A Phase 3 Efficacy and Safety Study of Intra-articular CN... | NCT03429049

Status Module

Label	Type	Description	Intervention Names
Placebo	Placebo Comparator	Matching placebo of 2.0 mL for IA injection	Drug: Placebo
CNTX-4975-05	Experimental	Pre-filled glass syringes administered as a single 2.0 mL IA injection	Drug: CNTX-4975-05

Name	Type	Description	Arm Group Labels	Other Names
CNTX-4975-05	Drug	Receiving CNTX-4975-05 injection	CNTX-4975-05
Placebo

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline in Average Weekly Pain With Walking (NPRS 0-10) in the Index Knee	Average daily OA pain in the index knee while walking was evaluated using a 0 to 10 Numerical Pain Rating Scale (NPRS) (0 = no pain and 10 = worst possible pain). 0 was the best score and 10 was the worst score. Subjects used an ePRO at bedtime (9:00 PM ± 3 hours) to record on a daily basis their average daily OA knee pain score with walking during the previous 24 hours.	Baseline, Week 12

Secondary Outcomes

Measure	Description	Time Frame
Mean Change From Baseline in WOMAC A (Pain) Dimension Total Score	The Western Ontario and McMaster Universities developed the Western Ontario and McMaster Universities Arthritis Index (WOMAC) score to use among patients with knee and/or hip OA. The WOMAC is a validated, multidimensional measure of pain, stiffness, and physical functional disability that is sensitive to the effects of drugs or other interventions. This study used the 11-box NPRS format ranging from 0 (none or no pain/stiffness/difficulty) to 10 (extreme). The WOMAC is a self-administered index that contains 24 items asked in relation to the index knee joint. The WOMAC has 3 dimensions: Pain (Subscale A), Stiffness (Subscale B), and Physical Function (Subscale C). Lower scores mean a better outcome and higher scores mean a worse outcome. The pain dimension includes 5 items about the amount of pain experienced doing various activities (walking, stair climbing, nocturnal, at rest, weight bearing). The score ranges from 0 to 50.

Eligibility Module

Eligibility Criteria

Key Inclusion Criteria:

Male or female subjects between 40 and 95 years of age (inclusive) at the time of the Screening Visit with the ability to comply with answering the electronic diary using the study-provided tablet computers.
Confirmation of osteoarthritis (OA) of the knee.
Confirmation of OA of the index knee.
Moderate to severe pain in the index knee associated with OA must be stable for a minimum of 6 months prior to Screening, as assessed by the investigator.
BMI ≤45 kg/m^2.
Must have failed 2 or more prior therapies.
Females not of childbearing potential, defined as post-menopausal for at least 1 year, or surgically sterile, or practicing one of the following medically acceptable methods of birth control throughout the study period.
Subject agrees to stay on their current pain medication (including over the counter (OTC) medications) from the time of Screening through Week 12. The current pain medication must be taken only for pain in the index knee, and not for another pain indication.
Subject agrees to take only the allowed rescue medications for OA knee pain of the index knee from the time of Screening through study completion and agrees to use no topical medications for OA knee pain during the trial.

Key Exclusion Criteria:

Joint replacement surgery of the index knee at any time, or open surgery of the index knee in the past 24 months.
Prior arthroscopic surgery of the index knee within 6 months of Screening.
Any painful conditions of the index knee due to joint disease other than OA.
Periarticular pain from any cause.
Pain in the non-index knee that is >3 on a numeric pain rating scale (NPRS) (0-10) when walking or at rest.
Other chronic pain anywhere in the body that requires the use of analgesic medications.
Instability of the index knee.
Misalignment (>10 degrees varus or valgus) of the index knee on standing.
Documented history of neuropathic arthropathy or finding of bony fragmentation in the index knee with imaging.
Physical/ occupational/ chiropractic therapy for the lower extremities or acupuncture for the lower extremities within 30 days of Screening, or need for such therapy during the study.
Plans to have surgery, other invasive procedures, or IA injections while participating in the study.
Has used topical capsaicin on the index knee within 90 days of Screening.
Current use of opioids for any condition other than for OA of the index knee.
Corticosteroid injection into the index knee within 90 days of Screening.
Received IA viscosupplementation (eg, Synvisc®, Hyalgan®) within 90 days of Screening.

Name	Affiliation	Role
Randall M. Stevens, MD	Centrexion Therapeutics	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
Alabama Orthopaedic Center - Research		Birmingham	Alabama	35209	United States
Cahaba Research, Inc

Results Section

Participant Flow Module

ID	Title	Description
FG000	Placebo	Matching placebo of 2.0 mL for IA injection
FG001	CNTX-4975-05	Pre-filled glass syringes administered as a single 2.0 mL IA injection

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Mar 1, 2022

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

Years

Title

Denominators

Categories

Title	Measurements
	BG00061.8± 9.5 BG00161.8± 9.1 BG00261.8± 9.2

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00083 BG001123 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG00023 BG00137 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0001 BG0010 BG002

Body Mass Index

Mean

Standard Deviation

kg/m^2

Title

Denominators

Categories

Title	Measurements
	BG00032.07± 5.801 BG00131.55± 5.692 BG002

Baseline Pain with Walking NPRS (0-10) Score

Average daily OA pain in the index knee while walking was evaluated using a 0 to 10 Numerical Pain Rating Scale (NPRS) (0 = no pain and 10 = worst possible pain). 0 was the best score and 10 was the worst score.

Mean

Standard Deviation

score on a scale

Title

Denominators

Categories

Title	Measurements
	BG0007.09± 1.152 BG001

Baseline WOMAC A (Pain) Domain Score (range 0-50)

The Western Ontario and McMaster Universities Arthritis Index (WOMAC) is a validated, multidimensional measure of pain, stiffness, and physical functional disability that is sensitive to the effects of drugs or other interventions for knee or hip OA. This study used the 11-box NPRS format ranging from 0 (none or no pain/stiffness/difficulty) to 10 (extreme).The pain dimension includes 5 items about the amount of pain experienced doing various activities (walking, stair climbing, nocturnal, at rest, weight bearing). The score ranges from 0 to 50. 0 being the best score and 50 being the worst.

Mean

Standard Deviation

score on a scale

Title

Denominators

Categories

Title	Measurements
	BG00030.80± 8.166 BG001

Baseline WOMAC B (Stiffness) Domain Score (range 0-20)

The Western Ontario and McMaster Universities Arthritis Index (WOMAC) is a validated, multidimensional measure of pain, stiffness, and physical functional disability that is sensitive to the effects of drugs or other interventions for knee or hip OA. This study used the 11-box NPRS format ranging from 0 (none or no pain/stiffness/difficulty) to 10 (extreme).The stiffness dimension includes 2 items about the joint stiffness upon wakening and joint stiffness later in the day. The score ranges from 0 to 20. 0 being the best score and 20 being the worst.

Mean

Standard Deviation

score on a scale

Title

Denominators

Categories

Title	Measurements
	BG00013.24± 3.389 BG001

Baseline WOMAC C (Function) Domain Score (range 0-170)

The Western Ontario and McMaster Universities Arthritis Index (WOMAC) is a validated, multidimensional measure of pain, stiffness, and physical functional disability that is sensitive to the effects of drugs or other interventions for knee or hip OA. This study used the 11-box NPRS format ranging from 0 (none or no pain/stiffness/difficulty) to 10 (extreme).The physical function dimension asks about the degree of difficulty in doing 17 activities due to the reference joint. The score ranges from 0 to 170. 0 being the best score and 170 being the worst.

Mean

Standard Deviation

score on a scale

Title

Denominators

Categories

Title	Measurements
	BG000105.25± 29.755 BG001

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

Change From Baseline in Average Weekly Pain With Walking (NPRS 0-10) in the Index Knee

Subjects used an ePRO at bedtime (9:00 PM ± 3 hours) to record on a daily basis their average daily OA knee pain score with walking during the previous 24 hours.

The intent to treat (ITT) population included all randomized subjects who received any amount of investigational product and all observed data.

Posted

Least Squares Mean

Standard Error

score on a scale

Baseline, Week 12

ID	Title	Description
OG000	Placebo	Matching placebo of 2.0 mL for IA injection
OG001	CNTX-4975-05	Pre-filled glass syringes administered as a single 2.0 mL IA injection

Units	Counts
Participants	OG000130 OG001177

Title

Denominators

Categories

Title	Measurements
	OG000-2.84± 0.212 OG001-3.17± 0.182

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	The NRS least squares mean difference in change from baseline between treatment arms was analyzed with a mixed model for repeated measures (MMRM). It included terms for treatment, pooled study center, baseline K L grade category for the index knee, baseline BMI category, sex, study week, treatment by visit study week interaction, and baseline average daily pain with walking NPRS (0-10) score as covariates, using an unstructured covariance structure.	Mixed Models Analysis		0.1904		Least Squares Mean Difference	-0.33	Standard Error of the Mean	0.256	2-Sided	95	-0.84	0.17					Superiority

Secondary

Mean Change From Baseline in WOMAC A (Pain) Dimension Total Score

The Western Ontario and McMaster Universities developed the Western Ontario and McMaster Universities Arthritis Index (WOMAC) score to use among patients with knee and/or hip OA. The WOMAC is a validated, multidimensional measure of pain, stiffness, and physical functional disability that is sensitive to the effects of drugs or other interventions. This study used the 11-box NPRS format ranging from 0 (none or no pain/stiffness/difficulty) to 10 (extreme).

The WOMAC is a self-administered index that contains 24 items asked in relation to the index knee joint. The WOMAC has 3 dimensions: Pain (Subscale A), Stiffness (Subscale B), and Physical Function (Subscale C). Lower scores mean a better outcome and higher scores mean a worse outcome.

The pain dimension includes 5 items about the amount of pain experienced doing various activities (walking, stair climbing, nocturnal, at rest, weight bearing). The score ranges from 0 to 50.

The intent to treat (ITT) population included all randomized subjects who received any amount of investigational product and all observed data.

Posted

Least Squares Mean

Standard Error

score on a scale

Baseline, Week 12

ID	Title	Description
OG000	Placebo	Matching placebo of 2.0 mL for IA injection
OG001	CNTX-4975-05	Pre-filled glass syringes administered as a single 2.0 mL IA injection

Secondary

Mean Change From Baseline WOMAC B (Stiffness) Dimension Total Score

The stiffness dimension has 2 items: joint stiffness upon wakening and joint stiffness later in the day. The score ranges from 0 to 20.

The intent to treat (ITT) population included all randomized subjects who received any amount of investigational product and all observed data.

Posted

Least Squares Mean

Standard Error

score on a scale

Baseline, Week 12

ID	Title	Description
OG000	Placebo	Matching placebo of 2.0 mL for IA injection
OG001	CNTX-4975-05	Pre-filled glass syringes administered as a single 2.0 mL IA injection

Secondary

Mean Change From Baseline in WOMAC C (Physical Function) Dimension Total Score

The function dimension asks about the degree of difficulty in doing 17 activities due to the reference joint. The score ranges from 0 to 170.

The intent to treat (ITT) population included all randomized subjects who received any amount of investigational product and all observed data.

Posted

Least Squares Mean

Standard Error

score on a scale

Baseline, Week 12

ID	Title	Description
OG000	Placebo	Matching placebo of 2.0 mL for IA injection
OG001	CNTX-4975-05	Pre-filled glass syringes administered as a single 2.0 mL IA injection

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Acetabulum Fracture	Injury, poisoning and procedural complications	MEDRA	Systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected189 at risk
Craniocerebral Injury	Injury, poisoning and procedural complications	MEDRA	Systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected189 at risk
Foot Fracture	Injury, poisoning and procedural complications	MEDRA	Systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected189 at risk
Hip Fracture	Injury, poisoning and procedural complications	MEDRA	Systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected189 at risk
Chest Pain	General disorders	MEDRA	Systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected189 at risk
Systemic inflammatory response	General disorders	MEDRA	Systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected189 at risk
Oestrogen receipt positive breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MEDRA	Systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected189 at risk
Prostate Cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MEDRA	Systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected189 at risk
Hypotension	Vascular disorders	MEDRA	Systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected189 at risk
Peripheral Ischaemia	Vascular disorders	MEDRA	Systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected189 at risk
Supraventricular Tachycardia	Cardiac disorders	MEDRA	Systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected189 at risk
Vertigo Positional	Ear and labyrinth disorders	MEDRA	Systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected189 at risk
Acute Respiratory Failure	Respiratory, thoracic and mediastinal disorders	MEDRA	Systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected189 at risk
Branchospasm	Respiratory, thoracic and mediastinal disorders	MEDRA	Systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected189 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MEDRA	Systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected189 at risk
Hip Arthroplasty	Surgical and medical procedures	MEDRA	Systematic Assessment	EG0001 events1 affected136 at risk EG0010 events0 affected189 at risk
Appendicitis	Infections and infestations	MEDRA	Systematic Assessment	EG0000 events0 affected136 at risk EG0011 events1 affected189 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Arthralgia	Musculoskeletal and connective tissue disorders	MEDRA	Systematic Assessment	EG0006 events6 affected136 at risk EG00119 events19 affected189 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MEDRA	Systematic Assessment	EG0003 events3 affected136 at risk EG0018 events8 affected189 at risk
Back pain	Musculoskeletal and connective tissue disorders	MEDRA	Systematic Assessment	EG0002 events2 affected136 at risk EG0015 events5 affected189 at risk
Joint effusion	Musculoskeletal and connective tissue disorders	MEDRA	Systematic Assessment	EG0001 events1 affected136 at risk EG0015 events5 affected189 at risk
Joint swelling	Musculoskeletal and connective tissue disorders	MEDRA	Systematic Assessment	EG0003 events3 affected136 at risk EG0013 events3 affected189 at risk
Joint stiffness	Musculoskeletal and connective tissue disorders	MEDRA	Systematic Assessment	EG0000 events0 affected136 at risk EG0014 events4 affected189 at risk
Upper respiratory tract infection	Infections and infestations	MEDRA	Systematic Assessment	EG0007 events7 affected136 at risk EG0018 events8 affected189 at risk
Viral upper respiratory tract infection	Infections and infestations	MEDRA	Systematic Assessment	EG0003 events3 affected136 at risk EG0014 events4 affected189 at risk
Influenza	Infections and infestations	MEDRA	Systematic Assessment	EG0001 events1 affected136 at risk EG0015 events5 affected189 at risk
Urinary tract infection	Infections and infestations	MEDRA	Systematic Assessment	EG0003 events3 affected136 at risk EG0013 events3 affected189 at risk
Nausea	Gastrointestinal disorders	MEDRA	Systematic Assessment	EG0002 events2 affected136 at risk EG00112 events12 affected189 at risk
Procedural pain	Injury, poisoning and procedural complications	MEDRA	Systematic Assessment	EG0002 events2 affected136 at risk EG0015 events5 affected189 at risk
Fall	Injury, poisoning and procedural complications	MEDRA	Systematic Assessment	EG0002 events2 affected136 at risk EG0014 events4 affected189 at risk
Dizziness	Nervous system disorders	MEDRA	Systematic Assessment	EG0003 events3 affected136 at risk EG0016 events6 affected189 at risk
Headache	Nervous system disorders	MEDRA	Systematic Assessment	EG0001 events1 affected136 at risk EG0014 events4 affected189 at risk
Injection site joint pain	General disorders	MEDRA	Systematic Assessment	EG0001 events1 affected136 at risk EG0014 events4 affected189 at risk
Hypertension	Vascular disorders	MEDRA	Systematic Assessment	EG0002 events2 affected136 at risk EG0015 events5 affected189 at risk
Hyperhidrosis	Skin and subcutaneous tissue disorders	MEDRA	Systematic Assessment	EG0000 events0 affected136 at risk EG0016 events6 affected189 at risk
Tooth extraction	Surgical and medical procedures	MEDRA	Systematic Assessment	EG0003 events3 affected136 at risk EG0010 events0 affected189 at risk

ID	Term
D001168	Arthritis
D007592	Joint Diseases
D009140	Musculoskeletal Diseases
D012216	Rheumatic Diseases
D009461	Neurologic Manifestations
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms

ID	Title	Description
BG000	Placebo	Matching placebo of 2.0 mL for IA injection
BG001	CNTX-4975-05	Pre-filled glass syringes administered as a single 2.0 mL IA injection
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Matching placebo of 2.0 mL for IA injection	0	136	6	136	45	136
EG001	CNTX-4975-05	Pre-filled glass syringes administered as a single 2.0 mL IA injection	1	189	6	189	110	189