Primary osteoarthritis MedDRA version: 17.1 Level: LLT Classification code 10023476 Term: Knee osteoarthritis System Organ Class: 100000004859
Conditions
Interventions
Product Name: Sprifermin 100 mcg
Product Code: AS902330 100 mcg
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: Sprifermin
Current Sponsor code: AS902330
Concen
Sponsors
Merck KGaA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: The trial will enroll adult subjects of either sex with primary femorotibial osteoarthritis according to American College of Rheumatology (ACR) clinical and radiographic criteria who have Kellgren-Lawrence grades of 2 or 3 and a minimum joint space width (JSW) of = 2.5 mm in the medial compartment. Subjects must have pain in the target knee on most days and/or require symptomatic treatment of knee pain with paracetamol (acetaminophen), systemic non-steroidal anti-inflammatory drugs (NSAIDs) including COX-2 selective inhibitor (coxibs), or tramadol on most days of the previous month, and must have both: * A history of pain due to OA in the target knee for at least 6 months, and * Pain score for the target knee of 4 to 9 points in response to Question 1 of the WOMAC pain index(“how much pain have you had [in the target knee, over the past 48 hours] when walking on a flat surface?”) at screening and baseline, after washout of at least 5-half-lives of analgesic medication(s): acetaminophen, topical or oral systemic NSAIDS, coxibs, opioids, and/or tramadol. Women of childbearing potential must use a form of contraception with a failure rate of less than 1% per year throughout the trial. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 545 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 275
Exclusion criteria
Exclusion criteria: Main exclusion criteria are malalignment of > 5 degrees in the femorotibial axis of the target knee, clinical signs of inflammation (i.e., redness) in the target knee, i.a. administration of corticosteroids or hyaluronic acid into either knee within 6 months before screening, any plan for knee surgery (affecting either the target or the contralateral knee) within the next two years, concomitant conditions or treatments deemed to be incompatible with trial participation, contraindications to MRI scanning (including inability to fit in the scanner or knee coil), pregnancy or breastfeeding, participation in another clinical trial within the past 30 days, and legal incapacity or limited legal capacity.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate structural changes in cartilage thickness in the total femorotibial joint of the target knee in terms of imaging by magnetic resonance imaging (MRI);Secondary Objective: * To evaluate different dose regimens of sprifermin * To evaluate changes in symptoms of osteoarthritis (OA) * To evaluate changes in structure in terms of imaging by X-ray * To evaluate other changes in cartilage morphology in terms of imaging by MRI (sub-regions) * To evaluate changes in physical functioning * To evaluate the safety of sprifermin * To evaluate the pharmacokinetics (PK) of sprifermin in serum and in synovial fluid following i.a. injection;Primary end point(s): Change from baseline in cartilage thickness in the total femorotibial joint as evaluated by MRI at 2 years;Timepoint(s) of evaluation of this end point: at 2 years | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary efficacy endpoints are: * Changes from baseline in the WOMAC total score and in the WOMAC pain, function, and stiffness index scores over 2 years * Change from baseline in the 20-meter walk test over 2 years * Change from baseline in the PGA over 2 years * Change from baseline in minimal joint space width in the medial and lateral compartments as evaluated by X-ray over 2 years * Change from baseline in cartilage thickness in the medial and lateral compartments as well as in the total femorotibial joint over 2 years * Change from baseline in cartilage volume in the medial and lateral compartments as well as in the total femorotibial joint over 2 years * Synovial fluid levels of sprifermin/FGF-18 * Serum levels of sprifermin/FGF-18 Safety endpoints are: * Nature, incidence and severity of local and systemic AEs * Incidence of acute inflammatory reactions (AIRs), defined as increase of pain by 30 mm on a 100 mm visual analogue scale (VAS) and a self-reported synovial fluid effusion (i.e., joint swelling) within 3 days following i.a. injection * Changes in laboratory safety parameters, vital signs, 12-lead electrocardiogram (ECG) parameters, weight, and physical examinations * Incidence of surgical interventions in the target knee (including any surgical revision, cartilage removal, or any other type of surgical intervention). * Occurrence of binding and neutralizing antibodies to sprifermin/FGF-18;Timepoint(s) of evaluation of this end point: DBPC phase: * Changes from baseline in the WOMAC total score and in the WOMAC pain, function, and stiffness: over 2 years * Change from baseline in the 20-meter walk test: over 2 years * Change from baseline in the PGA: over 2 years * Change from baseline in minimal joint space width in the medial and lateral compartments as by X-ray: over 2 years * Change from baseline in cartilage thickness in the medial and lateral compartments: over 2 years * Change from baseline in cartilage volume in the m | — |
Countries
Argentina, Czech Republic, Denmark, Estonia, Hong Kong, Poland, Romania, United States
Contacts
Public ContactCommunication Centre Merck KGaA
Merck KGaA
Outcome results
None listed