Osteoarthritis of KneePhase 2/3NCT06263517
Clinical Trial to Assess Efficacy, Tolerability of Rising Doses of Clodronate in Painful Knee Osteoarthritis Patients
A Phase 2/3 study testing Clodronate in people with Osteoarthritis of Knee, run by SPA Società Prodotti Antibiotici S.p.A. at 11 sites in Italy.
Trial summary
The goal of this clinical trial is to to clarify which is the best dose of administration, to select a dose and to confirm the therapeutic efficacy of clodronate in patients with painful knee osteoarthritis (OA). The clinical trial will be divided in two parts. Read more about this study
- Who is it for?
- Ages 50 to 75 years
- Conditions the study is for
- Osteoarthritis of Knee
- What is being tested?
- Clodronate
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 296 participants
- Where
- 11 sitesItaly
- Study dates
- 12 Oct 2023to Oct 2025
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Female and male patients aged 50 up to 75 years at ICF signature.
- Diagnosis of knee OA according to the American College of Rheumatology, confirmed by Rx during the screening (a Rx performed in the last 3 months before Baseline is accepted).
- Kellgren-Lawrence radiographic score between 2 and 3 degrees in the tibiofemoral joint.
- Symptomatic knee OA (pain) since at least 6 months with a knee pain (VAS) ranging between 40 and 80 mm at Screening visit (the figure should be confirmed at Baseline).
- Female patients of childbearing potential must have a negative pregnancy test before each treat-ment and during the Visit 5 - Week 4 and they must use adequate methods of contraception throughout the course of the study.
- A signed ICF by the patient after exhaustive study discussion with the investigators.
Who cannot join
- 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 3 months before Day 0 - Baseline (including any formulation of corticosteroids or hyaluronic acid injections).
- Corticosteroid use by any systemic route, and hyaluronic acid injection or intraarticular corticosteroids for any other joint in the previous month will not be permitted.
Show all 27Show fewer
- Any treatment with systemic non-steroidal anti-inflammatory drugs (NSAIDs) in the week before enrolment, or any steroid anti-inflammatory drugs and chondroprotective drugs in the thirty (30) days before month before Baseline.
- 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 Baseline.
- Any treatment with Denosumab in the twelve (12) months before Baseline.
- Any treatment with Paracetamol in the twelve (12) hours before Baseline.
- 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 Baseline or at a risk of jaw osteonecrosis.
- Any known hypersensitivity to the drug in the study 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:
- Absolute Neutrophil Count (ANC) < 1500/μl.
- Hemoglobin (Hb) < 9 g/dl (< Hb 5.6 mmol/L)
- Platelet Count < 100.000/μl
- Serum Creatinine > 1.5 x Upper limit normal (ULN) or estimated Glomerular Filtration Rate (eGFR) < 60 mL/min (as per Cockroft-Gault formula).
- Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST)> 1.5 x Upper limit normal(ULN).
- Serum Total Bilirubin > 1.5 x Upper limit normal (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.
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
Italy11 sites, 11 recruiting
- Recruiting
Centro Riabilitativo Polifunzionale Teresio Borsalino
Alessandria, 15122
Marco Invernizzi
- Recruiting
IRCCS Istituti Clinici Maugeri
Castel Goffredo, Mantova, 46042
Lul Abdi-Ali
- Recruiting
Ospedale San Pellegrino
Castiglione delle Stiviere, Mantova, 46043
Paolo Roberto Ferrari
- Recruiting
IRCCS Ospedale Policlinico San Martino
Genova, 16132
Matteo Formica
- Not yet recruiting
Azienda Ospedaliera Universitaria San Luigi Gonzaga
Orbassano, Torino, 10043
Filippo Castoldi
- Recruiting
Ospedale Israelitico
Roma, 00148
Maria Chiara Meloni
- Recruiting
Ospedale San Pietro
Rome, 00189
Alberto Migliore
- Not yet recruiting
Ospedale San Paolo
Savona, 17100
Danilo Chiapale
- Recruiting
Azienda Ospedaliero Universitaria Senese
Siena, 53100
Bruno Frediani
- Recruiting
Ospedale Policlinico "G.B. Rossi" Borgo Roma
Verona, 37134
Luca Dalle Carbonare
- Recruiting
Ospedale Civile Servizio di Riabilitazione Funzionale
Volta Mantovana, Mantova, 46049
Luisa Selletti
About this study
Official title: Adaptative, Multicenter, Randomized, Double-blind, Parallel-group, Placebo Controlled, Clinical Trial, on the Efficacy and Tolerability of Different Escalating Doses of Intra-articular Clodronate in Patients With Painful Knee Osteoarthritis
The goal of this clinical trial is to to clarify which is the best dose of administration, to select a dose and to confirm the therapeutic efficacy of clodronate in patients with painful knee osteoarthritis (OA). The clinical trial will be divided in two parts.
The main questions it aims to answer are:
- in Phase II, to assess the safety and tolerability of different escalating doses of intra articular (IA) clodronate
- in Phase II, to set a defined therapeutic dose (DTD) to be used in Phase III
- in Phase III, to assess the safety and tolerability of different escalating doses of IA clodronate to confirm and extensively evaluate the therapeutic efficacy and safety of the clodronate DTD in patients with knee OA
Read the detailed description
The phase II will be a multicenter, double-blind, randomized, placebo-controlled, parallel group four-arm study, according to the treatment dose (dose finding).
Briefly, 4 groups of 74 patients (in order to have 64 fully evaluated patients taking into consideration 10 patients dropped out), i.e. a total of 296 patients, with knee OA each will be randomly allocated to the following treatments:
- IA clodronate 2 mg/2 ml once a week for 4 weeks (total clodronate dose = 8 mg).
- IA clodronate 5 mg/2 ml once a week for 4 weeks (total clodronate dose = 20 mg).
- IA clodronate 10 mg/2 ml once a week for 4 weeks (total clodronate dose = 40 mg).
- Placebo 2 ml once a week for 4 weeks (total clodronate dose = 0 mg).
At the end of phase II, the minimum effective clodronate dose will be selected as DTD for the Phase III.
The phase III will be a multicenter, double-blind, randomized, placebo-controlled, two parallel groups (DTD vs. placebo) study.
Briefly, patients with knee OA will be randomly assigned to two experimental groups:
- the DTD defined during the Phase II.
- Matching placebo. The sample size of Phase III will be definitively calculated according to the extent of pain Visual Analogue Scale (VAS) reduction observed in the Phase II.
- Conditions
- Osteoarthritis of Knee
- Being tested
- Clodronate, Placebo
- Keywords
- Osteoarthritis, Osteoarthritis of Knee
- Medical subject headings
- Osteoarthritis, Knee, Osteoarthritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ClodronateDrug
For Arm 1, patients will be treated with intra articular clodronate 2 mg/2 ml from Baseline to Week 3
ClodronateDrug
For Arm 2, patients will be treated with intra articular clodronate 5 mg/2 ml from Baseline to Week 3
ClodronateDrug
For Arm 3, patients will be treated with intra articular clodronate 10 mg/2 ml from Baseline to Week 3
PlaceboDrug
For Arm 4, patients will be treated with Placebo 2 ml from Baseline to Week 3
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | Intra articular clodronate 2 mg/2 ml once a week for 4 weeks (total clodronate dose = 8 mg) Receives: Drug: Clodronate |
| Arm 2 | Experimental | Intra articular clodronate 5 mg/2 ml once a week for 4 weeks (total clodronate dose = 20 mg). Receives: Drug: Clodronate |
| Arm 3 | Experimental | Intra articular clodronate 10 mg/2 ml once a week for 4 weeks (total clodronate dose = 40 mg) Receives: Drug: Clodronate |
| Arm 4 | Placebo comparator | Placebo 2 ml once a week for 4 weeks (total clodronate dose = 0 mg). Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy: VAS Reduction
A clodronate dose will be considered as effective when a ≥ 10 mm reduction in the Visual Analogue Scale (VAS) of knee pain will be observed at Week 7 vs. Placebo
Measured: Week 7
Secondary outcomes (6)
VAS mean changes
Mean changes in the Visual Analogue Scale (VAS) of knee pain observed at each other visit than Week 7 vs. Placebo and vs Baseline.
Measured: At Screening, at Baseline, at Weeks 1, 2, 3, 4, 5, 11, 15
VAS mean changes observed 120 minutes after IA
Mean changes in the Visual Analogue Scale (VAS) of knee pain observed 120 minutes after IA injection at Baseline, Weeks 1, 2 and 3 vs predose assessment
Measured: At Baseline and at Weeks 1, 2 and 3
Lequesne Algofunctional Index mean changes
Mean changes in the Lequesne Algofunctional Index at each visit vs Placebo and vs Baseline.
Measured: At Screening, at Baseline, at Weeks 1, 2, 3, 4, 5, 7, 11, 15
WOMAC mean changes
Mean changes in the (WOMAC) Western Scale Ontario MacMaster Index at each visit vs Placebo and vs Baseline.
Measured: At Screening, at Baseline, at Weeks 1, 2, 3, 4, 5, 7, 11, 15
Range of motion mean changes
Mean changes in the Range of Motion at each visit vs Placebo and vs Baseline.
Measured: At Screening, at Baseline, at Weeks 1, 2, 3, 4, 5, 7, 11, 15
Paracetamol consumption
Use of rescue drug consumption (paracetamol) across the patients visits
Measured: At Baseline, at Weeks 1, 2, 3, 4, 5, 7, 11, 15
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Feb 2024
- Study start12 Oct 2023
- Primary completionJul 2025 (estimated)
- Study completionOct 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Osteoarthritis of KneeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Adaptative, multicenter, randomized, double-blind, parallel-group, placebo controlled
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 296 participants (estimated)
Sponsor and investigators
- Lead sponsor
- SPA Società Prodotti Antibiotici S.p.A.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Pharmaceutical Development and Services
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06263517
- Sponsor's protocol ID
- SPA-S-899-01-21
- Other IDs
- 2021-003124-33
- Status last verified
- Jan 2024
- First submitted
- 30 Jan 2024
- Last updated
- 16 Feb 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Adaptative, Multicenter, Randomized, Double-blind, Parallel-group, Placebo Controlled, Clinical Trial, on the Efficacy and Tolerability of Different Escalating Doses of Intra-articular Clodronate in Patients With Painful Knee Osteoarthritis
- ClinicalTrials.gov ID
- NCT06263517
- Acronym / sponsor ID
- SPA-S-899-01-21
- Conditions
- Osteoarthritis of Knee
- Keywords
- Osteoarthritis, Osteoarthritis of Knee
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 296 participants (estimated)
- Lead sponsor
- SPA Società Prodotti Antibiotici S.p.A.Industry (pharma, biotech, devices)
- Collaborators
- Pharmaceutical Development and Services
- Study start
- 12 Oct 2023 (actual)
- Primary completion
- Jul 2025 (estimated)
- Study completion
- Oct 2025 (estimated)
- First posted
- 16 Feb 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical trial is to to clarify which is the best dose of administration, to select a dose and to confirm the therapeutic efficacy of clodronate in patients with painful knee osteoarthritis (OA). The clinical trial will be divided in two parts.
The main questions it aims to answer are:
- in Phase II, to assess the safety and tolerability of different escalating doses of intra articular (IA) clodronate
- in Phase II, to set a defined therapeutic dose (DTD) to be used in Phase III
- in Phase III, to assess the safety and tolerability of different escalating doses of IA clodronate to confirm and extensively evaluate the therapeutic efficacy and safety of the clodronate DTD in patients with knee OA
Detailed description
The phase II will be a multicenter, double-blind, randomized, placebo-controlled, parallel group four-arm study, according to the treatment dose (dose finding).
Briefly, 4 groups of 74 patients (in order to have 64 fully evaluated patients taking into consideration 10 patients dropped out), i.e. a total of 296 patients, with knee OA each will be randomly allocated to the following treatments:
- IA clodronate 2 mg/2 ml once a week for 4 weeks (total clodronate dose = 8 mg).
- IA clodronate 5 mg/2 ml once a week for 4 weeks (total clodronate dose = 20 mg).
- IA clodronate 10 mg/2 ml once a week for 4 weeks (total clodronate dose = 40 mg).
- Placebo 2 ml once a week for 4 weeks (total clodronate dose = 0 mg).
At the end of phase II, the minimum effective clodronate dose will be selected as DTD for the Phase III.
The phase III will be a multicenter, double-blind, randomized, placebo-controlled, two parallel groups (DTD vs. placebo) study.
Briefly, patients with knee OA will be randomly assigned to two experimental groups:
- the DTD defined during the Phase II.
- Matching placebo. The sample size of Phase III will be definitively calculated according to the extent of pain Visual Analogue Scale (VAS) reduction observed in the Phase II.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
- Model description
- Adaptative, multicenter, randomized, double-blind, parallel-group, placebo controlled
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Experimental | Drug: ClodronateIntra articular clodronate 2 mg/2 ml once a week for 4 weeks (total clodronate dose = 8 mg) |
| Arm 2 | Experimental | Drug: ClodronateIntra articular clodronate 5 mg/2 ml once a week for 4 weeks (total clodronate dose = 20 mg). |
| Arm 3 | Experimental | Drug: ClodronateIntra articular clodronate 10 mg/2 ml once a week for 4 weeks (total clodronate dose = 40 mg) |
| Arm 4 | Placebo comparator | Drug: PlaceboPlacebo 2 ml once a week for 4 weeks (total clodronate dose = 0 mg). |
Who may qualify
- Ages
- 50 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Female and male patients aged 50 up to 75 years at ICF signature.
- Diagnosis of knee OA according to the American College of Rheumatology, confirmed by Rx during the screening (a Rx performed in the last 3 months before Baseline is accepted).
- Kellgren-Lawrence radiographic score between 2 and 3 degrees in the tibiofemoral joint.
- Symptomatic knee OA (pain) since at least 6 months with a knee pain (VAS) ranging between 40 and 80 mm at Screening visit (the figure should be confirmed at Baseline).
- Female patients of childbearing potential must have a negative pregnancy test before each treat-ment and during the Visit 5 - Week 4 and they must use adequate methods of contraception throughout the course of the study.
Key exclusion criteria (27 listed)
- 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 3 months before Day 0 - Baseline (including any formulation of corticosteroids or hyaluronic acid injections).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ClodronateFor Arm 1, patients will be treated with intra articular clodronate 2 mg/2 ml from Baseline to Week 3 | Drug | Arm 1 |
| ClodronateFor Arm 2, patients will be treated with intra articular clodronate 5 mg/2 ml from Baseline to Week 3 | Drug | Arm 2 |
| ClodronateFor Arm 3, patients will be treated with intra articular clodronate 10 mg/2 ml from Baseline to Week 3 | Drug | Arm 3 |
| PlaceboFor Arm 4, patients will be treated with Placebo 2 ml from Baseline to Week 3 | Drug | Arm 4 |
Primary outcome
Efficacy: VAS Reduction
Time frame: Week 7
A clodronate dose will be considered as effective when a ≥ 10 mm reduction in the Visual Analogue Scale (VAS) of knee pain will be observed at Week 7 vs. Placebo
6 secondary outcomes
VAS mean changes
Time frame: At Screening, at Baseline, at Weeks 1, 2, 3, 4, 5, 11, 15
VAS mean changes observed 120 minutes after IA
Time frame: At Baseline and at Weeks 1, 2 and 3
Lequesne Algofunctional Index mean changes
Time frame: At Screening, at Baseline, at Weeks 1, 2, 3, 4, 5, 7, 11, 15
WOMAC mean changes
Time frame: At Screening, at Baseline, at Weeks 1, 2, 3, 4, 5, 7, 11, 15
Range of motion mean changes
Time frame: At Screening, at Baseline, at Weeks 1, 2, 3, 4, 5, 7, 11, 15
Paracetamol consumption
Time frame: At Baseline, at Weeks 1, 2, 3, 4, 5, 7, 11, 15
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Feb 2024.
Related trials for Osteoarthritis of Knee
Not yet recruiting
Holistic Healing for Knee Osteoarthritis
Knee Osteoarthritis (Knee OA)
Recruiting
Effect of Anti-inflammatory Diet in Osteoarthritis
Osteoarthritis, Knee
Active, not recruitingPhase 2/3
Single vs Triple Hyaluronic Acid in Knee Osteoarthritis
Osteoarthritis, Knee
Not yet recruiting
The Feasibility of a Virtual/Home-based OA Treatment Program in Older Adults With OA and Multimorbidity
Osteoarthritis of the Knee
RecruitingObservational study
Exploring Factors Linked to Worsening Over Time in People With Early-stage Knee Osteoarthritis and Those With Prior Proven Acute Knee Injury.
Knee Osteoarthritis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Clodronate in people with Osteoarthritis of Knee, run by SPA Società Prodotti Antibiotici S.p.A. at 11 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 16 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Maria Rosa Galmozzi (0289139429 ext. +39, mariarosa.galmozzi@spafarma.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Efficacy: VAS Reduction (time frame: Week 7). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Feb 2024.