A Trial of APPA in the Treatment of Knee Osteoarthritis

NCT ID: NCT04657926

Last Updated: 2021-11-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

152 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-09-09

Study Completion Date

2021-10-01

Brief Summary

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A placebo controlled study of APPA in 150 participants with Osteoarthritis of the knee

Detailed Description

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This is a multicenter, randomized, double-blind, placebo-controlled, parallel group, 4-week trial of a fixed-dose combination of apocynin and paeonol (APPA) administered orally twice daily versus placebo twice daily. Approximately 150 subjects will be randomized to one of the two treatment groups.

Conditions

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Osteoarthritis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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APPA

APPA, an oral combination of two isomers: 4-hydroxy-3-methoxyacetophenone (4H3MA) \& 2-hydroxy-4-methoxyacetophenone (2H4MA) administered to 75 participants as 2 x 400mg capsules b.d. for 28 days

.

Group Type EXPERIMENTAL

APPA

Intervention Type DRUG

APPA, an oral combination of two isomers: 4-hydroxy-3-methoxyacetophenone (4H3MA) \& 2-hydroxy-4-methoxyacetophenone (2H4MA).

Placebo

2 capsules b.d. for 28 days

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo capsules

Interventions

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APPA

APPA, an oral combination of two isomers: 4-hydroxy-3-methoxyacetophenone (4H3MA) \& 2-hydroxy-4-methoxyacetophenone (2H4MA).

Intervention Type DRUG

Placebo

Placebo capsules

Intervention Type DRUG

Eligibility Criteria

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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 (Altman et al., 1986) (Appendix A).
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 protocol specifications for 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 and baseline. The subject should have undergone a washout-period of at least 5 half-lives of any analgesic medication before completing the screening and baseline questionnaires.
6. Women of child-bearing potential must use a highly effective method of contraception(please see Appendix B). 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 ensure that their female partner uses a highly effective method of contraception and agree to use condom from enrolment up to at least 3 months after the study end. Furthermore, male participants must agree not to donate sperm throughout the study and at least 3 months after he 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. Inadequate response to or intolerance to analgesics and/or non-steroidal anti-inflammatory drugs (NSAIDs) as reported by the subject

Exclusion Criteria

1. Known or suspected hypersensitivity to or previous hypersensitivity reactions to APPA, or any of the excipients in the investigational product.
2. For women of childbearing potential:

1. Pregnancy (i.e. positive pregnancy test at Screening) or breastfeeding
2. Failure to agree to practice a highly effective method of contraception (see Appendix B), from enrolment up to at least 3 months after the study end.
3. For sexually active men with a female partner of childbearing potential: Failure to agree to ensure that their female partner uses a highly effective method of contraception, to agree to use condom (see Appendix B) from enrolment up to at least 3 months after the study end, and to agree not to donate sperm throughout the study and at least 3 months after the study end.
4. Intra-articular delivery of corticosteroids within 3 months or hyaluronic acid within 6 months of screening in the target knee or into any other joint within 30 days of screening.
5. Systemic corticosteroid treatment of more than 14 days during the past 6 months prior to screening.
6. Major surgery or arthroscopy of the target knee within the previous year prior to screening.
7. Planned surgery on either knee within the next 3 months.
8. Use of a currently unapproved investigational drug, device or biologic within 3 months prior to screening.
9. Presence of inflammatory arthritis, such as rheumatoid arthritis, psoriatic arthritis, polymyalgia rheumatica, gout or pseudogout with history of clinical attacks.
10. Current malignancy or treatment for malignancy within the past five years, with the exception of treated non-melanoma skin cancer, unless affecting the target knee area, or carcinoma in situ events.
11. Any other abnormal laboratory results or significant medical conditions that the Investigator believes should preclude the subject's participation in the trial.
12. Prior septic arthritis of the target knee.
13. 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 for that hip at the time of screening
14. Presence of significant radicular back pain, as reported by the subject.
15. 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 or baseline, regardless of the eligibility of the contralateral knee.
16. Body Mass Index \> 40.0 kg/m2.
17. Estimated glomerular filtration rate \< 30 mL/min using the Modification of Diet in Renal Disease (MDRD) method.
18. Substantial use of moderate or higher strength opioid medication for the treatment of pain within 6 weeks before the screening visit, as evaluated by the investigator.
19. Use of duloxetine, pregabalin, or gabapentin within 4 weeks before the baseline visit.
20. History of alcohol or drug abuse within the past 5 years prior to randomization.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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NBCD A/S

INDUSTRY

Sponsor Role collaborator

AKL Research and Development

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Asger Bihlet

Role: STUDY_DIRECTOR

Nordic Bioscience Clinical Development

Locations

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Sanos Clinic

Copenhagen, , Denmark

Site Status

Countries

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Denmark

References

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Yao Q, Wei T, Qiu H, Cai Y, Yuan L, Liu X, Li X. Epigenetic Effects of Natural Products in Inflammatory Diseases: Recent Findings. Phytother Res. 2025 Jan;39(1):90-137. doi: 10.1002/ptr.8364. Epub 2024 Nov 8.

Reference Type DERIVED
PMID: 39513382 (View on PubMed)

Other Identifiers

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APPA-P2-1

Identifier Type: -

Identifier Source: org_study_id