A Study to Evaluate the Safety and Efficacy of CNTX-6970... | NCT05025787 | Trialant
NCT05025787
Sponsor
Maurizio Fava, MD
Status
Completed
Last Update Posted
Nov 26, 2025Actual
Enrollment
55Actual
Phase
Phase 2
Conditions
Knee Osteoarthritis
Interventions
CNTX-6970
Placebo
Countries
United States
Protocol Section
Identification Module
NCT ID
NCT05025787
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
2021p002273 (EN20-01)
Secondary IDs
Not provided
Brief Title
A Study to Evaluate the Safety and Efficacy of CNTX-6970 in Subjects With Knee Osteoarthritis Pain.
Official Title
EN20-01: A 24 Week Study to Evaluate the Safety and Efficacy of CNTX-6970 in Subjects With Moderate to Severe Knee Osteoarthritis Pain.
Acronym
Not provided
Organization
Massachusetts General HospitalOTHER
Status Module
Record Verification Date
Nov 2025
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Oct 25, 2021Actual
Primary Completion Date
Jun 11, 2024Actual
Completion Date
Jun 11, 2024Actual
First Submitted Date
Aug 16, 2021
First Submission Date that Met QC Criteria
Aug 23, 2021
First Posted Date
Aug 27, 2021Actual
Results Waived
Not provided
Results First Submitted Date
Jun 4, 2025
Results First Submitted that Met QC Criteria
Nov 13, 2025
Results First Posted Date
Nov 26, 2025Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Nov 13, 2025
Last Update Posted Date
Nov 26, 2025Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Maurizio Fava, MD, Psychiatrist in Chief, Massachusetts General HospitalSponsor-Investigator
Lead Sponsor
Maurizio Fava, MDOTHER
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
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.
Conditions Module
Conditions
Knee Osteoarthritis
Keywords
Not provided
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
55Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
300mg BID CNTX-6970, Then Placebo
Experimental
Participants initially received 300 mg BID of CNTX-6970 for 6 weeks (Block 1, Period 1). Following this, they were administered matching placebo BID for another 6 weeks (Block 1, Period 2). After a total of 12 weeks, participants received 300 mg BID of CNTX-6970 again for 6 weeks (Block 2, Period 1). Finally, after 18 weeks of total treatment, participants received a matching placebo for an additional 6 weeks (Block 2, Period 2), completing a 24-week study period.
Drug: CNTX-6970
Drug: Placebo
Placebo, then 300 mg BID CNTX-6970
Placebo Comparator
Participants initially received placebo BID for 6 weeks (Block 1, Period 1). Following this, they were administered 300 mg CNTX-9670 BID for another 6 weeks (Block 1, Period 2). After a total of 12 weeks, participants received placebo BID again for 6 weeks (Block 2, Period 1). Finally, after 18 weeks of total treatment, participants received a 300 mg CNTX-6970 BID for an additional 6 weeks (Block 2, Period 2), completing a 24-week study period.
Drug: CNTX-6970
Drug: Placebo
Interventions
Name
Type
Description
Arm Group Labels
Other Names
CNTX-6970
Drug
CNTX-6970, a novel potent antagonist of CCR2 with lesser effects on CCR5, is being developed as a new treatment for chronic pain, including painful osteoarthritis of the knee.
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC-A)
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.
24 Weeks
Treatment Emergent Adverse Events (TEAEs)
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.
24 Weeks
Secondary Outcomes
Measure
Description
Time Frame
Numeric Rating Scale (NRS)
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. Lower NRS values correspond to less pain.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
A subject will be eligible for study participation if they meet all of the following criteria:
Individuals between 40 and 90 years of age (inclusive) at the time of the Screening Visit.
Willing to use a mobile smart device during the study period. Individuals who do not have access to a mobile device will be provided with one for the duration of the study and trained in its use.
Can understand the nature of the study and protocol requirements and is willing to comply with study drug administration requirements and discontinue prohibited concomitant medications.
Radiography of both knees with a posterior-anterior, fixed-flexion view taken during the Screening visit. The Index knee must show evidence of chronic OA with a K-L Grading Scale of 1, 2, 3, or 4. Such evidence will be provided by a central reading of the radiography of both knees from an expert radiologist of the CCC of EPPIC-Net.
Moderate to severe pain in the Index knee associated with OA and stable for a minimum of 6 months prior to Screening in the opinion of the investigator.
Confirmation of OA of the index knee: American College of Rheumatology (ACR) diagnostic criteria.
Subjects must have failed 2 or more prior therapies. Failure is deemed to be inadequate relief in the opinion of the investigator.
Body mass index (BMI) of ≤ 40 kg/m2.
Willing to refrain from illicit drug use during the study, and to have illicit drug testing at screening and at later time points.
A subject will be excluded from the study if they meet any of the following criteria:
Any form of joint replacement surgery, open surgery, or arthroscopic surgery of the index knee/knee joint with 12 months of Screening.
Any painful condition(s) of the index knee due to disease other than OA. For example, periarticular or referred pain involving the index knee, or from joint disease other than OA associated with the index knee.
Other chronic pain anywhere in the lower extremities (e.g. hips, legs, feet) that is equal or greater in intensity or impairment than index knee pain or that requires the use of analgesic medications. This includes radicular low back pain with radiation to the knee.
Documented history of neuropathic arthropathy in the knee.
Significant instability (e.g., cruciate ligament tear or rupture or previous repair) within the past 5 years or current misalignment (>10 degrees varus or valgus) of the index knee.
Plans to have surgery, invasive procedures, or intra-articular (IA) injections of the index knee or procedure or surgery otherwise contraindicated for study participation while in the study.
a. Concomitant Medications for Pain - i. Continuous use of one of the following medications prescribed for pain: tramadol, gabapentin, duloxetine, pregabalin, milnacipran, or tricyclic antidepressants that is:
chronic for at least 12 weeks; and
at a stable dose for at least 4 weeks before Screening ii. Intermittent use of opioids that is:
ongoing for at least 4 weeks before Screening;
at a frequency no more than 4 days/week; and
not be taken within 24 hours of a study visit
iii. As needed use of acetaminophen iv. Continuous use of medical marijuana (or equivalent) that is chronic for at least 12 weeks and at a stable dose for 4 weeks v. Topical creams (includes CBD topicals)
Continuous use allowed if chronic and stable for at least 12 weeks
Intermittent use allowed if at a frequency of no more than 4 days/week
b. Concomitant Medications for Non-Pain Indications That May Impact Pain - i. Continuous use of medication for non-pain indications that are known to potentially impact pain, e.g. duloxetine for depression, that is at a stable dose for at least 12 weeks prior to Screening.
ii. Low-dose aspirin for the purposes of heart disease prophylaxis
Corticosteroid injection in the index knee within 30 days of Screening or during study participation (unless the injectable is a long-acting agent such as triamcinolone acetonide extended-release injectable suspension (Zilretta) in which case the injection cannot be within 90 days of screening).
Received IA viscosupplementation (e.g., Synvisc®, Hyalgan®) within 90 days of Screening.
10. Use of an investigational medication within 30 days of Screening, or 5 pharmacokinetic or pharmacodynamic half-lives (whichever is longer) or scheduled to receive such an agent while participating in the current study.
11. Current therapy with any immunosuppressive therapy, including corticosteroids (>5 mg/day of prednisone).
Arnold SE, Betensky RA. Multicrossover Randomized Controlled Trial Designs in Alzheimer Disease. Ann Neurol. 2018 Aug;84(2):168-175. doi: 10.1002/ana.25280. Epub 2018 Aug 29.
Arroll B, Goodyear-Smith F, Crengle S, Gunn J, Kerse N, Fishman T, Falloon K, Hatcher S. Validation of PHQ-2 and PHQ-9 to screen for major depression in the primary care population. Ann Fam Med. 2010 Jul-Aug;8(4):348-53. doi: 10.1370/afm.1139.
See Also Links
Not provided
Available IPD Information
Not provided
IPD Sharing Statement Module
Plan to Share IPD
Yes
Description
The EPPIC-Net DCC's NYU Center for Biospecimen Research and Development (CBRD) will store and manage biological samples (biosamples) collected in this clinical trial. The samples will be used for the present study and also for potential future research as permitted by the study-specific informed consent form. Biosamples stored for this study may include, but are not limited to: whole blood, plasma, stool, synovial fluid, and/or derivatives of these specimens. The samples will be stored only for the period defined in the informed consent form, which may be indefinite. Biospecimens may be shared in accordance with the protocol-defined data and sample sharing plan and the informed consent form.
Biosamples will be documented in LabVantage, a secure network linking biospecimens to corresponding clinical and pathological data. LabVantage does not include any identifying personal health information (PHI). The CBRD and LabVantage meet all General Lab Protocol (GLP) and FDA guidelines.
Types
Informed Consent Form (ICF)
Time Frame
Not provided
Access Criteria
Not provided
URL
Not provided
Results Section
Participant Flow Module
Pre-assignment Details
Not provided
Recruitment Details
Not provided
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
300mg BID, Then Placebo
Participants initially received 300 mg BID of CNTX-6970 for 6 weeks (Block 1, Period 1). Following this, they were administered matching placebo BID for another 6 weeks (Block 1, Period 2). After a total of 12 weeks, participants received 300 mg BID of CNTX-6970 again for 6 weeks (Block 2, Period 1). Finally, after 18 weeks of total treatment, participants received matching placebo for an additional 6 weeks (Block 2, Period 2), completing a 24-week study period.
Periods
Title
Milestones
Reasons Not Completed
Overall Study
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
0
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
Large Document Module
Document Has No Statistical Analysis Plan (SAP)
Not provided
Uploaded Document Information
Type
Includes Protocol
Includes SAP
Includes ICF
Document Label
Document Date
Document Uploaded Date
Document File Name
Prot
Yes
No
No
Study Protocol
Jan 22, 2024
Jul 2, 2025
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Not provided
Submission Tracking
Estimated Results First Submitted Date
Not provided
Condition Browse Module
MeSH Terms
Intervention Browse Module
No data available
No data is available for this block.
Randomized
Intervention Model
Crossover Assignment
Intervention Model Description
The study will employ a randomized, allocation-concealed, multicenter, placebo-controlled, multi-period crossover design.
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
Quadruple
Masking Description
Blinding of the randomization assignment from trial subjects, staff from the Clinical Sites, CCC, and DCC will be ensured through the use of the IXRS.
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC-C)
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.
24 Weeks
Hospital Anxiety and Depression Scale (HADS) - Anxiety
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.
24 Weeks
Patient Global Impression of Change (PGIC)
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).
The PCIC was collected at baseline and week 24. PGIC is scored from 0-6, where lower values correspond to better outcomes (e.g., 0 = very much improved, whereas 6 is very much worse).
24 Weeks
Serum Levels of Cytokines and Chemokines
Assessed at baseline and at the end of each treatment period (weeks 6, 12, 18, and 24).Serum levels are measured in Picograms per millilitre (pg/mL). Analyses were performed for Aim 5 to assess the efficacy of CNTX-6970 (300mg BID) in comparison to placebo in biomarkers from (b) serum and synovial fluid levels of chemokines and cytokines; and (c) Synovial monocyte chemoattractant protein-1/CCR-2 receptor binding inhibition in blood and synovial fluid.
The following 9 biomarkers had sufficient data based on either the ability to fit models A and/or B and at least 50% of the values were above the minimum detectable threshold:
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 6, 12, 18 and 24).
The data is measured in pg per mL, the data in analyzed in the natural log of pg per mL, with higher numbers indicating more binding inhibition.
24 Weeks
Hospital Anxiety and Depression Scale (HADS) - Depression
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.
24 Weeks
PROMIS - 6A
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). 60 is the most commonly used threshold for clinically significant sleep. The PROMIS Sleep Disturbance Scale is expressed as a T-score, with a population mean of 50 and SD of 10. A higher T-score indicates better physical functioning. Possible T scores in this distribution range from 31.7 to 76.1.
24 Weeks
Staircase-evoked Pain Assessment
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. Lower values correspond to less pain.
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Background
Centrexion Investigator's Brochure for CNTX-6970. Version 2, 21 February 2019.
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Background
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Osani MC, Vaysbrot EE, Zhou M, McAlindon TE, Bannuru RR. Duration of Symptom Relief and Early Trajectory of Adverse Events for Oral Nonsteroidal Antiinflammatory Drugs in Knee Osteoarthritis: A Systematic Review and Meta-Analysis. Arthritis Care Res (Hoboken). 2020 May;72(5):641-651. doi: 10.1002/acr.23884. Epub 2020 Apr 14.
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Background
Schmid CH, Duan N. Statistical design and analytic considerations for N-of-1 trials. Design and Implementation of N-of-1 Trials: A User's Guide Rockville, MD: Agency for Healthcare Research and Quality; 2014. p. 33-52.
Background
Sullivan MJL, Bishop S, Pivik J. The pain catastrophizing scale: development and validation. Psychol Assess 1995; 7: 432-524.
Timmermans EJ, de Koning EJ, van Schoor NM, van der Pas S, Denkinger MD, Dennison EM, Maggi S, Pedersen NL, Otero A, Peter R, Cooper C, Siviero P, Castell MV, Herbolsheimer F, Edwards M, Limongi F, Deeg DJH, Schaap LA. Within-person pain variability and physical activity in older adults with osteoarthritis from six European countries. BMC Musculoskelet Disord. 2019 Jan 5;20(1):12. doi: 10.1186/s12891-018-2392-0.
Treister R, Honigman L, Lawal OD, Lanier RK, Katz NP. A deeper look at pain variability and its relationship with the placebo response: results from a randomized, double-blind, placebo-controlled clinical trial of naproxen in osteoarthritis of the knee. Pain. 2019 Jul;160(7):1522-1528. doi: 10.1097/j.pain.0000000000001538.
Treister R, Suzan E, Lawal OD, Katz NP. Staircase-evoked Pain May be More Sensitive Than Traditional Pain Assessments in Discriminating Analgesic Effects: A Randomized, Placebo-controlled Trial of Naproxen in Patients With Osteoarthritis of the Knee. Clin J Pain. 2019 Jan;35(1):50-55. doi: 10.1097/AJP.0000000000000651.
Background
van Buuren S, Groothuis-Oudshoorn K. Multivariate Imputation by Chained Equations in R. Journal of Statistical Software, 2011, 45(3), 1-67.
Wasan AD, Alter BJ, Edwards RR, Argoff CE, Sehgal N, Walk D, Moeller-Bertram T, Wallace MS, Backonja M. Test-Retest and Inter-Examiner Reliability of a Novel Bedside Quantitative Sensory Testing Battery in Postherpetic Neuralgia Patients. J Pain. 2020 Jul-Aug;21(7-8):858-868. doi: 10.1016/j.jpain.2019.11.013. Epub 2019 Dec 11.
Yu L, Buysse DJ, Germain A, Moul DE, Stover A, Dodds NE, Johnston KL, Pilkonis PA. Development of short forms from the PROMIS sleep disturbance and Sleep-Related Impairment item banks. Behav Sleep Med. 2011 Dec 28;10(1):6-24. doi: 10.1080/15402002.2012.636266.
Zucker DR, Schmid CH, McIntosh MW, D'Agostino RB, Selker HP, Lau J. Combining single patient (N-of-1) trials to estimate population treatment effects and to evaluate individual patient responses to treatment. J Clin Epidemiol. 1997 Apr;50(4):401-10. doi: 10.1016/s0895-4356(96)00429-5.
Edwards RR, Tarpey T, Ashburn M, Baer C, Campbell A, Dworkin RH, Gaspard G, Flynn M, Hade E, Jain N, Judge H, Kamp C, Li Y, Meropol S, Petkova E, Philip A, Przkora R, Rathmell JP, Robinson-Papp J, Samuels J, Sehgal N, Sienty J, Stacey B, Wallace M, Wasan AD, Wise B, Yu C, Fava M, Troxel AB. A double-blind, placebo-controlled, multi-crossover trial of treatment with a chemokine antagonist for knee osteoarthritis pain. Pain. 2026 May 1;167(5):1137-1145. doi: 10.1097/j.pain.0000000000003904. Epub 2026 Jan 6.
FG001
Placebo, Then 300 mg CNTX-6970 BID
Participants initially received placebo BID for 6 weeks (Block 1, Period 1). Following this, they were administered CNTX-6970 BID for another 6 weeks (Block 1, Period 2). After a total of 12 weeks, participants received placebo BID again for 6 weeks (Block 2, Period 1). Finally, after 18 weeks of total treatment, participants received CNTX-6970 BID for an additional 6 weeks (Block 2, Period 2), completing a 24-week study period.
FG00028 subjects
FG00127 subjectsMulti-crossover study, all participants were randomized to recieve 300 mg CNTX-9670 BID and Placebo
COMPLETED
FG00019 subjects
FG00118 subjectsMulti-crossover study, all participants were randomized to recieve 300 mg CNTX-9670 BID and Placebo
NOT COMPLETED
FG0009 subjects
FG0019 subjects
Type
Comment
Reasons
Lack of Efficacy
FG0000 subjects
FG0011 subjects
Adverse Event
FG0002 subjects
FG0014 subjects
Non compliance
FG0000 subjects
FG0011 subjects
Protocol Violation
FG0003 subjects
FG0011 subjects
Stopping criteria met
FG0001 subjects
FG0011 subjects
Withdrawal by Subject
FG0003 subjects
FG0011 subjects
Intension-to-Treat (ITT) - All randomized participants
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
300mg BID, Then Placebo (DPPD)
Participants initially received 300 mg BID of CNTX-6970 for 6 weeks (Block 1, Period 1). Following this, they were administered matching placebo BID for another 6 weeks (Block 1, Period 2). After a total of 12 weeks, participants received 300 mg BID of CNTX-6970 again for 6 weeks (Block 2, Period 1). Finally, after 18 weeks of total treatment, participants received matching placebo for an additional 6 weeks (Block 2, Period 2), completing a 24-week study period.
BG001
Placebo, Then 300 mg CNTX-6970 BID (PDDP)
Participants initially received placebo BID for 6 weeks (Block 1, Period 1). Following this, they were administered CNTX-6970 BID for another 6 weeks (Block 1, Period 2). After a total of 12 weeks, participants received placebo BID again for 6 weeks (Block 2, Period 1). Finally, after 18 weeks of total treatment, participants received CNTX-6970 BID for an additional 6 weeks (Block 2, Period 2), completing a 24-week study period.
BG002
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00028
BG00127
BG00255
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Categorical
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
<=18 years
BG0000
BG0010
BG0020
Between 18 and 65 years
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG00021
BG00122
BG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Hispanic or Latino
BG0009
BG0015
BG002
Race (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
American Indian or Alaska Native
BG0000
BG0010
BG002
Region of Enrollment
Number
participants
Title
Denominators
Categories
United States
Title
Measurements
BG00028
BG00127
BG002
Moderate to severe knee pain stable for 6 months
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
BG00028
BG00127
BG002
Confirmation of Knee OA by central radiologist
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
BG00028
BG00127
BG002
Two or more failed therapies
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
BG00028
BG00127
BG002
mid-high lain score as defined by the WOMAC-A and NRSs
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
BG00028
BG00127
BG002
BMI less than or equal to 40
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
BG00028
BG00127
BG002
Compliant with study requirements before the baseline visit
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
BG00028
BG00127
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC-A)
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.
Intension-to-Treat (ITT) - All randomized participants
Posted
Mean
Standard Deviation
Score on a scale
24 Weeks
ID
Title
Description
OG000
300mg BID CNTX-6970 (DPPD): B1P1
Block 1 Period 1: Participants were instructed to take 300 mg CNTX-6970 BID for weeks 1 through 6
OG001
Placebo BID (DPPD): B1P2
Block 1 Period 2: Participants were instructed to take matching placebo BID for weeks 6 through 12
OG002
Placebo BID (PDDP): B1P1
Block 1 Period 1: Participants were instructed to take matching placebo BID for weeks 1 through 6
OG003
300 mg BID CNTX-6970 (PDDP): B1P2
Block 1 Period 2: Participants were instructed to take 300 mg CNTX-6970 BID for weeks 6 through 12
OG004
Placebo BID (DPPD): B2P1
Block 2 Period 1: Participants were instructed to take matching placebo BID for weeks 12 through 18
OG005
300 mg CNTX-6970 (DPPD): B2P2
Block 2 Period 2: Participants were instructed to take 300 mg CNTX-6970 BID for weeks 18 through 24
OG006
300 mg CNTX-6970 BID (PDDP): B2P1
Block 2 Period 1: Participants were instructed to take 300 mg CNTX-6970 BID for weeks 12 through 18
OG007
Placebo BID (PDDP): B2P2
Block 2 Period 2: Participants were instructed to take matching Placebo BID for weeks 18 through 24
Units
Counts
Participants
OG00026
OG00121
OG00223
OG003
Title
Denominators
Categories
Title
Measurements
OG00022.5± 12.5
OG00118.6± 12.5
OG00218.9± 10.1
OG003
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
OG002
OG003
OG004
OG005
OG006
OG007
Null hypothesis is that there was no difference in mean WOMAC-A pain between CNTX-6970 and Placebo. Linear mixed-effect models were used with block, period, sex, age, and KL-grade as covariates and treatment group as factor, with random effects for sites and subjects nested within sites. The test was performed with significance level of 0.05 (two-sided).
Power was computed for effect sizes ranging from 0.25 to 0.50 using Monte Carlo simulation, and exceeded 80%.
Mixed Models Analysis
.006
A 95% confidence interval for the treatment coefficient in the linear mixed-effect model was (-3.033, -0.514), where the reference level was the active treatment.
model treatment coefficient
-1.774
Standard Deviation
0.639
2-Sided
95
-3.033
-0.514
Primary
Treatment Emergent Adverse Events (TEAEs)
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.
Intension-to-Treat (ITT) - All randomized participants
Posted
Count of Participants
Participants
24 Weeks
ID
Title
Description
OG000
300mg BID CNTX-6970 (DPPD): B1P1
Block 1 Period 1: Participants were instructed to take 300 mg CNTX-6970 BID for weeks 1 through 6
OG001
Placebo BID (DPPD): B1P2
Block 1 Period 2: Participants were instructed to take matching placebo BID for weeks 6 through 12
OG002
Placebo BID (PDDP): B1P1
Block 1 Period 1: Participants were instructed to take matching placebo BID for weeks 1 through 6
OG003
300 mg BID CNTX-6970 (PDDP): B1P2
Block 1 Period 2: Participants were instructed to take 300 mg CNTX-6970 BID for weeks 6 through 12
Secondary
Numeric Rating Scale (NRS)
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. Lower NRS values correspond to less pain.
Intension-to-Treat (ITT) - All randomized participants
Posted
Mean
Standard Deviation
units on a scale
24 Weeks
ID
Title
Description
OG000
300mg BID CNTX-6970 (DPPD): B1P1
Block 1 Period 1: Participants were instructed to take 300 mg CNTX-6970 BID for weeks 1 through 6
OG001
Placebo BID (DPPD): B1P2
Block 1 Period 2: Participants were instructed to take matching placebo BID for weeks 6 through 12
OG002
Secondary
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC-C)
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.
Intension-to-Treat (ITT) - All randomized participants
Posted
Mean
Standard Deviation
units on a scale
24 Weeks
ID
Title
Description
OG000
300mg BID CNTX-6970 (DPPD): B1P1
Block 1 Period 1: Participants were instructed to take 300 mg CNTX-6970 BID for weeks 1 through 6
OG001
Placebo BID (DPPD): B1P2
Block 1 Period 2: Participants were instructed to take matching placebo BID for weeks 6 through 12
OG002
Placebo BID (PDDP): B1P1
Block 1 Period 1: Participants were instructed to take matching placebo BID for weeks 1 through 6
OG003
300 mg BID CNTX-6970 (PDDP): B1P2
Secondary
Hospital Anxiety and Depression Scale (HADS) - Anxiety
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.
Participants initially received placebo BID for 6 weeks (Block 1, Period 1). Following this, they were administered CNTX-6970 BID for another 6 weeks (Block 1, Period 2). After a total of 12 weeks, participants received placebo BID again for 6 weeks (Block 2, Period 1). Finally, after 18 weeks of total treatment, participants received CNTX-6970 BID for an additional 6 weeks (Block 2, Period 2), completing a 24-week study period.
Posted
Mean
Standard Deviation
units on a scale
24 Weeks
ID
Title
Description
OG000
300mg BID CNTX-6970 (DPPD): B1P1
Block 1 Period 1: Participants were instructed to take 300 mg CNTX-6970 BID for weeks 1 through 6
OG001
Placebo BID (DPPD): B1P2
Block 1 Period 2: Participants were instructed to take matching placebo BID for weeks 6 through 12
Secondary
Patient Global Impression of Change (PGIC)
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).
The PCIC was collected at baseline and week 24. PGIC is scored from 0-6, where lower values correspond to better outcomes (e.g., 0 = very much improved, whereas 6 is very much worse).
Intension-to-Treat (ITT) - All randomized participants
Posted
Mean
Standard Deviation
units on a scale
24 Weeks
ID
Title
Description
OG000
Placebo BID (PDDP): B2P2
Block 2 Period 2: Participants were instructed to take matching Placebo BID for weeks 18 through 24
OG001
300 mg CNTX-6970 (DPPD): B2P2
Block 2 Period 2: Participants were instructed to take 300 mg CNTX-6970 BID for weeks 18 through 24
Units
Counts
Secondary
Serum Levels of Cytokines and Chemokines
Assessed at baseline and at the end of each treatment period (weeks 6, 12, 18, and 24).Serum levels are measured in Picograms per millilitre (pg/mL). Analyses were performed for Aim 5 to assess the efficacy of CNTX-6970 (300mg BID) in comparison to placebo in biomarkers from (b) serum and synovial fluid levels of chemokines and cytokines; and (c) Synovial monocyte chemoattractant protein-1/CCR-2 receptor binding inhibition in blood and synovial fluid.
The following 9 biomarkers had sufficient data based on either the ability to fit models A and/or B and at least 50% of the values were above the minimum detectable threshold:
Per Protocol: All randomized participants excluding participants with major protocol deviations. Major protocol deviations are those with early terminated from the study and those who had inclusion/exclusion criteria deviation or a treatment dispensing error judged to be significant by study leadership. In this study, only one participant had a treatment dispending error.
Posted
Mean
Standard Deviation
log(pg/mL)
24 Weeks
ID
Title
Description
OG000
300mg BID CNTX-6970 (DPPD): B1P1
Block 1 Period 1: Participants were instructed to take 300 mg CNTX-6970 BID for weeks 1 through 6
OG001
Placebo BID (DPPD): B1P2
Secondary
MCP-1/CCR-2
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 6, 12, 18 and 24).
The data is measured in pg per mL, the data in analyzed in the natural log of pg per mL, with higher numbers indicating more binding inhibition.
ITT - Intention to Treat
Posted
Mean
Standard Deviation
natural log(pg/mL)
24 Weeks
ID
Title
Description
OG000
300mg BID CNTX-6970 (DPPD): B1P1
Block 1 Period 1: Participants were instructed to take 300 mg CNTX-6970 BID for weeks 1 through 6
OG001
Placebo BID (DPPD): B1P2
Block 1 Period 2: Participants were instructed to take matching placebo BID for weeks 6 through 12
OG002
Placebo BID (PDDP): B1P1
Block 1 Period 1: Participants were instructed to take matching placebo BID for weeks 1 through 6
OG003
300 mg BID CNTX-6970 (PDDP): B1P2
Block 1 Period 2: Participants were instructed to take 300 mg CNTX-6970 BID for weeks 6 through 12
Secondary
Hospital Anxiety and Depression Scale (HADS) - Depression
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.
Participants initially received placebo BID for 6 weeks (Block 1, Period 1). Following this, they were administered CNTX-6970 BID for another 6 weeks (Block 1, Period 2). After a total of 12 weeks, participants received placebo BID again for 6 weeks (Block 2, Period 1). Finally, after 18 weeks of total treatment, participants received CNTX-6970 BID for an additional 6 weeks (Block 2, Period 2), completing a 24-week study period.
Posted
Mean
Standard Deviation
units on a scale
24 Weeks
ID
Title
Description
OG000
300mg BID CNTX-6970 (DPPD): B1P1
Block 1 Period 1: Participants were instructed to take 300 mg CNTX-6970 BID for weeks 1 through 6
OG001
Placebo BID (DPPD): B1P2
Block 1 Period 2: Participants were instructed to take matching placebo BID for weeks 6 through 12
Secondary
PROMIS - 6A
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). 60 is the most commonly used threshold for clinically significant sleep. The PROMIS Sleep Disturbance Scale is expressed as a T-score, with a population mean of 50 and SD of 10. A higher T-score indicates better physical functioning. Possible T scores in this distribution range from 31.7 to 76.1.
Participants initially received placebo BID for 6 weeks (Block 1, Period 1). Following this, they were administered CNTX-6970 BID for another 6 weeks (Block 1, Period 2). After a total of 12 weeks, participants received placebo BID again for 6 weeks (Block 2, Period 1). Finally, after 18 weeks of total treatment, participants received CNTX-6970 BID for an additional 6 weeks (Block 2, Period 2), completing a 24-week study period.
Posted
Mean
Standard Deviation
T score
24 Weeks
ID
Title
Description
OG000
300mg BID CNTX-6970 (DPPD): B1P1
Block 1 Period 1: Participants were instructed to take 300 mg CNTX-6970 BID for weeks 1 through 6
Secondary
Staircase-evoked Pain Assessment
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. Lower values correspond to less pain.
The NRS from the post-step was analyzed.
ITT - Intention to Treat Population
Posted
Mean
Standard Deviation
units on a scale
24 Weeks
ID
Title
Description
OG000
300mg BID CNTX-6970 (DPPD): B1P1
Block 1 Period 1: Participants were instructed to take 300 mg CNTX-6970 BID for weeks 1 through 6
OG001
Placebo BID (DPPD): B1P2
Block 1 Period 2: Participants were instructed to take matching placebo BID for weeks 6 through 12
OG002
Placebo BID (PDDP): B1P1
Block 1 Period 1: Participants were instructed to take matching placebo BID for weeks 1 through 6
Time Frame
Adverse events were collected from the time of consent through study completion or early withdrawal (24 weeks). If ongoing at the end of the study, the subject was referred for appropriate treatment.
Description
The investigator or designee was required to record all observed and reported AEs at each visit.
All AEs, serious and not serious, were recorded on the AE eCRF page using appropriate medical terminology. Severity and relationship to study drug were assessed by the investigator as described in the protocol.
(add in safety populaton)
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
300mg BID CNTX-6970 (DPPD): B1P1
Block 1 Period 1: Participants were instructed to take 300 mg CNTX-6970 BID for weeks 1 through 6
0
28
0
28
14
28
EG001
Placebo BID (PDDP): B1P1
Block 1 Period 1: Participants were instructed to take matching placebo BID for weeks 1 through 6
0
27
0
27
14
27
EG002
300 mg BID CNTX-6970 (PDDP): B1P2
Block 1 Period 2: Participants were instructed to take 300 mg CNTX-6970 BID for weeks 6 through 12
0
25
1
25
7
25
EG003
Placebo BID (DPPD): B1P2
Block 1 Period 2: Participants were instructed to take matching placebo BID for weeks 6 through 12
0
23
1
23
7
23
EG004
Placebo BID (DPPD): B2P1
Block 1 Period 1: Participants were instructed to take matching placebo BID for weeks 1 through 6
0
20
0
20
3
20
EG005
300 mg CNTX-6970 (DPPD): B2P2
Block 2 Period 2: Participants were instructed to take 300 mg CNTX-6970 BID for weeks 18 through 24
0
20
0
20
4
20
EG006
300 mg CNTX-6970 BID (PDDP): B2P1
Block 2 Period 1: Participants were instructed to take 300 mg CNTX-6970 BID for weeks 12 through 18
0
19
0
19
7
19
EG007
Placebo BID (PDDP): B2P2
Block 2 Period 2: Participants were instructed to take matching Placebo BID for weeks 18 through 24