International study to compare the efficacy and safety of chondroitin sulfate 800 mg tablets of two different origins (bovine versus marine) in the treatment of knee osteoarthritis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

IBSA Institut Biochimique SA

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

7 Aug 2025 → ongoing

Decision date (initial)

2025-04-09

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To demonstrate the non-inferiority of efficacy of bovine chondroitin sulfate (CS) 800 mg tablets versus marine chondroitin sulfate (CS) 800 mg tablets taken for 24 weeks (6 months), in the treatment of pain and functional impairment due to knee osteoarthritis (OA).

Secondary objectives 5

1. To assess the efficacy of the two investigational medicinal products (IMPs) on quality of life in patients with knee OA;
2. To assess the patient’s and Investigator’s evaluation of the efficacy of the two IMPs;
3. To assess the consumption of rescue medication for the treatment of pain due to knee OA;
4. To assess the compliance to treatment with the two IMPs;
5. To assess the safety of the two IMPs.

Conditions and MedDRA coding

Knee osteoarthritis with moderate to severe pain

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Voluntarily given informed consent to study participation in writing encompassing consent to personal data processing;
2. Outpatient of either sex, aged ≥ 50 years;
3. Patients affected by knee OA, as defined by American College of Rheumatology (ACR) clinical and radiographic criteria;
4. History of knee OA in one or both knees for > 6 months (including regular pain and functional impairment) as confirmed by the Investigator, based on available written documentation and/or patient reporting;
5. Radiographic findings of knee OA classified by Kellgren-Lawrence (K-L) grade of 2 or 3 based on an antero-posterior weight-bearing X-ray view of the target knee taken within 6 months prior to inclusion in the study. In the case that a patient has not a valid X-ray within 6 months prior to screening, the exam has to be performed during the screening period (in case that both knees have an equal intensity of pain, the target knee will be selected subjectively by the Investigator on the basis of the X-ray that will be requested for both knees);
6. Pain in the target knee verifying the following conditions: A mean score of ≥ 5 to ≤ 9 on the 24-hour average daily pain score in the target knee (on a 0-10 numeric rating scale [NRS]), where the mean is calculated over all values that are available in the 7 days prior to randomization (Day 1), and it is required that at least 5 pain score values will be available during that period; - An individual 24-hour average daily pain score in the target knee ≥ 1and ≤ 9 for all values that are available in the 7 days prior to randomization (Day 1);
7. Functional impairment in the target knee, with a mean score ≥ 3 to ≤ 9 (on a 0-10 NRS) in the Western Ontario andMcMaster Universities Arthritis Index (WOMAC®) function subscale at the baseline visit. To be eligible for the study, it is also required that patients will be able to respond at least 14 items of the WOMAC® physical function subscale, with a maximum of 3 unanswered items
8. Patient is able to understand and follow the study requirements and is familiar with the use of electronic devices;
9. If female of child-bearing potential, patient is non-lactating and non- pregnant, and must have a negative urine pregnancy test at the screening visit and use a reliable form of contraception throughout the study. Note: to be considered females of non-child-bearing potential, females must be postmenopausal for at least 1 year or surgically sterile [bilateral tubal ligation, bilateral oophorectomy or hysterectomy]) or practicing one of the following medically acceptable methods of birth control: - Hormonal methods such as oral, implantable, injectable or transdermal contraceptives before IMP administration. - Agrees to abstain from heterosexual intercourse during study participation and to use a highly effective contraceptive (as described above) if they become sexually active during the study. Abstinence is only acceptable if this is the patient’s usual lifestyle. Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhea method are not acceptable methods of contraception. - Intrauterine device. - Double-barrier method (condoms, sponge, diaphragm, with spermicidal jellies, or cream).

Exclusion criteria 20

1. Patients with predominantly patella-femoral OA defined as moderate to severe femoro-patellar OA with only no or mild femoro-tibial OA;
2. Patients with severe ipsilateral hip OA that could possibly confound the patient’s assessment of target knee pain in the judgement of the Investigator;
3. Patients having had surgery of the target knee in the past 6 months (for arthroscopic surgery) or 12 months (for osteotomy or other surgery) prior to screening, had knee lavage in the target knee in the 6 months prior to screening, and/or significant injuries to the target knee in the 6 months prior to screening, or had knee replacement surgery on the target knee ever or has planned knee surgery on the target knee during the study;
4. Patients with body mass index (BMI) ≥ 34 kg/m2;
5. Patients with large intra-articular effusion of the target knee requiring arthrocentesis or active infection of the target knee;
6. Patients with significant pain outside the target knee, including significant back pain;
7. Patients with excessive malalignment (i.e. genu varum or valgum) that would justify an osteotomy;
8. Patients with clinically significant ligamentous laxity, or meniscal instability as assessed by the Investigator;
9. Patients with any musculoskeletal condition affecting the target knee that would impair assessment of the effectiveness in the knee;
10. Patients with systemic inflammatory arthropathies (rheumatic disease, inflammatory or infective joint diseases or systemic lupus; recurrent clinical chondrocalcinosis; crystal arthropathies), metabolic joint diseases, osteo-articular pathologies differing from arthrosis, ochronosis, acromegaly, collagen gene mutations, or metabolic arthropathies or Paget’s illness;
11. Patients with widespread chronic musculoskeletal pain syndrome (e.g., fibromyalgia);
12. Patients with an allergy or hypersensitivity to the active substance or to any other ingredient of the IMP (i.e., CS tablets) or has a strict vegan (i.e., does not consume fish-based or meat-based products) lifestyle;
13. Patients with any clinically severe or significant uncontrolled concurrent disease that could interfere with the outcome of the study or the patient’s ability to comply with study requirements;
14. Patients with any other concurrent diseases requiring chronic use of analgesics/non-steroidal anti-inflammatory drugs (NSAIDs);
15. Patients having received: - Corticosteroids by systemic administration (oral or parenteral) in the past 30 days prior to the inclusion or corticosteroid by intra- articular administration in the past 3 months prior to the inclusion. Patients on treatment with inhaled corticosteroids can be included in the study; - Systemic short-acting (with a half-life ≤ 6 hours) (e.g., ibuprofen, ketoprofen) or long-acting NSAIDs (e.g., piroxicam, naproxen). The wash-out period begins ≥ 5 half-lives of the drug prior to Day -7 and needs to be completed prior to Day -7. For patients taking these drugs at the screening visit, patients may continue taking these drugs, provided that the indicated wash-out period is respected from 7 days prior to randomization (Day 1); - Hypnotics, muscle relaxants and anxiolytics: if intake has started < 8 days before screening and wash-out not completed prior to Day - 7; - Paracetamol or other analgesics (washout period begins ≥ 5 half- lives of the drug prior to Day -7 and needs to be completed prior to Day -7). Note: patients will be informed that, if strictly necessary, they can take rescue medication (paracetamol) in the period before Day 1 (Visit 2, baseline visit) with the exception of the 24 hr before Day 1 (Visit 2, baseline visit); - Basic treatment of arthritis with food supplements for joint care (CS, glucosamine sulphate, diacereine, hyaluronic acid, etc.) within 6 months prior to the inclusion; - Viscosupplementation, tidal lavage, platelet-rich plasma, or stem cell injection within 6 months prior to the inclusion; - Planned treatments with physical or other alternative therapies (i.e. laser therapy, ultrasound therapy, antalgic electrotherapy, tecar therapy, physiotherapy, mesotherapy, acupuncture) for the duration of the study period;
16. Patients with presence of clinically relevant psychiatric illness hindering the protocol compliance;
17. Patients with known and documented renal and/or hepatic and/or heart failure;
18. Concomitant participation in other clinical trials or participation in the evaluation of any investigational product during 3 months before this study or previous participation in the same study; months before this study or previous participation in the same study;
19. Participation in the study is also not permitted to employees of the Investigator or study site with direct involvement in the trial or in other trials under the direction of that Investigator, as well as family members of the employees or of the Investigator;
20. At the Baseline visit, patients not compliant with e-Diary use (i.e., has < 5 entries in the e-Diary during the last 7 days before the Day 1/Baseline).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Change from Baseline to Week 24 in the weekly mean (7-day average) of the average daily pain in the target knee as measured by the NRS (0-10 points);
2. Change from Baseline to Week 24 in mean score of WOMAC® function subscale, as measured by the NRS (0-10 points).

Secondary endpoints 8

1. Change from Baseline to each week until Week 24 in the weekly mean of the average daily pain in the target knee as measured with the NRS;
2. Change from Baseline to end of follow-up period (i.e. 12 weeks after the end of treatment) of the daily (24-hour) pain in the target knee as measured with the NRS;
3. Responder rates at each visit using 2 different response definitions (≥ 30% or ≥ 50% decrease versus Baseline in weekly mean of the average daily (24-hour) NRS pain intensity score);
4. Change from Baseline to Weeks 4, 12 and 24 in mean WOMAC® total score and all mean WOMAC® subscores (except for the primary endpoint change from Baseline to Week 24 in mean score of WOMAC® function subscale);
5. Change from Baseline to Weeks 4, 12 and 24 in patient’s quality of life (EQ-5D-5L);
6. Patient’s global evaluation at Weeks 4, 12, and 24 as measured by PGIC using a 5-point rating scale;
7. Investigator’s global evaluation at Weeks 4, 12 and 24 as measured by CGIC using a 5-point rating scale;
8. Consumption of rescue medication (paracetamol), including the number and proportion of users, the number of daily intakes and total dose per day.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

IBSA Institut Biochimique SA

Sponsor organisation

IBSA Institut Biochimique SA

Address

Via Pian Scairolo 49

City

Pazzallo

Postcode

6912

Country

Switzerland

Scientific contact point

Organisation

IBSA Institut Biochimique SA

Contact name

R&D Scientific Affairs Manager

Public contact point

Organisation

IBSA Institut Biochimique SA

Contact name

R&D Scientific Affairs Manager

Locations

3 EU/EEA countries · 30 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 35 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications