Biologic Therapy for Osteoarthritis Prevention After ACL Injury

Overseen By Adreanne Rivera

Age: 18 - 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of California, Los Angeles

Must not be taking: Cortisone, Anticoagulants, others

Disqualifiers: Multi-ligament injury, Infection, others

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

Duration: 3-5 days

32 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether Anakinra, a biologic therapy, can prevent osteoarthritis in individuals who have recently injured their ACL, a knee ligament. The researchers aim to determine if early Anakinra injections reduce future knee damage compared to a placebo. Individuals with an ACL injury confirmed by MRI within the last two weeks and planning ACL reconstruction surgery soon may qualify for this trial. Participants will receive two injections and will be monitored through surveys and MRI scans over two years to assess knee health and function. As an Early Phase 1 trial, this research focuses on understanding Anakinra's effects in people, offering participants the opportunity to be among the first to receive this treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are on anti-coagulation therapy or have had a cortisone injection in the knee within 3 months, you may not be eligible to participate.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that anakinra, a treatment tested to prevent arthritis after an ACL injury, is generally safe and well-tolerated. The main reported side effect is skin reactions at the injection site. Importantly, previous studies in people demonstrated that using anakinra in the knee is safe. It has even been used safely in individuals with existing knee arthritis. While minor side effects like skin irritation might occur, the treatment maintains a good safety record in similar situations. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for osteoarthritis, which often involve pain management or surgical interventions, anakinra offers a novel approach by addressing inflammation directly. Anakinra is unique because it is an interleukin-1 receptor antagonist, meaning it blocks a specific protein responsible for inflammation, which is a key factor in osteoarthritis development after an ACL injury. Researchers are excited about anakinra because it has the potential to prevent the onset of osteoarthritis rather than just managing symptoms, providing a proactive rather than reactive treatment option.

What evidence suggests that anakinra might be an effective treatment for preventing osteoarthritis after ACL injury?

Research has shown that anakinra, a medication that blocks certain proteins, may reduce knee pain and improve movement in people with ACL injuries. In this trial, some participants will receive two doses of anakinra after an ACL injury, before surgery. Studies have found that administering anakinra within the first month after a serious knee injury can lessen pain and improve knee function over two weeks. In animal studies, injecting this medication into the knee after an ACL injury significantly reduced arthritis later on. Anakinra blocks a protein called interleukin-1 (IL-1), which can cause swelling and damage to knee cartilage after an injury. The aim is to protect the cartilage and lower the risk of developing osteoarthritis in the future. ^{2 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for men and women aged 18-35 with a recent ACL injury who plan to have ACL reconstruction surgery within 45 days. They must not have severe knee injuries besides the ACL, no history of certain diseases or conditions, and no prior treatments that could interfere with the study.

Inclusion Criteria

My knee injury is minor.

I am between 18 and 35 years old and engage in sports that involve sudden direction changes.

I understand the trial seeks an equal number of men and women.

Exclusion Criteria

I have multiple torn ligaments in my knee.

My injury happened over 2 weeks ago.

You have had a bad reaction or allergy to anakinra in the past.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

1 visit (in-person)

Treatment

Participants receive two knee aspiration and injection procedures prior to surgery, with either saline or anakinra

3-5 days

2 visits (in-person)

Surgery

Participants undergo surgery for ACL injury, with additional arthrocentesis procedure performed

Within 45 days of injury

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including urine and synovial fluid analysis, MRI, and patient-reported outcomes

24 months

Multiple visits (in-person and virtual) at 3, 6, 9, 12, and 24 months

What Are the Treatments Tested in This Trial?

Interventions

• Anakinra

Trial Overview The trial tests if injecting Anakinra (a biologic therapy) into the knee after an ACL injury can prevent osteoarthritis. Participants are randomly placed in two groups: one gets Anakinra injections, while the other receives placebo saline injections before their surgery.

How Is the Trial Designed?

Group I: Two doses Anakinra Active Control 1 Intervention

Subjects will receive two injections of anakinra after ACL injury, prior to surgery

Group II: Control Placebo Group 1 Intervention

Subjects will receive two injections of sterile saline after ACL injury, prior to surgery

Anakinra is already approved in European Union, United States for the following indications:

Approved in European Union as Kineret for:

• Rheumatoid arthritis
• Cryopyrin-associated periodic syndromes
• Deficiency of interleukin-1 receptor antagonist
• COVID-19

Approved in United States as Kineret for:

• Rheumatoid arthritis
• Deficiency of interleukin-1 receptor antagonist
• Neonatal-onset multisystem inflammatory disease (NOMID)
• COVID-19

Who Is Running the Clinical Trial?

University of California, Los Angeles

Lead Sponsor

Trials

1,594

Recruited

10,430,000+

Orthopedic Research and Education Foundation

Collaborator

Trials

23

Recruited

6,200+

Published Research Related to This Trial

Anakinra (Kineret) is an effective treatment for rheumatoid arthritis that works by blocking the inflammatory effects of interleukin-1, but it requires daily self-injections due to its short half-life.

While Kineret is generally safe and well tolerated, it can cause injection-site reactions, which are common and may require management strategies to improve patient comfort.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Injection-site reactions upon Kineret (anakinra) administration: experiences and explanations. Kaiser, C., Knight, A., Nordström, D., et al.[2022]

A systematic review of 23 studies on biologic agents for ACL healing found that while platelet-rich plasma (PRP) is commonly used, its benefits are mainly limited to improved graft maturation rather than significant clinical outcomes or integration.

There is a lack of clinical trials on the use of stem cells for ACL healing, indicating a need for more research to understand their potential role in treating both partial and complete ACL tears.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biologic agents for anterior cruciate ligament healing: A systematic review. Di Matteo, B., Loibl, M., Andriolo, L., et al.[2020]

Citations

1. withpower.com withpower.com/trial/early-phase-1-osteoarthritis-4-2021-11836

Biologic Therapy for Osteoarthritis Prevention After ACL ... Anakinra (Kineret) is generally considered safe and well-tolerated in humans, with the main side effect being skin reactions at the injection site. These ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/22273632/

Effects of intraarticular IL1-Ra for acute anterior cruciate ... Conclusions: Administered within the first month following severe knee injury, IL-1Ra reduced knee pain and improved function over a 2-week interval. This ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02930122

IL-1RA Treatment in Patients With Acute ACL Tear and ... Often surgery can repair or replace the ACL within the joint, allowing individuals the ability to walk or run again pain free or participate in sports.

4. uclahealth.org uclahealth.org/clinical-trials/biologic-therapy-prevent-osteoarthritis-after-acl-injury

Biologic Therapy to Prevent Osteoarthritis After ACL Injury Early injection of IL-1 inhibitor (IL-1Ra) into the knee joint of patients suffering recent ACL injury will decrease the incidence of cartilage damage later in ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S106345841200012X

Effects of intraarticular IL1-Ra for acute anterior cruciate ... Administered within the first month following severe knee injury, IL-1Ra reduced knee pain and improved function over a 2-week interval.

6. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/258885

Biologic Therapy to Prevent Osteoarthritis After ACL Injury Unfortunately, ACL reconstruction does not prevent risk of future OA. Interleukin-1 (IL-1) levels in the human knee joint increase transiently ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3210259/

Emerging Ideas: Prevention of Posttraumatic Arthritis Through ... Preliminary data in a small pilot trial showed that intraarticular administration of a short acting IL-1 inhibitor, anakinra (Swedish Orphan Biovitrum Sverige ...

8. researchgate.net researchgate.net/profile/Alison-Toth/publication/273712803_Intra-articular_Anakinra_for_the_Treatment_of_Persistent_Inflammation_and_Arthrofibrosis_Following_Anterior_Cruciate_Ligament_Reconstruction/links/5534f3580cf2df9ea6a40a9f/Intra-articular-Anakinra-for-the-Treatment-of-Persistent-Inflammation-and-Arthrofibrosis-Following-Anterior-Cruciate-Ligament-Reconstruction.pdf

Intra-articular-Anakinra-for-the-Treatment-of-Persistent- ... 19-21 In addition, anakinra has been used safely via intra-articular administration in patients with established osteoarthritis of the knee.22. The senior ...