A study of the safety and efficacy of Diclofenac Gel AMZ001 3.06 % for the treatment of knee osteoarthritis symptoms.

Phase 1

Conditions: Knee Osteoarthritis
MedDRA version: 20.0 Level: LLT Classification code 10023476 Term: Knee osteoarthritis System Organ Class: 100000004859
Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Registration Number: EUCTR2018-001934-16-CZ

Lead Sponsor: Amzell BV

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Not specified

Target Recruitment: 440

Inclusion Criteria

1. Subject 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 osteoarthritis of the knee, according the American College of Rheumatology (ACR) clinical and radiographic criteria.
3. Radiological OA grade 1, 2, or 3 of the target knee, using the Kellgren-Lawrence method (KELLGREN & 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 and = 45 out of 50 in response to the WOMAC pain sub-score (5 questions), at the time of screening. The subject should have undergone a washout-period of at least 5 half-lives of any analgesic medication before completing the screening questionnaire.
6. Women of child-bearing potential must use at least an acceptably effective method of contraception (progestogen-only oral hormonal contraception, where inhibition of ovulation is not the primary mode of action, male or female condom with or without spermicide, cap, diaphragm or sponge with spermicide). 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.
7. Knee pain in the target knee for 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 subject report.
8. On stable pain therapy (i.e., at least 3 days per week for the previous
month) with an oral NSAID, or acetaminophen/paracetamol prior to the
Screening Visit.
9. Except for osteoarthritis, the subject is in reasonably good health as determined by the Investigator.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 290
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 150

Exclusion Criteria

1. Known or suspected hypersensitivity to or previous hypersensitivity reactions to diclofenac, other non-steroidal anti-inflammatory drugs or related substances including aspirin, any of the excipients in either of the investigational products, or any physical impediment to gel application on the target knee.
2. 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.
3. High dose (equivalent to > 5 mg of prednisone/day) systemic corticosteroid treatment of more than 14 days during the past 6 months prior to screening.
4. Major surgery or arthroscopy of the target knee within the previous year prior to screening.
5. Planned surgery of the target knee within the next 3 months.
6. Use of a currently unapproved investigational drug, device or biologic within 6 months prior to screening.
7. Presence of concomitant non-osteoarthritic disease affecting either knee, such as rheumatoid arthritis, psoriasis, gout or 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.
8. Medical history of coronary artery bypass graft surgery.
9. 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.
10. Any other abnormal laboratory results or significant medical conditions that the Investigator believes should preclude the subject's participation in the trial.
11. Secondary osteoarthritis 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.
12. 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 subscore, presence of
significant radicular back pain, or at least one migraine attack within the
past 12 months before screening, as reported by the subject
13. Presence of severe pain in either knee, defined as > 45 out of 50 in
response to the WOMAC pain sub-score (5 questions), at the time of
screening, regardless of the eligibility of the contralateral knee.
14. Body Mass Index > 45.0 kg/m2 .
15. Estimated glomerular filtration rate < 30 mL/min using the
Modification of Diet in Renal Disease (MDRD) method.
16. 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.
17. Known presence of gastroduodenal ulcer or any gastrointestinal bleeding (except hemorrhoidal) within 6 months prior to screening.
18. Use of any topical medication on the planned application site within
15 days of the time of randomization.
19. Use of moderate

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Timepoint(s) of evaluation of this end point: From baseline to week 4. Subjects will fill in the WOMAC questionnaire in all the visits (from the screening visit to visit 6).;<br> Main Objective: To evaluate the change in pain intensity, in terms of the WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) pain score of the target knee<br> ;Primary end point(s): 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 4.;<br> Secondary Objective: - To evaluate changes in symptoms of OA<br> - To evaluate the changes in physical functioning<br> - To evaluate administration regimens of AMZ001<br> - To evaluate the safety and tolerability of AMZ001<br> - To evaluate changes in quality of life<br> <br>

Secondary Outcome Measures

Name	Time	Method

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