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Senolytic + Anti-Fibrotic Agents for Osteoarthritis

Phase 1 & 2

Waitlist Available

Led By Scott L Tashman, PhD

Research Sponsored by Steadman Philippon Research Institute

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Baseline pain of 3-10 points on the target knee and a pain differential of at least -2 points on the contralateral knee as exhibited by the worst pain score (on the 11-point Numeric Rating Scale) for the previous week.

Capacity to personally give informed consent (consent via legally authorized representative will not be accepted) and who are willing to comply with all study-related procedures and assessments

Must not have

Within 6 months of signing informed consent has undergone regenerative knee joint procedures including, but not limited to, platelet-rich plasma injections, mesenchymal stem cell transplantation, autologous chondrocyte transplantation, or mosaicplasty

Within 3 months of signing informed consent have taken senolytic agents including: Fisetin, Quercetin, Luteolin, Dasatinib, Piperlongumine, or Navitoclax

Timeline

Screening 3 weeks

Treatment Varies

Follow Up screening, 14 days post-injection, 30 days post injection, 3 months post injection, 6 months post injection, 12 months post injection

Summary

This trial is testing whether a senolytic agent (Fisetin) and an anti-fibrotic agent (Losartan), used independently or in combination, can improve the beneficial effect of an active control (injection of autologous bone marrow aspirate concentrate (BMAC) into an osteoarthritic knee).

Who is the study for?

This trial is for ambulatory adults aged 40-85 with osteoarthritis in at least one knee, experiencing a certain level of pain. They must be able to consent and follow the study procedures. Excluded are those taking Losartan or Fisetin, anticoagulants like Warfarin, have had recent knee surgery or injections, pregnant women, individuals unable to undergo an MRI, and those with various health conditions that could interfere with the study.

What is being tested?

The trial tests the safety and effectiveness of Fisetin (a senolytic agent) and Losartan (an anti-fibrotic agent), alone or combined, compared to bone marrow stem cell injections into the knee. It's randomized and double-blind meaning participants won't know which treatment they receive.

What are the potential side effects?

Potential side effects may include allergic reactions to Fisetin or Losartan ingredients; interactions with other medications; changes in blood pressure due to Losartan; gastrointestinal issues from either drug; fatigue; headaches; dizziness.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My knee pain scores between 3 to 10, and the other knee hurts 2 points less.

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I can understand and agree to the study's procedures on my own.

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I have knee osteoarthritis that affects my ability to move.

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I am between 40 and 85 years old.

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I can walk and have moderate to severe arthritis in my knee.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have had a knee regeneration procedure in the last 6 months.

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I have taken senolytic agents like Fisetin or Quercetin in the last 3 months.

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I have not taken senolytic agents like Fisetin or Dasatinib in the last 3 months, or I am willing to stop taking them for the study.

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I cannot take medicine by mouth.

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I am currently on Lithium medication.

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I haven't taken any medications that affect bone turnover in the last 12 months.

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I am a male willing to use contraception during the study.

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I am scheduled for knee surgery on the other or affected knee during the study.

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I have been diagnosed with diabetes according to the American Diabetes Association.

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I've had a knee injection with steroids or hyaluronic acid in the last 12 weeks.

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I am not pregnant, nursing, or planning to become pregnant during the study.

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I have been diagnosed with fibromyalgia.

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I have used opioid painkillers in the last 8 weeks and cannot stop during the study.

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I haven't had blood disorders or any cancer except skin cancer in the last 2 years.

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I am not taking, or willing to stop taking, drugs that cause significant cellular stress.

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I am currently on Warfarin or similar blood thinners.

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I am currently taking Losartan.

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I have taken opioid painkillers in the last 8 weeks and cannot stop during the study.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ screening, 14 days post-injection, 30 days post injection, 3 months post injection, 6 months post injection, 12 months post injection

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~screening, 14 days post-injection, 30 days post injection, 3 months post injection, 6 months post injection, 12 months post injection

This trial's timeline: 3 weeks for screening, Varies for treatment, and screening, 14 days post-injection, 30 days post injection, 3 months post injection, 6 months post injection, 12 months post injection for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Incidence of Treatment-Emergent Adverse Events

Secondary study objectives

Change in CTX-II as compared to placebo in urine

Change in associate biomarkers as compared to placebo in peripheral blood plasma/serum

Change in levels of senescent PBMCS (total and specific PBMC subsets such as T-Cells)

+16 more

Side effects data

From 2023 Phase 1 & 2 trial • 75 Patients • NCT04210986

38%

Arthralgia

15%

Pain in Extremity

12%

Lab Findings

12%

Nausea

Fatigue

Back Pain

Headache

Muscle Cramp

Flatulence

Dry Mouth

Rash Maculo-Papular

Covid 19

Bladder Perforation

Neoplasms

Rotator Cuff Injury

100%

80%

60%

40%

20%

Study treatment Arm

Placebo

Fisetin

Trial Design

4Treatment groups

Experimental Treatment

Active Control

Placebo Group

Group I: Active Fisetin and Active LosartanExperimental Treatment2 Interventions

Losartan 12.5 mg, PO, BID beginning the first day after BMA Concentrate injection and continuing for 30 days. Fisetin 20mg/kg taken a total of 4 days prior to BMA Concentrate injection (-32 and -31 and -3 and -2) then again after BMA Concentrate injection a for a total of 6 days (32 \& 33, 61 \& 62 and 90 \& 91).

Group II: Fisetin Placebo and Active LosartanActive Control2 Interventions

Losartan 12.5 mg, PO, BID beginning the first day after BMA Concentrate injection and continuing for 30 days. Fisetin Placebo 20mg/kg taken a total of 4 days prior to BMA Concentrate injection (-32 and -31 and -3 and -2) then again after BMA Concentrate injection a for a total of 6 days (32 \& 33, 61 \& 62 and 90 \& 91).

Group III: Active Fisetin and Losartan PlaceboActive Control2 Interventions

Losartan Placebo 12.5 mg, PO, BID beginning the first day after BMA Concentrate injection and continuing for 30 days. Fisetin 20mg/kg taken a total of 4 days prior to BMA Concentrate injection (-32 and -31 and -3 and -2) then again after BMA Concentrate injection a for a total of 6 days (32 \& 33, 61 \& 62 and 90 \& 91).

Group IV: ControlPlacebo Group2 Interventions

Losartan placebo 12.5 mg, PO, BID beginning the first day after BMA Concentrate injection and continuing for 30 days. Fisetin Placebo 20mg/kg taken a total of 4 days prior to BMA Concentrate injection (-32 and -31 and -3 and -2) then again after BMA Concentrate injection a for a total of 6 days (32 \& 33, 61 \& 62 and 90 \& 91).

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Fisetin

2016

Completed Phase 2

~250

Losartan

2003

Completed Phase 4

~3000