Clinical Trial Results:
A multicentre study to assess the safety and efficacy of sodium hyaluronate (Hyalgan-F) produced by fermentation in knee psteoarthritis.
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Summary
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EudraCT number |
2005-002735-27 |
Trial protocol |
LV |
Global end of trial date |
13 Jun 2006
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Results information
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Results version number |
v1 |
This version publication date |
02 Apr 2022
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First version publication date |
02 Apr 2022
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Other versions |
v2 |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
R30-05-01
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Fidia Farmaceutici S.p.A
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Sponsor organisation address |
Via Ponte della Fabbrica 3/A, Abano Terme, Italy, 35031
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Public contact |
Evita Zvaigzne, ICON Clinical Research Latvia, +371 7804000, zvaigznee@iconlat.com
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Scientific contact |
Evita Zvaigzne, ICON Clinical Research Latvia, +371 7804000, zvaigznee@iconlat.com
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Sponsor organisation name |
Fidia Farmaceutici S.p.A
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Sponsor organisation address |
Via Ponte della Fabbrica 3/A, Abano Terme, Italy, 35031
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Public contact |
Lucia Beinat, Fidia Farmaceutici S.p.A, +39 049 8232512, lbeinat@fidiapharma.it
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Scientific contact |
Lucia Beinat, Fidia Farmaceutici S.p.A, +39 049 8232512, lbeinat@fidiapharma.it
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
13 Jun 2006
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
13 Jun 2006
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To evaluate the potential immunogenicity of Hyalgan-F (HA-F) a sodium hyaluronate obtained by fermentation and administered by intra-articular (i.a.) route (5 i.a., once a wek for 5 weeks) in a patients with knee osteoarthritis (OA).
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Protection of trial subjects |
Females of child-bearing potential (i.e. not in menopausal status from at least one year or permanently sterilized) had to have a negative urine pregnancy test prior to the first investigational medicinal product (IMP) administration
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
29 Sep 2005
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Safety, Efficacy, Scientific research | ||
Long term follow-up duration |
5 Months | ||
Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Latvia: 120
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Worldwide total number of subjects |
120
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EEA total number of subjects |
120
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
120
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||||||
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Pre-assignment
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Screening details |
• Patients of both genders, ambulant, aged ≥ 40 years, with primary knee OA associated with moderate to severe knee pain. • Diagnosis of OA of the knee according to ACRC. • OA of KL grade II – III • At baseline VAS pain score ≥ 40 mm • Analgesic/NSAID therapy was discontinued if previously taken prior to baseline | ||||||||||||||
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Pre-assignment period milestones
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Number of subjects started |
120 | ||||||||||||||
Number of subjects completed |
120 | ||||||||||||||
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Period 1
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Period 1 title |
overall trial (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||
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Arms
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Arm title
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Hyalgan-F (HA-F) | ||||||||||||||
Arm description |
Patients were treated with five i.a. injections of HA-F 2 ml, one injection a week for five weeks, starting from baseline [week 0]) up to six months of follow-up with clinical visits and evaluations. | ||||||||||||||
Arm type |
One arm | ||||||||||||||
Investigational medicinal product name |
Hyalgan-F
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion in pre-filled syringe
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Routes of administration |
Intraarticular use
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Dosage and administration details |
Hyalgan-F 20mg/2ml
Sodium Hyaluronate 20 mg
Sodium chloride 17 mg
Monobasic sodium phosphate 0.1 mg
Dibasic sodium phosphate 1.2 mg
Water for injection q.s. to 2 ml
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Baseline characteristics reporting groups
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Reporting group title |
overall trial
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Hyalgan-F (HA-F)
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Reporting group description |
Patients were treated with five i.a. injections of HA-F 2 ml, one injection a week for five weeks, starting from baseline [week 0]) up to six months of follow-up with clinical visits and evaluations. | ||
Subject analysis set title |
mITT 35 days
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Subject analysis set type |
Modified intention-to-treat | ||
Subject analysis set description |
The Modified Intention to Treat population (ITT) was defined as all patients who received at least one dose of the study drug with at least one post-treatment immunological data, and was used for all the immunological and efficacy analyses.
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Subject analysis set title |
mITT 60 days
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Subject analysis set type |
Modified intention-to-treat | ||
Subject analysis set description |
The Modified Intention to Treat population (ITT) was defined as all patients who received at least one dose of the study drug with at least one post-treatment immunological data, and was used for all the immunological and efficacy analyses.
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End point title |
Immunogenic response of HA-F | ||||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
The incidence of positive immunogenic response to HA-F calculated at 35 days and 60 days after treatment among patients with a negative immunogenic response at baseline
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Statistical analysis title |
Statistical Analysis | ||||||||||||||||
Comparison groups |
Hyalgan-F (HA-F) v mITT 60 days v mITT 35 days
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Number of subjects included in analysis |
353
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||||||
P-value |
= 0.05 | ||||||||||||||||
Method |
Chi-squared | ||||||||||||||||
Confidence interval |
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95% | ||||||||||||||||
sides |
1-sided
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lower limit |
- | ||||||||||||||||
upper limit |
- | ||||||||||||||||
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End point title |
Patient evaluation of knee pain after 50 ft walk (0-100 mm VAS scale) | ||||||||
End point description |
Results were summarized descriptively for each visit (Day 0, Day 35, Day 60, Day 120, and Day 180). The change from baseline was analyzed and the corresponding 95% CIs were presented. P-values were obtained from a two-sided test of the null-hypothesis that the change from baseline was zero. The time taken to perform the 50 ft walking test was also reported.
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End point type |
Secondary
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End point timeframe |
The VAS was evaluated at baseline, Day 35, Day 60, Day 120 and Day 180.
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| No statistical analyses for this end point | |||||||||
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End point title |
Immunological Parameters | ||||
End point description |
At baseline and at Day 35 (one week after the fifth i.a. injection) and Day 60 (one month after fifth i.a. injection) other blood samples of the patients were collected for:
• C3 and C4 quantification
• CH50
• AH50 determination
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End point type |
Secondary
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End point timeframe |
At baseline, Day 35 and Day 60
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| No statistical analyses for this end point | |||||
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End point title |
WOMAC index assessment. | |||
End point description |
Results were summarized descriptively for each visit (Day 0, Day 35, Day 60, Day 120, and Day 180). The change from baseline was analyzed and the corresponding 95% CIs were presented. P-values were obtained from a two-sided test of the null-hypothesis that the change from baseline was zero. The time taken to perform the 50 ft walking test was also reported.
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End point type |
Secondary
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End point timeframe |
The WOMAC was measured at baseline, Day 35, Day 60, Day 120, and Day 180.
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| No statistical analyses for this end point | ||||
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End point title |
Patient’s global assessment | |||
End point description |
. Both patients and investigators were asked to assess the overall condition of the patient (using the Global Assessment) and to judge the overall effectiveness of the study medication.
Patients’ and investigators’ global assessments, evaluated from Day 35 to Day 180
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End point type |
Secondary
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End point timeframe |
Patients’ and investigators’ global assessments, evaluated at baseline, Day 35, Day 60, Day 120, and day 180.
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| No statistical analyses for this end point | ||||
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End point title |
Patients’ and Investigators’ Overall Effectiveness Judgments | |||
End point description |
Patients’ and investigators’ overall effectiveness judgments, evaluated after Day 35 for the modified ITT population, using five different response categories
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End point type |
Secondary
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End point timeframe |
Patients’ and Investigators’ Overall Effectiveness Judgments were evaluated at baseline, Day 35, Day 60, Day 120, and Day 180.
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| No statistical analyses for this end point | ||||
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Adverse events information
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Timeframe for reporting adverse events |
The time period for recording AE was from Baseline V2 Day 0 to V10 Day 180
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
8.2
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Reporting groups
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Reporting group title |
Hyalgan-F
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 1% | |||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
