OsteoarthritisPhase 2NCT04657926
A Trial of APPA in the Treatment of Knee Osteoarthritis
A Phase 2 study testing APPA in people with Osteoarthritis, run by AKL Research and Development at 1 site in Denmark.
Trial summary
A placebo controlled study of APPA in 150 participants with Osteoarthritis of the knee Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Osteoarthritis
- What is being tested?
- APPA
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 152 participants
- Where
- 1 siteDenmark
- Study dates
- 9 Sep 2020to 1 Oct 2021
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- Femorotibial osteoarthritis of the knee, according the American College of Rheumatology (ACR) clinical and radiographic criteria (Altman et al., 1986) (Appendix A).
- 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.
- Age between 40 years and 85 years at the time of screening, both included; of either sex.
- 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.
- 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.
- 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.
- Inadequate response to or intolerance to analgesics and/or non-steroidal anti-inflammatory drugs (NSAIDs) as reported by the subject
Who cannot join
- Known or suspected hypersensitivity to or previous hypersensitivity reactions to APPA, or any of the excipients in the investigational product.
- For women of childbearing potential:
- Pregnancy (i.e. positive pregnancy test at Screening) or breastfeeding
- 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.
- 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.
- 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.
Show all 22Show fewer
- Systemic corticosteroid treatment of more than 14 days during the past 6 months prior to screening.
- Major surgery or arthroscopy of the target knee within the previous year prior to screening.
- Planned surgery on either knee within the next 3 months.
- Use of a currently unapproved investigational drug, device or biologic within 3 months prior to screening.
- Presence of inflammatory arthritis, such as rheumatoid arthritis, psoriatic arthritis, polymyalgia rheumatica, gout or pseudogout with history of clinical attacks.
- 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.
- Any other abnormal laboratory results or significant medical conditions that the Investigator believes should preclude the subject's participation in the trial.
- Prior septic arthritis of the target knee.
- 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
- Presence of significant radicular back pain, as reported by the subject.
- 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.
- Body Mass Index > 40.0 kg/m2.
- Estimated glomerular filtration rate < 30 mL/min using the Modification of Diet in Renal Disease (MDRD) method.
- 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.
- Use of duloxetine, pregabalin, or gabapentin within 4 weeks before the baseline visit.
- History of alcohol or drug abuse within the past 5 years prior to randomization.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Placebo-controlled, Double-blinded, Randomized, Trial Using a Combination of Apocynin and Paeonol (APPA) for the Treatment of Knee Osteoarthritis
A placebo controlled study of APPA in 150 participants with Osteoarthritis of the knee
Read the detailed description
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
- Osteoarthritis
- Being tested
- APPA, Placebo
- Medical subject headings
- Osteoarthritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
APPADrug
APPA, an oral combination of two isomers: 4-hydroxy-3-methoxyacetophenone (4H3MA) \& 2-hydroxy-4-methoxyacetophenone (2H4MA).
PlaceboDrug
Placebo capsules
| Study group | Role | What they receive |
|---|---|---|
| APPA | Experimental | 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
. Receives: Drug: APPA |
| Placebo | Placebo comparator | 2 capsules b.d. for 28 days Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
WOMAC pain score
change from baseline in WOMAC pain sub-score of the target knee as evaluated at week 4.
Measured: 28 days
Secondary outcomes (12)
Changes from baseline in WOMAC total score and the WOMAC function and stiffness scores at week 4
Measured: 28 days
Changes from baseline in constant, intermittent and total OA pain assessed by ICOAP scores at week 4 Changes from baseline in constant, intermittent and total OA pain assessed by ICOAP scores at week 4
Measured: 28 days
Changes from baseline in WOMAC pain weight-bearing score (questions 1, 2, and 5) and non-weight bearing score (questions 3 and 4) at week 4
Measured: 28 days
Changes from baseline in physical function assessed by the 20 Meter Walk Test gait speed at week 4
Measured: 28 days
Change from baseline in the weekly mean of the average daily pain intensity at Week 4
Measured: 28 days
Area-under-effect curves of the weekly mean of the average daily pain intensity at Week 4
Measured: 28 days
OMERACT-OARSI responder rate at week 4
Measured: 28 days
Total dose of rescue medication calculated as the sum of tablets used, based on pill counts
Measured: 28 days
Time between baseline and first use of rescue medication
Measured: 28 days
Changes from baseline in the Patient Global Assessment (PGA) score at week 4
Measured: 28 days
Changes from baseline in quality of life assessed by the EQ5D at week 4
Measured: 28 days
Safety
Nature, incidence and severity of AEs. Changes in laboratory safety parameters, vital signs, 12-lead ECG parameters, and weight
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Dec 2020
- Study start9 Sep 2020
- Primary completion30 Sep 2021
- Study completion1 Oct 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for OsteoarthritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 152 participants (actual)
Sponsor and investigators
- Lead sponsor
- AKL Research and Development
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- NBCD A/S
- Responsible party
- Sponsor
- Investigators
- Asger Bihlet, Study director, Nordic Bioscience Clinical Development
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04657926
- Sponsor's protocol ID
- APPA-P2-1
- Status last verified
- Nov 2021
- First submitted
- 30 Nov 2020
- Last updated
- 17 Nov 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 39513382
Study at a glance
From the registry record, last updated by the sponsor on 17 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Placebo-controlled, Double-blinded, Randomized, Trial Using a Combination of Apocynin and Paeonol (APPA) for the Treatment of Knee Osteoarthritis
- ClinicalTrials.gov ID
- NCT04657926
- Acronym / sponsor ID
- APPA-P2-1
- Conditions
- Osteoarthritis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 152 participants (actual)
- Lead sponsor
- AKL Research and DevelopmentIndustry (pharma, biotech, devices)
- Collaborators
- NBCD A/S
- Study start
- 9 Sep 2020 (actual)
- Primary completion
- 30 Sep 2021 (actual)
- Study completion
- 1 Oct 2021 (actual)
- First posted
- 8 Dec 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A placebo controlled study of APPA in 150 participants with Osteoarthritis of the knee
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| APPA | Experimental | Drug: APPAAPPA, 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 . |
| Placebo | Placebo comparator | Drug: Placebo2 capsules b.d. for 28 days |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
- Femorotibial osteoarthritis of the knee, according the American College of Rheumatology (ACR) clinical and radiographic criteria (Altman et al., 1986) (Appendix A).
- 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.
- Age between 40 years and 85 years at the time of screening, both included; of either sex.
- 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.
Key exclusion criteria (22 listed)
- Known or suspected hypersensitivity to or previous hypersensitivity reactions to APPA, or any of the excipients in the investigational product.
- For women of childbearing potential:
- 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.
- 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.
- Systemic corticosteroid treatment of more than 14 days during the past 6 months prior to screening.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| APPAAPPA, an oral combination of two isomers: 4-hydroxy-3-methoxyacetophenone (4H3MA) \& 2-hydroxy-4-methoxyacetophenone (2H4MA). | Drug | APPA |
| PlaceboPlacebo capsules | Drug | Placebo |
Primary outcome
WOMAC pain score
Time frame: 28 days
change from baseline in WOMAC pain sub-score of the target knee as evaluated at week 4.
12 secondary outcomes
Changes from baseline in WOMAC total score and the WOMAC function and stiffness scores at week 4
Time frame: 28 days
Changes from baseline in constant, intermittent and total OA pain assessed by ICOAP scores at week 4 Changes from baseline in constant, intermittent and total OA pain assessed by ICOAP scores at week 4
Time frame: 28 days
Changes from baseline in WOMAC pain weight-bearing score (questions 1, 2, and 5) and non-weight bearing score (questions 3 and 4) at week 4
Time frame: 28 days
Changes from baseline in physical function assessed by the 20 Meter Walk Test gait speed at week 4
Time frame: 28 days
Change from baseline in the weekly mean of the average daily pain intensity at Week 4
Time frame: 28 days
Area-under-effect curves of the weekly mean of the average daily pain intensity at Week 4
Time frame: 28 days
OMERACT-OARSI responder rate at week 4
Time frame: 28 days
Total dose of rescue medication calculated as the sum of tablets used, based on pill counts
Time frame: 28 days
Time between baseline and first use of rescue medication
Time frame: 28 days
Changes from baseline in the Patient Global Assessment (PGA) score at week 4
Time frame: 28 days
Changes from baseline in quality of life assessed by the EQ5D at week 4
Time frame: 28 days
Safety
Time frame: 28 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Nov 2021.
- Derived from this study: PubMed 39513382Yao 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Asger Bihlet study director
Nordic Bioscience Clinical Development
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing APPA in people with Osteoarthritis, run by AKL Research and Development at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
WOMAC pain score (time frame: 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04657926, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Nov 2021.