Patients with painful knee osteoarthritis MedDRA version: 21.1 Level: LLT Classification code 10029877 Term: OA knee System Organ Class: 100000004859
Conditions
Interventions
Product Name: Clodronato
Product Code: [TFR22014]
Pharmaceutical Form: Solution for injection
INN or Proposed INN: ACIDO CLODRONICO SALE DISODICO TETRAIDRATO
CAS Number: 88416-50-6
Current Sponsor cod
Sponsors
SPA-SOCIETÀ PRODOTTI ANTIBIOTICI S.P.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Female and male patients aged 50 up to 75 years at the signature of informed consent form (ICF). • Diagnosis of knee OA according to the American College of Rheumatology, confirmed by Rx during the screening (a Rx performed in the last three (3) months before Screening Visit is accepted). • Kellgren-Lawrence radiographic score between 2 and 3 degrees in the tibio-femoral joint. • Symptomatic knee OA (pain) since at least 6 months with a knee pain (VAS) ranging between 40 and 80 mm (at Screening the figure should be confirmed at the Baseline). • Female patients of childbearing potential must have a negative urine pregnan-cy test before receiving the first dose of study medication and they must com-ply with contraception methods as requested by the study protocol. • A signed ICF by the patient after exhaustive study discussion with the investigators. 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 150 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 146
Exclusion criteria
Exclusion criteria: • BMI > 35 kg/m2 (Class II obesity). • Joint instability due to other reasons than knee OA, such as f.i. algo dystrophic syndrome, either partial or complete rupture of internal / externals ligaments, kneecap instability, etc. • Otherwise located lower limb pain, such as hip pain. • Other musculoskeletal disorders related to the target knee. • Any treatment with IA drugs in the last three (3) month before Day 0- Baseline (including any formulation of corticosteroids, or hyaluronic acid injections). • Corticosteroid use by any systemic route, and hyaluronic acid injections or in-tra-articular corticosteroids for any other joint in the previous month will be not permitted. • Any treatment with systemic non-steroidal anti-inflammatory drugs (NSAIDs) in the week before Baseline, or any steroid anti-inflammatory drugs and chon-droprotective drugs in the thirty (30) days before Base¬line. • Any treatment with systemic bisphosphonates in the last twelve (12) months before Baseline. • Any treatment with glucosamine or chondroitin sulfate, diacerein and matrix metalloproteinase (MMP) inhibitors in the 4 weeks before Base¬line. • Any treatment with denosumab in the 12 months before Baseline. • Any treatment with paracetamol in the twelve (12) hours before Base¬line. • Any knee surgery in the past or knee arthroplasty. • Any diagnostic or surgical arthroscopy of the knee in the six (6) months before Baseline. • Any jaw osteonecrosis in the last twenty-four (24) months before Base¬line or at a risk of jaw osteonecrosis. • Any known hypersensitivity to the drug in the study and to its excipients or other bisphosphonates, and any hypersensitivity to paracetamol (rescue drug). • Any participation in a clinical study in which the last administration of the investigational medicinal product was within two (2) weeks before consenting to study participation (i.e. signing ICF). • Inadequate organ function defined by the following laboratory parameters: o Absolute Neutrophil Count (ANC) 1.5 x ULN or eGFR 1.5 x ULN o Serum Total Bilirubin > 1.5 x ULN • Pregnant or breastfeeding women, or women planning to become pregnant during the study. • Any positive or suspected history of alcoholism or drug use. • Clinically significant (i.e.) gastrointestinal, renal, hepatic, pulmonary, cardiovascular or neurological disease that could interfere with the outcome of the study or the patient’s ability to comply with study requirements. • Patients unwilling or unable to comply with the protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objectives of Phase II are: • to assess the safety and tolerability of different escalating doses of intra-articular (IA) clodronate in terms of serious adverse events (SAEs), adverse events (AEs), and ab-normal laboratory or any clinical signs of intolerance. • to set the defined therapeutic dose (DTD) to be used in Phase III, as the lowest clodro-nate dose leading to a ¿ 10 mm reduction in the Visual Analogue Scale (VAS) of knee pain at Week 7 vs. Placebo. The primary objectives of Phase III are: • to assess the therapeutic efficacy of DTD in patients with knee osteoarthritis (OA) based on VAS score of knee pain at Week 7 vs. Placebo. • to assess the safety and tolerability of DTD in patients with knee OA in terms of SAEs, AEs, and abnormal laboratory or any clinical signs of intolerance.;Secondary Objective: The secondary objectives of Phase II are: • to assess the VAS knee pain at each visit • to describe the effects of different escalating doses of IA clodronate on knee function by means of Lequesne Algofunctional Index and Western Scale Ontario MacMaster (WOMAC) • to assess the knee range of motion by means of knee extension and knee flexion • to measure the use of rescue drug consumption (paracetamol) in patients treated with different escalating doses of IA clodronate. The secondary objectives of Phase III are: • to assess the effects of DTD on knee function by means of Lequesne Algofunctional Index and WOMAC index in patients with knee OA. • to measure the use of rescue drug consumption (paracetamol) in patients with knee OA treated with DTD.;Primary end point(s): A clodronate dose will be considered as effective when a = 10 mm reduction in the VAS of knee pain will be observed at Week 7 vs. Placebo;Timepoint(s) of evaluation of this end point: At week 7 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Mean changes in the VAS of knee pain observed 120 minutes after IA injection at Baseline, Weeks 1, 2 and 3 vs predose assessment; Mean changes in the VAS of knee pain observed at each other visit than Week 7 vs. Placebo and vs Baseline.; Mean changes in the Lequesne Algofunctional Index at each visit vs Placebo and vs Baseline.; Mean changes in the WOMAC Index at each visit vs Placebo and vs Baseline.; Mean changes in the Range of Motion at each visit vs Placebo and vs Base-line.; Use of rescue drug consumption (paracetamol) across the patients visits;Timepoint(s) of evaluation of this end point: At Baseline and at Weeks 1, 2 and 3; At each other visit than Week 7; At each visit; At each visit; At each visit; At each visit | — |
Countries
Italy
Contacts
Public ContactCRO
Pharmaceutical Development and Services srl
Outcome results
None listed