Senolytic Drugs Attenuate Osteoarthritis-Related Articular Cartilage Degeneration: A Clinical Trial

NCT04210986 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 2019-16
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

Phase I/II randomized, double-blind, placebo-controlled clinical trial to test the safety and efficacy of Fisetin for treating mild to moderate osteoarthritis

Conditions

Osteoarthritis, Knee

Keywords

Fisetin; Inflammation; Osteoarthritis

Outcome Measures

Primary Outcomes (1)

• Number of Participants Experiencing One or More Treatment-Emergent Adverse Event

  Number of Participants Experiencing one or more Treatment-Emergent Adverse Event (TEAE) within each group.

  Duration of study, an average of 12 months

Secondary Outcomes (12)

• Change in Levels of Pro-inflammatory Markers Associated With Senescence

  14 days, 45 days, 6 months, 12 months (post 1st drug dose)

• Change in Levels of Cartilage Degenerating Markers Associated With OA

  14 days, 45 days, 6 months, 12 months (post 1st drug dose)

• Change in Physical Function of the Study Knee (6 Min Walk)

  6 months, and 12 months (post 1st drug dose)

• Change in Physical Function of the Study Knee (Timed-up-and-go Test)

  6 months, and 12 months (post 1st drug dose)

• Change in Physical Function of the Study Knee (Fast 4-meter Walk)

  6 months, and 12 months (post 1st drug dose)

Study Arms (2)

Fisetin

EXPERIMENTAL

Fisetin 100 mg capsules (\~20 mg/ kg/ day) will be administered orally for two consecutive days (days 1 and 2) followed by 28 days off. A second course will be given for two consecutive days (days 31 and 32)

Dietary Supplement: Fisetin

Placebo

PLACEBO COMPARATOR

Placebo capsules will be administered orally for two consecutive days (days 1 and 2) followed by 28 days off. A second course will be given for two consecutive days (days 31 and 32)

Drug: Placebo oral capsule

Interventions

Fisetin DIETARY_SUPPLEMENT

Fisetin will be administered orally at 20 mg/kg for two consecutive days, followed by 28 days off, then 2 more consecutive days.

Also known as: Novusetin, 7,3',4'-flavon-3-ol, 3,3',4',7-tetrahydroxyflavone

Fisetin

Placebo oral capsule DRUG

Placebo will be administered orally for two consecutive days, followed by 28 days off, then 2 more consecutive days.

Also known as: Inactive drug

Placebo

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects will be included if all the following criteria are met:
• Are male or female, ages 40-80;
• Are willing to comply with all study related procedures and assessments;
• Are ambulatory as defined by ability to complete functional performance testing;
• Radiographic evidence of Kellgren-Lawrence grade II-IV osteoarthritis in one or both knees;
• Scores 4-10 on the Numerical Rating Scale (NRS) for pain;
• Stable dose of screening/baseline medications for at least 2 months prior to the anticipated date of study drug dosing.

You may not qualify if:

• Subjects will be excluded if any of the following criteria are met:
• Females who are nursing, pregnant or planning to become pregnant during the duration of study drug dosing;
• Males who do not wish to abstain from sex or use contraceptive protection during study drug dosing and for 2 weeks after the last dose;
• Subjects who do not have the capacity to consent themselves;
• Subjects who are unable to tolerate oral medication;
• Subjects having previously undergone any of the following treatments in the stated time window.
• Surgery on the Study Knee in the past 6 months;
• Partial or complete joint replacement in the study knee. Partial or complete joint replacement in the contralateral knee is acceptable as long as the surgery was performed at least 6 months prior to enrollment and the operative knee is asymptomatic;
• Patients who have undergone arthroscopic surgery (including microfracture and meniscectomy) on the Study Knee in the last 2 years prior to the Screening visit or are anticipated to have arthroscopic surgery on either knee at any time during the study period;
• Steroid injection, including extended-release corticosteroid (e.g., Zilretta®) within the last 5 months;
• Biologic (platelet-rich plasma, bone marrow, adipose tissue/cells) or hyaluronic acid injection into the Study Knee in the past 6 months;
• Subjects with any of the following drug/medication statuses:
• Currently taking Losartan;
• Currently taking Warfarin or related anticoagulants;
• Opioid analgesics taken in the past 8 weeks and are not willing to discontinue these medications through the duration of the study;

Sponsors & Collaborators

• Steadman Philippon Research Institute: lead
• United States Department of Defense: collaborator
• Office of Naval Research (ONR): collaborator

Study Sites (1)

The Steadman Clinic

Vail, Colorado, 81657, United States

Location

MeSH Terms

Conditions

Osteoarthritis, Knee; Inflammation; Osteoarthritis

Interventions

fisetin

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Suzanne Liv Page
• Organization: Vice President of Operations

spage@sprivail.org

970-401-8770

Study Officials

• Thomas A Evans, MD

  The Steadman Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 3, 2019
• First Posted: December 26, 2019
• Study Start: January 6, 2020
• Primary Completion: January 5, 2023
• Study Completion: February 1, 2023
• Last Updated: September 19, 2024
• Results First Posted: September 19, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)