Evaluate the Efficacy and Safety of ACP-044 in Subjects With Pain Associated With Osteoarthritis of the Knee

Study Overview
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Brief Summary
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To evaluate the efficacy of ACP-044 compared with placebo in the treatment of pain associated with osteoarthritis of the knee

Official Title
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A Phase 2, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of ACP-044 in Subjects With Pain Associated With Osteoarthritis of the Knee

Conditions
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Osteoarthritis Pain

Intervention / Treatment
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* Drug: ACP-044 Dose A
* Drug: ACP-044 Dose B
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects ≥18 and <65 years of age at the time of Screening Has a body mass index (BMI) ≤39 kg/m2 at Screening Confirmed history of pain associated with OA in the index knee Willing to maintain current activity and exercise levels throughout the study Willing and able to comply with clinic visits and study-related procedures Consent to allow all radiographs and medical/surgical/hospitalization records of care received elsewhere to be shared with the Investigator and third parties who will examine the images (i.e., central x-ray reader) Exclusion Criteria: Pain anywhere else in the body which is greater than or equal to OA pain in the index knee, or likely to interfere with subject's assessment of pain throughout the study, as judged by the Investigator History or presence on imaging of knee arthropathy (osteonecrosis, subchondral insufficiency fracture, rapidly progressive OA type 1 or type 2), recent fall, injury, or trauma affecting the index knee, ligament tear, neuropathic joint arthropathy, knee dislocation (patella dislocation is eligible), extensive subchondral cysts, Baker's cyst, evidence of bone fragmentation or collapse, or primary metastatic tumor with the exception of chondromas, or pathological fractures during the Screening Period History or presence at Screening of non-OA inflammatory joint disease (e.g., rheumatoid arthritis, lupus erythematosus, psoriatic arthritis, pseudo-gout, gout, spondyloarthropathy, joint infections within the past 5 years, Paget's disease of the spine, pelvis, or femur, neuropathic disorders, multiple sclerosis, fibromyalgia, tumors or infections of the spinal cord, or renal osteodystrophy) or any condition that would interfere with the rating of OA pain Recent arthroscopic surgery within 1 month of Screening; or has any planned surgery or procedure during the study Use of monoamine reuptake inhibitors, tricyclic antidepressants, anticonvulsants, and/or serotonin norepinephrine reuptake inhibitors within 4 weeks prior to Screening Unwilling to discontinue current use of analgesic medication following Screening and to adhere to study requirements for rescue treatments (study-provided acetaminophen to be taken as needed with a maximum daily dose of 2500 mg), including, but not limited to, nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, selective cyclooxygenase 2 inhibitors, acetaminophen, or combinations thereof, within 7 days or five half-lives of the drug prior to the Baseline Pain Assessment Period, whichever is longer Use of immediate- or extended-release or controlled-release opioids (e.g., oxycontin), transdermal fentanyl, or methadone within 3 months prior to Screening Use of opioids, for the treatment of pain other than OA of the knee, with a morphine equivalent dose of ≥30 mg per day for more than 2 days per week within 1 month prior to Screening Use of systemic (i.e., oral) corticosteroids or intra-articular corticosteroids in any joint within 30 days prior to the screening visit (topical, intranasal, and inhaled corticosteroids are permitted) Intra-articular injection of any approved (i.e., hyaluronic acid and corticosteroids) or unapproved treatments (e.g., platelet-rich plasma, capsaicin) into the index knee within 3 months of Screening Physical/occupational/chiropractic therapy for the lower extremities or acupuncture for the lower extremities within 30 days of Screening, or the need for such therapy during the study Has current evidence, or history within the previous 12 weeks prior to Screening, of a serious and/or unstable psychiatric, neurologic, cardiovascular, respiratory, gastrointestinal, renal, hepatic, hematologic, endocrinologic, or other medical disorder, that in the judgment of the Investigator and/or Medical Monitor would jeopardize the safe participation of the subject in the study Had a malignancy in the last year, with the exception of nonmetastatic basal cell of the skin or localized carcinoma in situ of the cervix Additional inclusion/exclusion criteria apply. Patients will be evaluated at screening to ensure that all criteria for study participation are met. Patients may be excluded from the study based on these assessments (and specifically, if it is determined that their baseline health and psychiatric condition do not meet all pre-specified entry criteria).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Drug - ACP-044 Dose A<br>ACP-044 Dose A | Drug: ACP-044 Dose A<br>* Oral dose of ACP-044 Dose A<br>|
| Experimental: Drug - ACP-044 Dose B<br>ACP-044 Dose B | Drug: ACP-044 Dose B<br>* Oral dose of ACP-044 Dose B<br>|
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline to Week 4 in the weekly average of the daily average Numeric Rating Scale (NRS) pain intensity scores. | The 0-10 NRS consists in a single 11-point numeric scale, with 0 indicating no pain at all and 10 reflecting the worst pain imaginable. | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient Global Impression of Change (PGIC) at Week 4 with reference to baseline status. | PGIC is a 7-point scale depicting a subject's rating of overall improvement. Subjects rate their change as very much improved, much improved, minimally improved, no change, minimally worse, much worse, or very much worse. | 4 weeks | 
| Change from Baseline to Week 4 in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score and individual subscale scores for pain, stiffness, and physical function. | WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in knee joint during past 48 hours. Score range is 0 (no pain) to 20 (worst pain), where higher scores indicated higher pain. WOMAC physical function subscale is a 17-item questionnaire used to assess the degree of difficulty experienced due to osteoarthritis in knee joint during past 48 hours. Score range is 0 to 68, where higher scores indicate worse function. WOMAC stiffness subscale is a 2-item questionnaire used to assess the amount of stiffness experienced due to osteoarthritis in knee joint during past 48 hours. Score range is 0 (minimum stiffness) to 8 (maximum stiffness). WOMAC Total score is the mean of WOMAC pain, physical function and stiffness subscale scores and ranges from 0 (no pain) to 96 (worst possible pain), where higher score indicates worse response. | 4 weeks | 
| Proportion of subjects who are responders as defined by 30% and 50% reduction from Baseline to Week 4 in the weekly average of the daily average NRS pain intensity scores |  | 4 weeks | 
| Change from Baseline to Week 4 in weekly average of the daily worst NRS pain intensity scores. | The 0-10 NRS consists in a single 11-point numeric scale, with 0 indicating no pain at all and 10 reflecting the worst pain imaginable. | 4 weeks | 
| Change from Baseline to Week 4 in Brief Pain Inventory-Short Form (BPI-sf). | The BPI-SF is a self-administered, validated tool for the assessment of severity of pain and the impact of pain on daily functions, location of pain, pain medications, and amount of pain relief in the last week. The BPI-SF uses a numeric rating scale (NRS) from 0 to 10, lower score denotes less severity and impact, higher score denotes more severity and impact. | 4 weeks | 
| Change from Baseline to Week 4 in 12-item Short Form Survey (SF-12). | The SF-12 is a 12-item health survey instrument that is used to evaluate the subject's physical, social, and mental well-being. Results are expressed in terms of 2 composite scores: the Physical Component Scale (PCS) and the Mental Component Summary (MCS). PCS and MCS values can range from 0 to 100. Lowest scores mean very much below and highest scores mean very much above the general population average. | 4 weeks |