A Study to Evaluate the Safety and Efficacy of CNTX-6970 in Subjects With Knee Osteoarthritis Pain.
- Registration Number
- NCT05025787
- Lead Sponsor
- Maurizio Fava, MD
- Brief Summary
The primary objective of this study is to evaluate the safety and efficacy of CNTX-6970 for the treatment of pain related to OA of the knee compared to placebo. CNTX-6970 is being developed as a new treatment for chronic pain, including painful osteoarthritis of the knee.
- Detailed Description
The study will employ a randomized, allocation-concealed, multicenter, placebo-controlled, multi-period crossover design (Schmid et al, 2018). This multi-period crossover randomized, controlled trial allows comparability and assessment of efficacy through repeated exposures within each subject to the active treatment and a control (placebo) in randomized sequence. Such multi-period crossover designs are ideal for treatments with rapid onset of action and short half-life such as the asset under study here. We have strived to minimize the complexity of this powerful design by using only 2 blocks with 2 periods each. The modest additional complexity of the proposed multi-period crossover design, compared to a parallel-groups design, is justified by the marked improvement in efficiency. The gains in efficiency afforded by the multi-period crossover design allow a substantial reduction in sample size without sacrificing statistical power.
The trial will compare an active treatment vs. placebo. Each block will consist of two treatment periods with each period lasting 6 weeks. Treatment assignments (active drug versus placebo) will be randomized for each patient to the two periods within each block. The period length of 6 weeks was chosen based on several considerations: (i) Most efficacious analgesic drugs demonstrate separation from placebo by 6 weeks; (ii) The decision to move CNTX-6970 forward to Phase 3 will require a clinically meaningful separation from placebo by 6 weeks; (iii) In this Phase 2 study, implementing a treatment block longer than 6 weeks would make the overall design more challenging and burdensome by extending the duration of overall testing beyond 6 months; (iv).
In this study, the placebo will consist of inactive tablets identical to the active treatment tablets. Treatment assignments (active drug versus placebo) will be randomized for each patient to the two treatment periods within each block.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 77
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description 300mg BID CNTX-6970 The higher dose (i.e., 300mg BID) demonstrated good tolerability and safety, as well as over 90% inhibition of the binding of monocyte chemoattractant protein-1 to its CCR-2 receptor. Moreover, this dose produced nearly 90% binding inhibition at the CCR-5 receptor as well. Placebo Placebo Placebo
- Primary Outcome Measures
Name Time Method Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC-A) 24 Weeks The primary outcome measure used to assess efficacy will be patient-reported knee pain using the WOMAC Part A (Bellamy, et al., 1988).We will use the numerical rating scale version of the WOMAC, with the subject assessing each of 5 questions using an 11-point (0 to 10) scale; the total score is the sum of the individual item scores (range 0-50). A higher WOMAC score represents worse symptom severity.
Treatment emergent adverse events (TEAEs) 24 Weeks The primary safety endpoint is the incidence of treatment emergent adverse events (TEAEs), reported between the administration of study drug on Day 1 and the completion of the study at week 24 or early termination.
- Secondary Outcome Measures
Name Time Method Numeric Rating Scale (NRS) 24 Weeks Daily Knee Pain Intensity on a 0-10 Numeric Rating Scale (NRS). Pain intensity is reported by patients with chronic pain as one of the most important targets of treatment, and daily pain intensity ratings are a recommended core outcome measure for clinical trials of treatments for chronic pain. Daily ratings are preferable to ratings of recalled pain over longer time periods such as a week, as daily ratings minimize the influence of recall biases (Dworkin et al., 2005). Participants provide one-daily reports (at the end of the day) of their average knee pain intensity on a 0-10 pain intensity NRS over the course of a week, and those daily ratings are averaged to compute a mean knee pain intensity score. Participants will record their Daily Pain Intensity Numeric Rating Scale (NRS) 0-10 each day for one week prior to each clinic visit using NEForm.
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC-C) 24 Weeks WOMAC-C (Function subscale) (Bellamy et al, 1988). The WOMAC-physical function subscale contains 17 items assessing daily functioning, each using an 11-point (0 to 10) numerical rating scale. The total index score (0-170) is the sum of the items. A higher WOMAC function score represents worse functioning and less ability to engage in daily activities.
Hospital Anxiety and Depression Scale (HADS) 24 Weeks The HADS is a 14-item self-report questionnaire designed to assess symptoms of anxiety and depression in those with medical illness (Norton et al, 2013). This scale has 14 items, 7 related to anxiety and 7 to depression, rated on 4 points (0 to 3) in domains of intensity or frequency. Scoring is done separately for depression and for anxiety and each domain is interpreted as normal for scores of 0-7, borderline abnormal (borderline case) for scores of 8-10 and abnormal (case) for scores of 11-21. This scale is used to assess depression and anxiety in addition to HEAL/EPPIC-Net core data elements (CDEs) because of its higher sensitivity to change especially in patients with medical illnesses.
PROMIS Sleep Disturbance Scale - 6A 24 Weeks PROMIS Sleep Disturbance Scale - 6A (Yu et al, 2011). Sleep disruption has a bi-directional relationship with chronic pain and is an important secondary outcome to measure in pain trials (Edwards et al, 2016). The Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance short form is a convenient 6-item scale that correlates strongly with the longer forms. It shows greater measurement precision for assessing sleep disturbance than other commonly-used (and much longer) questionnaires such as the Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale; its brevity and convenience are a major advantage for both research and clinical settings (Yu et al, 2011). The PROMIS Sleep Disturbance Scale is expressed as a T-score, with a population mean of 50 and SD of 10. Possible T scores in this distribution range from 31.7 to 76.1.
Patient Global Impression of Change (PGIC) 24 Weeks The PGIC is a single-item measure of patient-reported improvement that is widely used as a general outcome measure in studies of chronic pain patients, including OA patients (Salaff et al, 2004). It is often used as an index of treatment-associated change, and patient-reported improvements in the form of PGIC scores correlate robustly with significant improvement in pain intensity, pain interference with activities of daily living, mood, and quality of life (Perrot and Lanteri-Minet, 2019).
Staircase-evoked pain assessment 24 Weeks This procedure consists of stepping fully up and down onto an 8in (20.32cm) high platform with both feet a total of 24 times. The lead leg is alternated between each up/down cycle. Subjects are instructed to use their normal gait for completing this task and are encouraged to complete the task despite increasing pain, without stopping if possible. The procedure is timed, and current knee pain intensity on a 0-10 Numeric Rating Scale (NRS) is assessed immediately before and following the procedure while the subject is in a seated, resting position.
Serum levels of cytokines and chemokines 24 Weeks These will be assessed at baseline and at the end of each treatment period (weeks 0, 6, 12, 18 and 24).Serum levels are measured in Picograms per millilitre (pg/mL). Serum analysis will include cytokines and chemokines as a part of establishing biomarker for treatment of OA pain with CNTX-6970.
MCP-1/CCR-2 24 Weeks Monocyte chemoattractant serum protein-1(MCP-1)/CCR-2 receptor binding inhibition by CNTX-6970. This will be assessed at baseline and at the end of each treatment period (weeks 0, 6, 12, 18 and 24). This test provides a single score, expressed as a percentage, 0-100%, with higher scores indicating more binding inhibition.
Trial Locations
- Locations (16)
University of Washington
🇺🇸Seattle, Washington, United States
M&M Clinical Trials
🇺🇸Miami, Florida, United States
New York University Langone Health
🇺🇸New York, New York, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Healthcare Research Network
🇺🇸Hazelwood, Missouri, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
UTsouthwestern Medical Center
🇺🇸Dallas, Texas, United States
University of California San Diego
🇺🇸La Jolla, California, United States
Icahn School of Medicine at Mount Sinai
🇺🇸New York, New York, United States
University of Pittsburgh
🇺🇸Pittsburgh, Pennsylvania, United States
University of Wisconsin- Madison
🇺🇸Madison, Wisconsin, United States
University of California- Davis
🇺🇸Sacramento, California, United States
Center for Clinical Research
🇺🇸Winston-Salem, North Carolina, United States
University of Florida
🇺🇸Gainesville, Florida, United States
University of Rochester
🇺🇸Rochester, New York, United States
Montefiore Medical Center
🇺🇸Bronx, New York, United States