Clinical Studies

The safety and effectiveness of SYNVISC (hylan g-f 20) were studied in patients ≥ 40 years old in the three concurrently controlled clinical trials. The three studies investigated a total of 136 women and 81 men. The demographics of trial participants were comparable across treatment groups with regard to age, gender and duration of osteoarthritis, except that there was a significantly greater (p = 0.04) number of men in the SYNVISC (hylan g-f 20) group and women in the control group in one study (see Table 1).

One study was a multicenter study conducted at four sites in Germany. This was a randomized, double-blind prospective clinical trial with two treatment groups. The study compared the safety and effectiveness of three weekly intra-articular injections of SYNVISC (hylan g-f 20) and of physiological saline in 103 subjects (109 knees) with osteoarthritis of the knee over a 26-week period. A significantly greater number of saline-treated patients took concurrent osteoarthritis medications than did patients treated with SYNVISC (hylan g-f 20) (see Table 2). While both the SYNVISC (hylan g-f 20) and the saline-treated groups improved significantly as compared to baseline in all effectiveness measures, the SYNVISC (hylan g-f 20) group showed a significantly greater improvement in all outcome measures than did the saline-treated patients over a 26-week period (see Tables 3A and 3B).

A second study conducted at a single center in Germany was a concurrently controlled, randomized, double-blind prospective clinical trial with two treatment groups. This study compared the safety and effectiveness over a 26-week period of three weekly intra-articular injections of SYNVISC (hylan g-f 20) and of physiological saline in 29 subjects (29 knees) with osteoarthritis of the knee. The results of the study were similar to those in the German multicenter study, except that the significance levels in most comparisons were smaller (see Tables 3A and 3B). In both of these studies the most pain relief and the greatest amount of treatment success occurred 8 to 12 weeks after SYNVISC (hylan g-f 20) treatment began.

Investigators obtained data at 26 weeks by telephone interviews. A validation study suggested that the results obtained in telephone interviews are equivalent to those obtained in office visits. Since investigators did not follow patients beyond week 26, the duration of pain relief beyond 26 weeks is not known. A third study was a prospective, concurrently controlled, randomized, double-blind multicenter study conducted in 90 subjects (103 knees) at five U.S. sites. The study compared the safety and effectiveness of three weekly intra-articular injections of SYNVISC (hylan g-f 20) and of three weekly arthrocenteses in subjects with osteoarthritis of the knee over a four-week period after the first injection or arthrocentesis.

Both the SYNVISC (hylan g-f 20) -treated and the arthrocentesis-treated groups improved significantly as compared to baseline in all effectiveness measures. However, there were no significant differences between the SYNVISC (hylan g-f 20) -treated and arthrocentesis-treated patients at any time during the four-week evaluation period (see Tables 3A and 3B).

Covariate analyses with the covariates of center, presence or absence of previous treatments, baseline levels of outcome measures, age, gender, body mass, effusion, baseline X-ray score, duration of osteoarthritis, treatment of contralateral knee, and presence or absence of concurrent therapies, did not reveal any factors that significantly affected the results of any of the three studies.

The German studies and the U.S. study differed in several respects, including inclusion of patients with effusions, length of no treatment period prior to SYNVISC (hylan g-f 20) injection, nature of control treatment, final evaluation time, mean duration of disease, mean weight, prior treatments for OA, pain and X-ray inclusion criteria. Thus, the German and the U.S. studies, which gave different results, investigated different patient populations and compared SYNVISC (hylan g-f 20) with different control treatments.

Although success criteria for safety were not specified in any of the three studies, adverse events were enumerated in each study. These events are included in the “Adverse Events” section.

Detailed Device Description

SYNVISC (hylan g-f 20) contains hylan A (average molecular weight 6,000,000) and hylan B hydrated gel in a buffered physiological sodium chloride solution, pH 7.2. SYNVISC (hylan g-f 20) has an elasticity (storage modulus G') at 2.5 Hz of 111 ± 13 Pascals (Pa) and a viscosity (loss modulus G”) of 25 ± 2 Pa (elasticity and viscosity of knee synovial fluid of 18 to 27- year-old humans measured with a comparable method at 2.5 Hz: G' = 117 ± 13 Pa; G” = 45 ± 8 Pa.) Each 2.25 mL syringe of SYNVISC (hylan g-f 20) contains:

• Hylan polymers (hylan A + hylan B) 16 mg
• Sodium chloride 17 mg
• Disodium hydrogen phosphate 0.32 mg
• Sodium dihydrogen phosphate monohydrate 0.08 mg
• Water for injection q.s. to 2.0 mL

TABLE 1 : DEMOGRAPHIC DATA¹

TABLE 3A : EFFECTIVENESS OF WEIGHT-BEARING PAIN¹ EVALUATED BY PATIENTS

TABLE 2 : CONCURRENT OSTEOARTHRITIS THERAPIES¹

TABLE 3B : EFFECTIVENESS OF NIGHT PAIN¹ EVALUATED BY PATIENTS

Last reviewed on RxList: 7/22/2010
This monograph has been modified to include the generic and brand name in many instances.