A Trial of APPA in the Treatment of Knee Osteoarthritis

NCT04657926 | Completed Phase 2 DMC

• 1 other identifier: APPA-P2-1
• Study Type: interventional
• Target: 152
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Osteoarthritis

Outcome Measures

Primary Outcomes (1)

• WOMAC pain score

  change from baseline in WOMAC pain sub-score of the target knee as evaluated at week 4.

  28 days

Secondary Outcomes (12)

• Changes from baseline in WOMAC total score and the WOMAC function and stiffness scores at week 4

  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

  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

  28 days

• Changes from baseline in physical function assessed by the 20 Meter Walk Test gait speed at week 4

  28 days

• Change from baseline in the weekly mean of the average daily pain intensity at Week 4

  28 days

Other Outcomes (3)

• Changes in serum and urine biomarkers of joint tissue turnover

  28 days

• Time to achieve a clinically relevant pain reduction defined as a decrease from baseline of at least 1 points out of 10 in the 11-point average of daily pain score

  28 days

• Time to achieve "moderate improvement" and time to achieve "high improvement" in OMERACT-OARSI response

  28 days

Study Arms (2)

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 .

Drug: APPA

Placebo

PLACEBO COMPARATOR

2 capsules b.d. for 28 days

Drug: Placebo

Interventions

APPA DRUG

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

APPA

Placebo DRUG

Placebo capsules

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• AKL Research and Development: lead
• NBCD A/S: collaborator

Study Sites (1)

Sanos Clinic

Copenhagen, Denmark

Location

Related Publications (1)

• 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.

  PMID: 39513382 DERIVED

MeSH Terms

Conditions

Osteoarthritis

Interventions

diadenosine pyrophosphate

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Study Officials

• Asger Bihlet

  Nordic Bioscience Clinical Development

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 30, 2020
• First Posted: December 8, 2020
• Study Start: September 9, 2020
• Primary Completion: September 30, 2021
• Study Completion: October 1, 2021
• Last Updated: November 17, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)