Clinical Trial to Assess Efficacy, Tolerability of Rising Doses of Clodronate in Painful Knee Osteoarthritis Patients

NCT06263517 | Unknown Phase 2

• 2 other identifiers: SPA-S-899-01-212021-003124-33
• Study Type: interventional
• Target: 296
• Locations: 1 country
• Sites: 11

Brief 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. 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

Conditions

Osteoarthritis of Knee

Keywords

Osteoarthritis; Osteoarthritis of Knee

Outcome Measures

Primary Outcomes (1)

• 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

  Week 7

Secondary Outcomes (6)

• VAS mean changes

  At Screening, at Baseline, at Weeks 1, 2, 3, 4, 5, 11, 15

• VAS mean changes observed 120 minutes after IA

  At Baseline and at Weeks 1, 2 and 3

• Lequesne Algofunctional Index mean changes

  At Screening, at Baseline, at Weeks 1, 2, 3, 4, 5, 7, 11, 15

• WOMAC mean changes

  At Screening, at Baseline, at Weeks 1, 2, 3, 4, 5, 7, 11, 15

• Range of motion mean changes

  At Screening, at Baseline, at Weeks 1, 2, 3, 4, 5, 7, 11, 15

Other Outcomes (3)

• SAE Reporting

  At Screening, at Baseline, at Weeks 1, 2, 3, 4, 5, 7, 11, 15

• AE Reporting

  At Screening, at Baseline, at Weeks 1, 2, 3, 4, 5, 7, 11, 15

• Clinical signs of intolerance Recording

  At Baseline, at Weeks 1, 2, 3, 4, 5, 7, 11, 15

Study Arms (4)

Arm 1

EXPERIMENTAL

Intra articular clodronate 2 mg/2 ml once a week for 4 weeks (total clodronate dose = 8 mg)

Drug: Clodronate

Arm 2

EXPERIMENTAL

Intra articular clodronate 5 mg/2 ml once a week for 4 weeks (total clodronate dose = 20 mg).

Drug: Clodronate

Arm 3

EXPERIMENTAL

Intra articular clodronate 10 mg/2 ml once a week for 4 weeks (total clodronate dose = 40 mg)

Drug: Clodronate

Arm 4

PLACEBO COMPARATOR

Placebo 2 ml once a week for 4 weeks (total clodronate dose = 0 mg).

Drug: Placebo

Interventions

Clodronate DRUG

For Arm 1, patients will be treated with intra articular clodronate 2 mg/2 ml from Baseline to Week 3

Arm 1

Placebo DRUG

For Arm 4, patients will be treated with Placebo 2 ml from Baseline to Week 3

Arm 4

Eligibility Criteria

• Age: 50 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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).

Sponsors & Collaborators

• SPA Società Prodotti Antibiotici S.p.A.: lead
• Pharmaceutical Development and Services: collaborator

Study Sites (11)

IRCCS Istituti Clinici Maugeri

Castel Goffredo, Mantova, 46042, Italy

RECRUITING

Ospedale San Pellegrino

Castiglione delle Stiviere, Mantova, 46043, Italy

RECRUITING

Ospedale Civile Servizio di Riabilitazione Funzionale

Volta Mantovana, Mantova, 46049, Italy

RECRUITING

Azienda Ospedaliera Universitaria San Luigi Gonzaga

Orbassano, Torino, 10043, Italy

NOT YET RECRUITING

Centro Riabilitativo Polifunzionale Teresio Borsalino

Alessandria, 15122, Italy

RECRUITING

IRCCS Ospedale Policlinico San Martino

Genova, 16132, Italy

RECRUITING

Ospedale Israelitico

Roma, 00148, Italy

RECRUITING

Ospedale San Pietro

Rome, 00189, Italy

RECRUITING

Ospedale San Paolo

Savona, 17100, Italy

NOT YET RECRUITING

Azienda Ospedaliero Universitaria Senese

Siena, 53100, Italy

RECRUITING

Ospedale Policlinico "G.B. Rossi" Borgo Roma

Verona, 37134, Italy

RECRUITING

MeSH Terms

Conditions

Osteoarthritis, Knee; Osteoarthritis

Interventions

Clodronic Acid

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Intervention Hierarchy (Ancestors)

Diphosphonates; Organophosphonates; Organophosphorus Compounds; Organic Chemicals

Central Study Contacts

Maria Rosa Galmozzi

CONTACT

0289139429; mariarosa.galmozzi@spafarma.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Randomization list will be performed with Proc Plan procedure by SAS ® Software (release 9.4 or later) software using the block randomization method with block size of 4. Subjects eligible at Baseline will be randomly allocated to receive 2, 5, 10 /2ml or placebo according to the balanced randomization list.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Adaptative, multicenter, randomized, double-blind, parallel-group, placebo controlled

Study Record Dates

• First Submitted: January 30, 2024
• First Posted: February 16, 2024
• Study Start: October 12, 2023
• Primary Completion: July 1, 2025
• Study Completion: October 1, 2025
• Last Updated: February 16, 2024

Record last verified: 2024-01

Locations

IT (11)