in the past three months, and currently taking >120 mg morphine equivalent dose (MED) at least 5 days per week in the month prior to screening
12. Current medical diagnosis or subject-reported seizure disorder
13. Current peripheral neuropathy
14. History of complex regional pain syndrome (CRPS)
15. Diagnosis of clinically significant liver hepatic and/or renal abnormalities within previous 2 years
16. Diagnosis of diabetes with HbA1c ≥7%
17. Current inflammatory arthritides (e.g., rheumatoid arthritis, lupus erythematosus, ankylosing spondylitis, psoriatic arthritis), or traumatic bone injuries within 12 months before scheduled surgery, except for clinically stable/non-active gout that does not affect the knee and does not interfere with walking
18. Treatment with immunosuppressants, antipsychotics, anticholinergics, or anticonvulsants within 1 month of intervention (antipsychotic stable dosage established for >30 days will be allowed)
19. Current or historical evidence of any clinically significant disease or condition, especially cardiovascular, pulmonary, or neurological
20. Participation in active or pending personal injury or workers' compensation litigation

Contacts and Locations

Locations

United States, Colorado

Panorama Orthopedics & Spine Center

Denver, Colorado, United States, 80401

United States, Texas

Endeavor Clinical Trials

San Antonio, Texas, United States, 78229

Sponsors and Collaborators

Arthritis Innovation Corporation

Investigators

• Principal Investigator: Jared Foran, MD; Panorama Orthopedics & Spine Center

More Information

• Responsible Party: Arthritis Innovation Corporation
• ClinicalTrials.gov Identifier: NCT04860635
• Other Study ID Numbers: 100-CIP03-P
• First Posted: April 27, 2021
• Last Update Posted: February 24, 2022
• Last Verified: July 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Arthritis Innovation Corporation:

total knee arthroplasty; postoperative pain; NSAID; multimodal analgesia

Additional relevant MeSH terms:

Celecoxib; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action