A Randomized, Double-Blind, Multi-Center, Placebo-Controlled, Trial to Evaluate the Efficacy and Safety of Once Daily Diclofenac Gel AMZ001 3.06% in the Treatment of Pain and Symptoms of Knee Osteoarthritis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Amzell B.V.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

30 Apr 2025 → 22 Dec 2025

Decision date (initial)

2025-04-30

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To compare the efficacy of diclofenac gel AMZ001 versus placebo for the treatment of pain, in terms of change in pain intensity evaluated by the WOMAC pain sub-score of the target knee, at week 2.

Secondary objectives 11

1. To evaluate changes in pain, in terms of the WOMAC pain sub-score of the target knee, at weeks 1, 3, 4, and 6
2. To evaluate changes in daily pain, in terms of the 11-point Pain Numeric Rating Scale (NRS) of the target knee until week 6.
3. To evaluate the onset of action of AMZ001, based on self-rated average pain scores in terms of the 11-point NRS 1 hour, 4 hours, 12 hours, 24 hours after the first drug application.
4. To evaluate changes as measured by Physician Global Assessment (PGA) at week 3 and 6
5. To evaluate changes in sleep, as measured by the Chronic Pain Sleep Inventory (CPSI), at weeks 3 and 6
6. To evaluate changes in physical functioning, in terms of the WOMAC function sub-score of the target knee, at weeks 1, 2, 3, 4 and 6
7. To evaluate the symptoms of osteoarthritis in terms of the WOMAC total score of the target knee, at weeks 3 and 6
8. To evaluate changes in quality of life, as measured by the EQ-5D-5L, at weeks 3 and 6
9. To evaluate changes as measured by the Osteoarthritis Research Society International Standing Committee for Clinical Trials Response Criteria Initiative and the Outcome Measures in Rheumatology Committee (OMERACT-OARSI) responder criteria, at weeks 3 and 6
10. To evaluate the use of rescue medication
11. To evaluate the safety and tolerability of AMZ001

Conditions and MedDRA coding

Knee Osteoarthritis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Participant is able to read and understand the language and content of the study material, understand the requirements for study visits, and is willing to provide information at the scheduled evaluations and appropriate written informed consent has been obtained.
2. Femorotibial OA of the knee, according to the American College of Rheumatology (ACR) clinical and radiographic criteria (Altman et al. 1986).
3. Radiological OA grade 2, or 3 of the target knee, using the Kellgren-Lawrence method (Kellgren and Lawrence 1957) as graded by central, independent reading of X-ray obtained during screening, or on a recent (within 6 months) X-ray image which fulfills the specifications for central reading.
4. Age between 40 years and 85 years at the time of screening, both included of either sex.
5. Pain score rated on an 11-point numerical rating scale of the target knee of ≥ 20 out of 50 in response to the WOMAC pain sub-score (5 questions), at the time of screening and baseline.
6. The WOMAC pain sub-score on the contralateral knee must not exceed the one on the target knee, regardless of the eligibility of the contralateral knee, at the time of screening and baseline.
7. At screening Visit 1a, participants report that their typical OA knee pain in one or both knees when not using medication is ≥ 4 out of 10.
8. Daily OA knee pain diary average numerical rating scale (NRS) score of ≥ 4 and ≤ 9 in the target knee, for the 7 days immediately preceding baseline (Day 1). The average calculation is based on the recorded scores during this entire period with a requirement of at least 4 days of data recorded.
9. Women of child-bearing potential must use a highly effective method of contraception (hormonal contraceptives, intrauterine device, vasectomy, bilateral tubal occlusion, sexual abstinence) from enrolment up to at least 3 months after the study end. Postmenopausal status is defined as being amenorrheic for at least 1 year prior to screening. Sexually active men with a female partner of childbearing potential must agree to use condom from enrolment up to at least 3 months after the study end.
10. Knee pain in the target knee for at least 14 days of the preceding month (periarticular knee pain due to OA and not due to non-OA conditions such as bursitis, tendonitis, etc.) based on participant report.
11. Except for OA, the participant is in reasonably good health as determined by the Investigator.

Exclusion criteria 22

1. Known or suspected hypersensitivity to or previous hypersensitivity reactions to diclofenac or of the excipients in either of the investigational products
2. Perioperative period in the setting of coronary artery bypass graft surgery.
3. Current malignancy or treatment for malignancy within the past five years, with the exception of non-melanoma skin cancer, unless affecting the target knee area, or carcinoma in situ events.
4. Any other abnormal laboratory results or significant medical conditions that the Investigator believes should preclude the participant’s participation in the trial.
5. Secondary OA of the target knee, previous procedures or trauma affecting joint homeostasis including total meniscectomy or septic arthritis, or any other serious condition leading to secondary OA of the target knee.
6. Reported incidence of any of the following diseases: known osteoarthritis of the hip(s) if pain in either or both hip(s) exceeds that of the target knee using the WOMAC hip pain sub-score, or presence of significant radicular back pain.
7. Presence of a defined cut-off of pain variability during the screening period of 1.5 out of 10: · Pain Numeric Rating Scale (NRS) scores must be recorded for the target knee on at least 4 out of the 7 days immediately preceding baseline (Day 1) · Observed standard deviation of the Daily osteoarthritis (OA) knee pain diary average NRS intensity score for 7 days immediately preceding baseline (Day 1) must not exceed 1.5
8. Estimated glomerular filtration rate (eGFR) < 30 mL/min using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI 2021) formula.
9. Generalized skin irritation, previous skin reactions upon use of topical NSAIDs, current skin irritation or redness at the planned site of gel application, or significant skin disease including psoriasis, as judged by the investigator.
10. Patients in whom asthma, angioedema, urticaria, or acute rhinitis are precipitated by acetylsalicylic acid or other non-steroidal anti-inflammatory drugs (NSAIDs).
11. Use of any topical medication on the planned application site within 15 days of the time of randomization.
12. Any use of opioid medication within 6 weeks before the screening visit.
13. Use of duloxetine, pregabalin, or gabapentin within 4 weeks before the screening visit.
14. History of alcohol or drug abuse within the past year prior to randomization.
15. Pregnant and breastfeeding women are excluded for participation.
16. Any physical impediment to gel application on the target knee.
17. Intra-articular delivery of corticosteroids or hyaluronic acid in the target knee within 6 months of screening or into any other joint within 30 days of screening.
18. High dose (equivalent to > 10 mg of prednisone/day) systemic corticosteroid treatment of more than 14 days during the past 6 months prior to screening.
19. Major surgery /arthroscopy of the target knee within the previous year prior to screening or aspiration of effusion of the target knee within 12 weeks prior to enrollment.
20. Planned surgery of the target knee within the next 12 months.
21. Use of a currently unapproved investigational drug, device or biologic within 3 months prior to screening.
22. Presence of concomitant non-osteoarthritic disease affecting either knee, such as rheumatoid arthritis, psoriasis, gout or clinically relevant pseudogout, if there is reason to believe that the disease(s) may significantly interfere with the interpretation of the clinical response to the study drug.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint of this trial is the change from baseline in WOMAC pain sub-score (questions 1 to 5) in the target knee as evaluated at week 2.

Secondary endpoints 16

1. Change from baseline in the WOMAC pain sub-score at week 1, in the target knee.
2. Change from baseline in pain at Day 8, Day 7, Day 6, Day 5, Day 4, Day 3, Day 2, and Day 1 using an 11-point Numeric Rating Scale (NRS).
3. Partial AUCs of the observed change from baseline based on pain recorded at 24 hours, 12 hours, 4 hours and 1 hour after the first drug application using an 11-point Numeric Rating Scale (NRS).
4. Change from baseline in PGA at weeks 3 and 6
5. Changes from baseline in the Chronic Pain Sleep Inventory at weeks 3 and 6
6. Change from baseline in the weekly average of daily pain recorded using an 11-point pain NRS until week 6 in the target knee
7. Change from baseline in the WOMAC pain sub-score during the trial in the target knee (week, 3, 4 and 6)
8. Change from baseline in the WOMAC function sub-score at during the trial (weeks 1,2, 3,4 and 6).
9. Change from baseline in the WOMAC total score during the trial (weeks 3 and 6).
10. Changes from baseline in quality of life as assessed using the EQ-5D-5L at weeks 3 and 6
11. Proportion of participants meeting the OMERACT-OARSI responder criteria at weeks 3 and 6
12. Proportion of participants meeting at least a 30 % reduction from baseline in WOMAC pain sub-score at Week 3 and 6.
13. Proportion of participants meeting at least a 50 % reduction from baseline in WOMAC pain sub-score at Week 3 and 6.
14. Time (days) to first use of rescue medication since baseline.
15. Average daily amount of rescue medication taken between visits.
16. Weekly proportion of days with rescue medication use at Weeks 1-6.

Investigational products

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

Test 1

Placebo 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Amzell B.V.

Sponsor organisation

Amzell B.V.

Address

Siriusdreef 31

City

Hoofddorp

Postcode

2132 WT

Country

Netherlands

Scientific contact point

Organisation

Amzell B.V.

Contact name

Head of R&D

Public contact point

Organisation

Amzell B.V.

Contact name

Amzell B.V.

Third parties 2

Locations

3 EU/EEA countries · 9 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 72 files

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

Application history

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