Investigation of 1.2% Sodium Hyaluronate for Treatment of... | NCT00988091

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
IA-SA	Placebo Comparator	Each participant received a single intra-articular (IA) injection of buffered saline (SA) into the target knee, and was followed for a total of 26 weeks in the double-blind period. Participants had the option of continuing into the open-label period in which they could receive a single intra-articular injection of 1.2% sodium hyaluronate (IA-BioHA) into the target knee and be followed for an additional 26 weeks.	Device: Buffered Saline
IA-BioHA	Experimental	Each participant received a single intra-articular (IA) injection of 1.2% sodium hyaluronate (BioHA) into the target knee, and was followed for a total of 26 weeks in the double-blind period. Participants had the option of continuing into the open-label period in which they received a single intra-articular injection of 1.2% sodium hyaluronate (IA-BioHA) into the target knee and were followed for an additional 26 weeks.	Device: 1.2% Sodium Hyaluronate

Interventions

Name	Type	Description	Arm Group Labels	Other Names
1.2% Sodium Hyaluronate	Device	IA-BioHA is supplied in a disposable 7 ml nominal volume glass syringe containing 60 mg/5 ml of 1.2% sodium hyaluronate. Participants are given a single injection in the target knee on Day 1 of the double-blind period and optionally on the first day of the open-label period (approximately week 27).

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline in the Visual Analogue Score (VAS) Pain Score of the 50-foot Walk Test at Week 26	The level of pain is estimated by the participant following a walk of 50 feet in length which is observed by the investigator. Pain estimates were recorded on a 100 millimeter visual analog scale. A score of 0 millimeters means there was no pain; a score of 100 millimeters means extreme pain. Change from baseline is calculated: week 26 VAS Pain Score - Baseline VAS Pain Score.	Day 0 (baseline) through Week 26

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline in Western Ontario McMaster University Osteoarthritis Index (WOMAC) Disability Scores at Week 26	Adjusted mean of all WOMAC pain, stiffness and physical function subscores on Visual Analog Scale (VAS) of 100 mm; 0 mm = no pain, stiffness and difficulty; 100 mm = extreme pain, stiffness and difficulty. Change from baseline calculated as: Week 26 minus baseline.	Day 0 (baseline), week 26

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Chronic osteoarthritis (OA) of target knee confirmed by American College of Rheumatology (ACR) Criteria.
Pain due to OA in target knee present for at least 6 months.
During Screening and Baseline visits, subjects will require a visual analog scale (VAS) score (100 mm) of ≥ 41 mm and ≤ 90 mm, recorded immediately following a 50-foot walk, AND at Baseline, cannot have decreased >10mm (improvement) from Screening.
A bilateral standing anteroposterior (AP) X-ray confirming OA of the target knee.
Ability and willingness to use only acetaminophen as the analgesic (rescue) study medication
Ability to perform procedures required of the pain index evaluations (unassisted walking 50 feet on a flat surface and going up and down stairs).
Willingness and ability to complete efficacy and safety questionnaires and ability to read and understand study instructions.
Signed Subject Informed Consent Form

Exclusion Criteria:

Any major injury (including sports injuries) to the target knee within the prior 12 months.
Any surgery to the target knee, hip and contralateral hip within the prior 12 months.
Major and minor articular procedures
Inflammatory arthropathies such as rheumatoid arthritis, lupus arthropathy, or psoriatic arthritis.
Gout or calcium pyrophosphate (pseudogout) diseases of the target knee that have flared within the previous 6 months.
X-ray findings of acute fractures, severe loss of bone density, avascular necrosis, and/or severe bone or joint deformity in the target knee.
Osteonecrosis of either knee.
Fibromyalgia, pes anserine bursitis, lumbar radiculopathy, and/or neurogenic or vascular claudication.
Significant anterior knee pain due to diagnosed isolated patella-femoral syndrome or chondromalacia in the target knee.
Significant target knee joint infection or skin disorder/infection within the previous 6 months prior to study enrollment.
Symptomatic OA of the hips, spine, or ankle, if it would interfere with the evaluation of the target knee.
Known hypersensitivity to acetaminophen, sodium hyaluronate, or phosphate buffered saline solution.
Women of childbearing potential who are pregnant, nursing, or planning to become pregnant, and those who do not agree to remain on an acceptable method of birth control throughout the entire study period.
Recurrent medical history of severe allergic or immune-mediated reactions or other immune disorders.
Vascular insufficiency of lower limbs or peripheral neuropathy severe enough to interfere with the study evaluation.
Current treatment or treatment within the previous 2 years prior to Screening for any malignancy unless specific written permission is provided by the Sponsor (excluding basal cell or squamous cell carcinoma of the skin).
Chronic liver disease and active liver disease based on liver profile of aspartate aminotransferase (AST), alanine transaminase (ALT), and conjugated bilirubin >2 times the upper limit of normal.
Renal insufficiency based on serum creatinine >2.0 mg/dL.
Any clinically significant laboratory value based on clinical history that the Investigator feels may affect the study evaluation.
Any intercurrent chronic disease or condition that may interfere with the completion of the 6-month (or 12-month) follow-up of the study, such as liver disease, severe coronary disease, drug abuse, disordered mental state, or other clinically significant condition.
Current alcoholism, and/or any known current addiction to pain medications.
Any clinically significant finding that would place the patient at health risk, impact the study, or affect the completion of the study.
Any psychiatric illness that would prevent comprehension of the details and nature of the study.
Participation in any experimental device study within 6 months prior to the Screening, or an experimental drug study within 1 month prior to the Screening

Name	Affiliation	Role
Clinical Development Support	Ferring Pharmaceuticals	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Apex Clinical Trials, LLC		Homewood	Alabama		United States
Tucson Orthopaedic Institute

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	IA-SA	Each participant received a single intra-articular (IA) injection of buffered saline (SA) into the target knee, and was followed for a total of 26 weeks in the double-blind period. Participants had the option of continuing into the open-label period in which they could receive a single intra-articular injection of 1.2% sodium hyaluronate (IA-BioHA) into the target knee and be followed for an additional 26 weeks.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

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 the Visual Analogue Score (VAS) Pain Score of the 50-foot Walk Test at Week 26

The level of pain is estimated by the participant following a walk of 50 feet in length which is observed by the investigator. Pain estimates were recorded on a 100 millimeter visual analog scale. A score of 0 millimeters means there was no pain; a score of 100 millimeters means extreme pain. Change from baseline is calculated: week 26 VAS Pain Score - Baseline VAS Pain Score.

Intent to treat population

Posted

Least Squares Mean

Standard Error

units on a scale

Day 0 (baseline) through Week 26

ID	Title	Description
OG000	IA-SA	Each participant received a single intra-articular (IA) injection of buffered saline (SA) into the target knee, and was followed for a total of 26 weeks in the double-blind period. Participants had the option of continuing into the open-label period in which they could receive a single intra-articular injection of 1.2% sodium hyaluronate (IA-BioHA) into the target knee and be followed for an additional 26 weeks.
OG001	IA-BioHA	Each participant received a single intra-articular (IA) injection of 1.2% sodium hyaluronate (BioHA) into the target knee, and was followed for a total of 26 weeks in the double-blind period. Participants had the option of continuing into the open-label period in which they received a single intra-articular injection of 1.2% sodium hyaluronate (IA-BioHA) into the target knee and were followed for an additional 26 weeks.

Units	Counts
Participants	OG000294 OG001295

Title

Denominators

Categories

Title	Measurements
	OG000-33.48± 1.81 OG001-28.15± 1.82

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	A treatment difference of >=7.0 mm and a pooled SD of 27.6 mm, requires a sample size of 244 subjects/treatment to complete the trial at 80% power at a two-sided significance level of 5%. To account for 18% dropout rate, the sample size was increased to 298/arm (total of 596). The primary null hypothesis (Ho) is that the effect of the two treatment groups at 26 weeks is equal and the corresponding alternative hypothesis (HA) is that the effect of the two treatment groups at 26 weeks is unequal.	Mixed Models Repeated Measures ANCOVA	The analysis included baseline score as a covariate and study center as a stratification variable.	0.034	The p-value was not adjusted for multiple comparisons because there was a single treatment comparison for the primary endpoint. The a priori threshold for statistical significance was p <0.05.	Adjusted mean difference	5.33			2-Sided	95	0.41	10.24

Secondary

Change From Baseline in Western Ontario McMaster University Osteoarthritis Index (WOMAC) Disability Scores at Week 26

Adjusted mean of all WOMAC pain, stiffness and physical function subscores on Visual Analog Scale (VAS) of 100 mm; 0 mm = no pain, stiffness and difficulty; 100 mm = extreme pain, stiffness and difficulty. Change from baseline calculated as: Week 26 minus baseline.

Intent to treat population

Posted

Least Squares Mean

Standard Error

units on a scale

Day 0 (baseline), week 26

ID	Title	Description
OG000	IA-SA	Each participant received a single intra-articular (IA) injection of buffered saline (SA) into the target knee, and was followed for a total of 26 weeks in the double-blind period. Participants had the option of continuing into the open-label period in which they could receive a single intra-articular injection of 1.2% sodium hyaluronate (IA-BioHA) into the target knee and be followed for an additional 26 weeks.
OG001	IA-BioHA	Each participant received a single intra-articular (IA) injection of 1.2% sodium hyaluronate (BioHA) into the target knee, and was followed for a total of 26 weeks in the double-blind period. Participants had the option of continuing into the open-label period in which they received a single intra-articular injection of 1.2% sodium hyaluronate (IA-BioHA) into the target knee and were followed for an additional 26 weeks.

Secondary

Percentage of Participants With a >=20mm Improvement Between Baseline and Week 26 on the 50 Foot Walk Visual Analogue Scale (VAS) Pain Score.

Intent to treat population

Posted

Number

percentage of participants

Day 0 (baseline), Week 26

ID	Title	Description
OG000	IA-SA	Each participant received a single intra-articular (IA) injection of buffered saline (SA) into the target knee, and was followed for a total of 26 weeks in the double-blind period. Participants had the option of continuing into the open-label period in which they could receive a single intra-articular injection of 1.2% sodium hyaluronate (IA-BioHA) into the target knee and be followed for an additional 26 weeks.
OG001	IA-BioHA	Each participant received a single intra-articular (IA) injection of 1.2% sodium hyaluronate (BioHA) into the target knee, and was followed for a total of 26 weeks in the double-blind period. Participants had the option of continuing into the open-label period in which they received a single intra-articular injection of 1.2% sodium hyaluronate (IA-BioHA) into the target knee and were followed for an additional 26 weeks.

Secondary

Subjective Patient Assessment of Treatment at Week 26

At the end of the double-blind period (week 26), participants were asked: "Are you satisfied with the results of the injection?" Answers could be: 1=dissatisfied; 2=slightly satisfied; 3=satisfied; or 4=very satisfied.

Intent to treat population

Posted

Mean

Standard Deviation

units on a scale

Week 26

ID	Title	Description
OG000	IA-SA	Each participant received a single intra-articular (IA) injection of buffered saline (SA) into the target knee, and was followed for a total of 26 weeks in the double-blind period. Participants had the option of continuing into the open-label period in which they could receive a single intra-articular injection of 1.2% sodium hyaluronate (IA-BioHA) into the target knee and be followed for an additional 26 weeks.
OG001	IA-BioHA	Each participant received a single intra-articular (IA) injection of 1.2% sodium hyaluronate (BioHA) into the target knee, and was followed for a total of 26 weeks in the double-blind period. Participants had the option of continuing into the open-label period in which they received a single intra-articular injection of 1.2% sodium hyaluronate (IA-BioHA) into the target knee and were followed for an additional 26 weeks.

Secondary

Number of Tablets of Rescue Medication Used Between Visits

Acetaminophen (500-mg tablets) was provided to study participants as a rescue medication in case they needed a pain medication during the study. The mean number of tablets of rescue medication should have been summarized, however the data was not captured in a reliable way and is therefore not reported.

Posted

Mean

Standard Deviation

tablets

Day 1 to week 26

ID	Title	Description
OG000	IA-SA	Each participant received a single intra-articular (IA) injection of buffered saline (SA) into the target knee, and was followed for a total of 26 weeks in the double-blind period. Participants had the option of continuing into the open-label period in which they could receive a single intra-articular injection of 1.2% sodium hyaluronate (IA-BioHA) into the target knee and be followed for an additional 26 weeks.
OG001	IA-BioHA	Each participant received a single intra-articular (IA) injection of 1.2% sodium hyaluronate (BioHA) into the target knee, and was followed for a total of 26 weeks in the double-blind period. Participants had the option of continuing into the open-label period in which they received a single intra-articular injection of 1.2% sodium hyaluronate (IA-BioHA) into the target knee and were followed for an additional 26 weeks.

Secondary

Change From Baseline in Patient Global Assessment at Week 26

Participants were asked to mark along a 100mm visual analog scale (VAS) indicating the point best representing the severity of the knee pain that day. The left side of the VAS was 0=no pain and the right side was 100 = extreme pain. Change from baseline was calculated as Week 26 - Baseline.

Intent to treat population

Posted

Least Squares Mean

Standard Error

units on a scale

Day 0 (baseline), Week 26

ID	Title	Description
OG000	IA-SA	Each participant received a single intra-articular (IA) injection of buffered saline (SA) into the target knee, and was followed for a total of 26 weeks in the double-blind period. Participants had the option of continuing into the open-label period in which they could receive a single intra-articular injection of 1.2% sodium hyaluronate (IA-BioHA) into the target knee and be followed for an additional 26 weeks.
OG001	IA-BioHA	Each participant received a single intra-articular (IA) injection of 1.2% sodium hyaluronate (BioHA) into the target knee, and was followed for a total of 26 weeks in the double-blind period. Participants had the option of continuing into the open-label period in which they received a single intra-articular injection of 1.2% sodium hyaluronate (IA-BioHA) into the target knee and were followed for an additional 26 weeks.

Secondary

Percentage of Observed Osteoarthritis Research Society International (OARSI30) Responders Using the Visual Analogue Scale (VAS) to Assess Pain Following a 50-foot Walk at Week 26

Responders are identified based on a calculation of three scales: 50-foot walk test for pain, function (WOMAC Disability score) and global assessment (Patient Global Assessment Score) scales. Each of the individual scales was completed by the participant. A responder showed considerable improvement in pain or function (>=50 percent and absolute change of >=20 millimeters), or improvement in at least two of three categories: Pain and/or Function and/or Patient Global Assessment scales of >=20 percent and absolute change >=10 millimeter. Response at Week 26 is compared to baseline.

Intent to treat population

Posted

Number

percentage of participants

Day 0 (baseline), week 26

ID	Title	Description
OG000	IA-SA	Each participant received a single intra-articular (IA) injection of buffered saline (SA) into the target knee, and was followed for a total of 26 weeks in the double-blind period. Participants had the option of continuing into the open-label period in which they could receive a single intra-articular injection of 1.2% sodium hyaluronate (IA-BioHA) into the target knee and be followed for an additional 26 weeks.
OG001	IA-BioHA	Each participant received a single intra-articular (IA) injection of 1.2% sodium hyaluronate (BioHA) into the target knee, and was followed for a total of 26 weeks in the double-blind period. Participants had the option of continuing into the open-label period in which they received a single intra-articular injection of 1.2% sodium hyaluronate (IA-BioHA) into the target knee and were followed for an additional 26 weeks.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Bradycardia	Cardiac disorders	MedDRA (12.0)	Systematic Assessment	EG0000 affected298 at risk EG0011 affected298 at risk EG0020 affected454 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA (12.0)	Systematic Assessment	EG0000 affected298 at risk EG0011 affected298 at risk EG0020 affected454 at risk
Myopericarditis	Cardiac disorders	MedDRA (12.0)	Systematic Assessment	EG0000 affected298 at risk EG0011 affected298 at risk EG0020 affected454 at risk
Angina pectoris	Cardiac disorders	MedDRA (12.0)	Systematic Assessment	EG0001 affected298 at risk EG0010 affected298 at risk EG0021 affected454 at risk
Atrial fibrillation	Cardiac disorders	MedDRA (12.0)	Systematic Assessment	EG0002 affected298 at risk EG0010 affected298 at risk EG0020 affected454 at risk
Myocardial infarction	Cardiac disorders	MedDRA (12.0)	Systematic Assessment	EG0000 affected298 at risk EG0010 affected298 at risk EG0021 affected454 at risk
Urethral intrinsic sphincter deficiency	Congenital, familial and genetic disorders	MedDRA (12.0)	Systematic Assessment	EG0000 affected298 at risk EG0011 affected298 at risk EG0020 affected454 at risk
Chest pain	General disorders	MedDRA (12.0)	Systematic Assessment	EG0000 affected298 at risk EG0011 affected298 at risk EG0020 affected454 at risk
Death	General disorders	MedDRA (12.0)	Systematic Assessment	EG0000 affected298 at risk EG0011 affected298 at risk EG0020 affected454 at risk
Intraspinal abscess	Infections and infestations	MedDRA (12.0)	Systematic Assessment	EG0000 affected298 at risk EG0011 affected298 at risk EG0020 affected454 at risk
Pneumonia	Infections and infestations	MedDRA (12.0)	Systematic Assessment	EG0000 affected298 at risk EG0011 affected298 at risk EG0021 affected454 at risk
Diverticulitis	Infections and infestations	MedDRA (12.0)	Systematic Assessment	EG0000 affected298 at risk EG0010 affected298 at risk EG0021 affected454 at risk
Urosepsis	Infections and infestations	MedDRA (12.0)	Systematic Assessment	EG0000 affected298 at risk EG0010 affected298 at risk EG0021 affected454 at risk
Femur fracture	Injury, poisoning and procedural complications	MedDRA (12.0)	Systematic Assessment	EG0000 affected298 at risk EG0011 affected298 at risk EG0020 affected454 at risk
Upper limb fracture	Injury, poisoning and procedural complications	MedDRA (12.0)	Systematic Assessment	EG0001 affected298 at risk EG0010 affected298 at risk EG0020 affected454 at risk
Joint injury	Injury, poisoning and procedural complications	MedDRA (12.0)	Systematic Assessment	EG0000 affected298 at risk EG0010 affected298 at risk EG0021 affected454 at risk
Heart rate irregular	Investigations	MedDRA (12.0)	Systematic Assessment	EG0001 affected298 at risk EG0010 affected298 at risk EG0020 affected454 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (12.0)	Systematic Assessment	EG0000 affected298 at risk EG0011 affected298 at risk EG0021 affected454 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA (12.0)	Systematic Assessment	EG0000 affected298 at risk EG0011 affected298 at risk EG0020 affected454 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (12.0)	Systematic Assessment	EG0001 affected298 at risk EG0010 affected298 at risk EG0020 affected454 at risk
Uterine leiomyoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (12.0)	Systematic Assessment	EG0001 affected298 at risk EG0010 affected298 at risk EG0020 affected454 at risk
Headache	Nervous system disorders	MedDRA (12.0)	Systematic Assessment	EG0000 affected298 at risk EG0011 affected298 at risk EG0020 affected454 at risk
Syncope	Nervous system disorders	MedDRA (12.0)	Systematic Assessment	EG0001 affected298 at risk EG0010 affected298 at risk EG0020 affected454 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA (12.0)	Systematic Assessment	EG0000 affected298 at risk EG0010 affected298 at risk EG0021 affected454 at risk
Urinary incontinence	Renal and urinary disorders	MedDRA (12.0)	Systematic Assessment	EG0000 affected298 at risk EG0011 affected298 at risk EG0020 affected454 at risk
Renal failure acute	Renal and urinary disorders	MedDRA (12.0)	Systematic Assessment	EG0000 affected298 at risk EG0010 affected298 at risk EG0021 affected454 at risk
Pelvic prolapse	Reproductive system and breast disorders	MedDRA (12.0)	Systematic Assessment	EG0000 affected298 at risk EG0011 affected298 at risk EG0020 affected454 at risk
Nephrectomy	Surgical and medical procedures	MedDRA (12.0)	Systematic Assessment	EG0000 affected298 at risk EG0011 affected298 at risk EG0020 affected454 at risk
Spinal fusion surgery	Surgical and medical procedures	MedDRA (12.0)	Systematic Assessment	EG0000 affected298 at risk EG0011 affected298 at risk EG0020 affected454 at risk
Knee arthroplasty	Surgical and medical procedures	MedDRA (12.0)	Systematic Assessment	EG0000 affected298 at risk EG0010 affected298 at risk EG0021 affected454 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA (12.0)	Systematic Assessment	EG0000 affected298 at risk EG0010 affected298 at risk EG0021 affected454 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA (12.0)	Systematic Assessment	EG0000 affected298 at risk EG0010 affected298 at risk EG0021 affected454 at risk
Obesity	Metabolism and nutrition disorders	MedDRA (12.0)	Systematic Assessment	EG0000 affected298 at risk EG0010 affected298 at risk EG0021 affected454 at risk
Psychotic disorder	Psychiatric disorders	MedDRA (12.0)	Systematic Assessment	EG0000 affected298 at risk EG0010 affected298 at risk EG0021 affected454 at risk

ID	Term
D010003	Osteoarthritis
D001168	Arthritis
D007592	Joint Diseases
D009140	Musculoskeletal Diseases
D012216	Rheumatic Diseases

ID	Title	Description
BG000	IA-SA	Each participant received a single intra-articular (IA) injection of buffered saline (SA) into the target knee, and was followed for a total of 26 weeks in the double-blind period. Participants had the option of continuing into the open-label period in which they could receive a single intra-articular injection of 1.2% sodium hyaluronate (IA-BioHA) into the target knee and be followed for an additional 26 weeks.
BG001	IA-BioHA	Each participant received a single intra-articular (IA) injection of 1.2% sodium hyaluronate (BioHA) into the target knee, and was followed for a total of 26 weeks in the double-blind period. Participants had the option of continuing into the open-label period in which they received a single intra-articular injection of 1.2% sodium hyaluronate (IA-BioHA) into the target knee and were followed for an additional 26 weeks.
BG002	Total	Total of all reporting groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	IA-SA: Double-blind Period	Each participant received a single intra-articular (IA) injection of buffered saline (SA) into the target knee, and was followed for a total of 26 weeks in the double-blind period.	6	298	25	298
EG001	IA-BioHA: Double-blind Period	Each participant received a single intra-articular (IA) injection of 1.2% sodium hyaluronate (BioHA) into the target knee, and was followed for a total of 26 weeks in the double-blind period.	13	298	29	298
EG002	IA-BioHA: Open-label Period	Participants had the option of continuing into the open-label period in which their target knee received a single intra-articular (IA) injection of 1.2% sodium hyaluronate (BioHA) and they were followed for an additional 26 weeks.	12	454	32	454