A randomized, multi-centre, double-blind, phase II clinical trial of dose finding of Montelukast in patients with erosive osteoarthritis of the hands. HOME study.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Farmalider S.A.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

11 Jan 2024 → 17 Sep 2024

Decision date (initial)

2023-11-06

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Laboratorios Farmalíder, S.A.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

The primary objective of the study is to evaluate the difference in pain intensity of the most affected hand at 8 weeks of treatment with different doses of Montelukast, compared to placebo, in patients with erosive hand osteoarthritis (EHOA), using the Visual Analogue Scale (VAS).

Secondary objectives 8

1. To evaluate the difference in pain intensity of the most affected hand at 4 weeks of treatment with different doses of Montelukast, compared to placebo, in patients with EHOA, using the VAS
2. To evaluate the difference in pain, stiffness, and physical function of the most affected hand at 4 and 8 weeks of treatment with the different doses of Montelukast, compared to placebo, using the AUSCAN questionnaire
3. Evaluate the difference in the hand grip strength of the most affected hand at 4 and 8 weeks of treatment with different doses of Montelukast, compared to placebo, using a dynamometer.
4. Evaluate the proportion of patients using rescue medication at 4 and 8 weeks of treatment with different doses of Montelukast, compared to placebo.
5. Evaluate the amount of rescue medication used at 4 and 8 weeks of treatment with different doses of Montelukast, compared to placebo.
6. Evaluate the difference in the quality of life of the different treatment groups, compared to placebo, at 4 and 8 weeks, using the EuroQol-5D-5L Questionnaire.
7. Evaluate the differences in difficulty sleeping due to pain of the most affected hand of the different treatment groups, compared to placebo, at 4 and 8 weeks, using a generic question
8. Evaluate the safety and tolerability of the different doses of Montelukast used in the study, compared with placebo.

Conditions and MedDRA coding

Erosive osteoarthritis of the hands

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Patients who provide written informed consent and are willing to comply with all scheduled visits and procedures required by the study.
2. Patients ≥ 18 years at the time of the baseline visit.
3. Patients with erosive osteoarthritis of the interphalangeal joints of the hand with significant clinical activity according to Anandarajah criteria.
4. Patients with VAS pain of the most affected hand ≥ 50 mm at the baseline visit.
5. Patients with repercussion in functionality of the most affected hand evaluated with a score ≥2 in the question number 12 (carrying a full pot with one hand) of the function subscale of the AUSCAN Questionnaire.

Exclusion criteria 17

1. History of fibromyalgia and/or chronic fatigue syndrome.
2. Patient with pathologies that according to medical criteria discourage their participation in the study, such as poorly controlled neuropsychiatrics diseases, severe heart disease, liver failure, kidney failure, active malignancies, poorly controlled endocrine-metabolic diseases, coagulopathies, active gastrointestinal ulceration, active infection, epilepsy, and immunocompromised patients.
3. Patient with a history of concurrent rheumatic articular diseases (history and/or current presence of signs) that could lead to a misinterpretation or interfere in the evaluation of efficacy in pain, such as chondrocalcinosis, Paget's disease of the ipsilateral extremity in relation to the affected hand, rheumatoid arthritis, aseptic osteonecrosis, gout, septic arthritis, ochronosis, acromegaly, hemochromatosis, Wilson's disease, osteochondromatosis, seronegative spondyloarthropathy, mixed connective tissue disease, collagen vascular disease, psoriasis and disease Inflammatory bowel (Crohn's disease or Ulcerative Colitis).
4. Pain in another part of the body that could interfere with the evaluation and results of the study according investigator criteria.
5. Patient taking corticosteroids (oral or injectable) within 4 weeks prior to the baseline visit, or methotrexate, hydroxychloroquine or SYSADOAs (Slow-Acting Drugs for the Symptomatic Treatment of Osteoarthritis) within 12 weeks prior to the baseline visit.
6. Patients who have used intra-articular hyaluronic acid (in the study hand) during the 24 weeks prior to the baseline visit.
7. Patient undergoing radioactive synoviorthesis (in the study hand).
8. Patient being treated with other disease-modifying anti-rheumatic biological drugs.
9. Patient being treated with any other medication contraindicated due to risk of interactions with study medication.
10. Patient being treated with NSAIDs* and/or analgesics (except paracetamol) or colchicine within 7 days prior to the baseline visit. The use of paracetamol will be allowed up to 24 hours prior to the start of study treatment. *The sporadic use of Ibuprofen in case of an intercurrent disease other than EHOA will be allowed up to 96 hours prior to the screening visit (visit 0), or, to the visit 1. Maximum daily dose of ibuprofen allowed will be 1200mg.
11. Patient with a history of allergy or hypersensitivity to the study medication, rescue medication or any of its excipients.
12. Patient intolerant to study medication due to galactose intolerance, lactase insufficiency, or glucose-galactose malabsorption.
13. Pregnant or lactating women.
14. Women of childbearing age and sexually active (excluded from this definition are women whose date of last menstruation is greater than one year from inclusion in this study and those who have undergone a tubal ligation or hysterectomy), who do not agree to take contraceptive measures during the clinical trial. Contraceptive measures include barrier methods, hormonal contraception, intrauterine device (IUD), or sexual abstinence. The investigator is responsible for determining whether the subject has adequate birth control for study participation.
15. Patient currently included in or who have participated in a clinical trial with medicines or health products in the 3 months prior to the baseline visit.
16. Patients with scheduled surgery during the clinical trial
17. History of drug or alcohol abuse during the 12 months prior to the baseline visit.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Difference in pain intensity (PID) of the most affected hand with respect to baseline pain at 8 weeks of treatment with different doses of Montelukast of 5, 10, 15 and 30 mg, compared to placebo, measured through the Visual Analogue Scale (VAS).

Secondary endpoints 11

1. EFFICACY ENDPOINTS:The PID with respect to baseline pain of the most affected hand at 4 weeks of treatment with different doses of Montelukast of 5, 10, 15 and 30 mg, compared to placebo, measured through the VAS
2. Difference in the score of AUSCAN subscales (pain, stiffness and physical function) of the most affected hand with respect to baseline at 4 and 8 weeks of treatment with different doses of Montelukast of 5, 10, 15 and 30 mg, compared to placebo.
3. Difference in the hand grip strength of the most affected hand with respect to baseline at 4 and 8 weeks of treatment with different doses of Montelukast 5, 10, 15 and 30 mg, compared to placebo, measured using a dynamometer (previously inflated to 60 mmHg).
4. Proportion of patients using rescue medication at 4 and 8 weeks of treatment with different doses of Montelukast 5, 10, 15 and 30 mg, compared to placebo.
5. Amount of rescue medication used in each treatment group, compared to placebo at 4 and 8 weeks of treatment with different doses of Montelukast 5, 10, 15 and 30 mg.
6. Difference in the quality of life with respect to baseline at 4 and 8 weeks of treatment with different doses of Montelukast 5, 10, 15 and 30 mg, compared to placebo, using the EuroQol-5D-5L quality of life questionnaire.
7. Difference in the sleeping difficulty due to pain of the most affected hand with respect to baseline at 4 and 8 weeks of treatment, using a generic question: “During the last week, how many times have you had trouble sleeping because of pain in your hand?”.
8. SAFETY ENDPOINTS: Vital signs (body temperature, heart rate, blood pressure) and physical examination at baseline, 4 and 8 weeks.
9. Analytical parameters at baseline and 8 weeks of treatment.
10. Adverse events throughout the study.
11. EFFICACY ENDPOINT: Difference in the AUSCAN total score of the most affected hand with respect to baseline at 4 and 8 weeks of treatment with different doses of Montelukast of 5, 10, 15 and 30 mg, compared to placebo.

Investigational products

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

Test 4

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Farmalider S.A.

Sponsor organisation

Farmalider S.A.

Address

Calle De La Granja 1 Planta 3

City

Alcobendas

Postcode

28108

Country

Spain

Scientific contact point

Organisation

Farmalider S.A.

Contact name

María Angeles Rodríguez

Public contact point

Organisation

Farmalider S.A.

Contact name

María Angeles Rodríguez

Third parties 1

Locations

1 EU/EEA country · 5 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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 3 files

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

Application history

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