Feasibility of the Artimis*medial meniscus prosthesis intended to restore the medial meniscus function to provide pain relief after meniscectomy

Meniscal tears are the most common knee injury, resulting in approximately 61
meniscectomies per 100,000 patients annually [1]. In the Netherlands, in 2010,
approximately 42,000 meniscectomies were performed annually and, in the US,
approximately 500,000 patients are subject to partial or total meniscectomy.
Meniscectomy results in impaired function of the meniscus and decreases the
contact area by up to 75% and increase contact pressures by up to 300% [2].
Clinical and radiological studies have shown that most patients improve
clinically post-meniscectomy, but that partial or complete loss of the meniscus
promotes in 40% of the post-meniscectomy patients the early development and
progression of Knee Osteoarthritis (KOA) 5-20 years post-surgery [3]. KOA is a
chronic joint disease that results from breakdown of joint cartilage and the
underlying bone. The most common symptoms of KOA are chronic joint pain,
stiffness and swelling of the knee. Chatain, et al. [4] outlines that 14% of
these post-meniscectomy patients demonstrates the rapid onset of symptomatic
unicompartmental pain in the meniscus-deficient knee, the so-called
post-meniscectomy pain syndrome.

As no cure for the post-meniscectomy pain syndrome patient is currently
available, most patients endure the remaining pain and experience gradual loss
of their mobility. Therefore, patients have to adapt their daily life
activities. The disease symptoms often have a profound effect on the quality of
life (QoL), affecting both physical functioning and psychological parameters.
There are no specific clinical guidelines for the post-meniscectomy pain
syndrome and therefore these patients suit best in the osteoarthritis
guidelines and are treated likewise. In these knee osteoarthritis guidelines
[5] the Standard of Care (SOC) treatment scheme is as follows:
• First line of treatment is a combination of non-pharmacological interventions
such as exercise, education and weight loss programs, physical therapy and use
of assistive devices. During this stage of the disease, physicians often
recommend soft pain medication, such as paracetamol.
• Second line of treatment involves stronger pain medication, such as
nonsteroidal anti-inflammatory drugs (NSAIDs) and the even less-desirable
opioids. Also, corticosteroid injections are applied directly into the knee
joint. These treatments reduce pain but do not prevent continuous joint
degeneration. This will eventually result in a more severe KOA, for which
pharmacological pain intervention is no longer sufficient. With a mean age at
KOA diagnosis of 54 years-old, the average time on pain medication preceding
the third line of treatment is 13 years for the regular patient (K/L grade 2)
[8].
• Third line and final treatment: once most articular cartilage is degenerated
and first- and second-line conservative therapies are no longer effective to
delay or prevent disease progression, surgical treatment is often necessary.
The SOC surgical treatment for end-stage KOA is Total Knee Arthroplasty (TKA)
or Unicompartmental Knee Arthroplasty (UKA). This highly invasive surgical
intervention removes the diseased bone and cartilage from respectively one or
both knee joint compartments, which is replaced with an artificial joint made
of synthetic materials. TKA have demonstrated improved function, reduced pain
and improved QoL for patients [9]. For ease of reading, TKA and UKA are grouped
as *TKA* in the remainder of this document, unless specifically indicated
separately. A distinct limitation of TKA is that it is a suboptimal treatment
option in patients under the age of 65 years since younger active and
high-demand patients are at a greater risk for prosthesis failure due to
reduced durability of the TKA. Consequently, the patients are likely to outlive
their prosthesis and a revision surgery is required to replace the original
implant with a new knee replacement. This is a more complex procedure
associated with higher complication rates, extended hospitalization, and
unsatisfactory functional outcomes [10]. After the revision TKA no other
treatment options are possible, leaving the patient immobile and wheelchair
bound when the prosthesis stops functioning.

The development of the Artimis*medial meniscus prosthesis focuses on those
post-meniscectomy pain syndrome patients, with limited underlying cartilage
damage (Kellgren Lawrence scale 0-3), who remain with unicompartmental pain in
the medial meniscus-deficient knee and reduced mobility. This is the patient
group that spend on average 13 years on a non-surgical regimen of pain
medication [8]. Treatment options for patients with meniscus deficient knees
are limited to transient conservative treatment options (i.e., first and second
line of treatment of SOC). This treatment often falls short, and the pain
remains on an unacceptable level in many patients. Furthermore, in a meniscus
deficient knee the KOA progresses till it reaches end-stage KOA condition, then
the only solution is a TKA whereby the degenerative (part of the) joint is
removed and replaced. There is a large treatment gap between the first knee
pain after meniscectomy and the eligibility for a TKA. Hence, there is a strong
unmet need for a durable and cost-effective treatment solution that will
relieve chronic knee pain and regain mobility in symptomatic post-meniscectomy
patients. Such treatment could save the knee joint and delay or prevent the
need for a knee joint replacement.

The Artimis* medial meniscus prosthesis is intended to restore the function of
the natural meniscus to provide unicompartmental pain relief in the
meniscus-deficient knee. The Artimis* medial meniscus prosthesis is intended to
restore the function of the natural meniscus and redistributes the loads
transmitted across the knee joint.

The objective of the clinical investigation is to evaluate the safety and
performance of the Artimis* medial meniscus prosthesis system and to
demonstrate that the Artimis* medial meniscus prosthesis is able to restore the
function of the natural meniscus to provide pain relief in the medial
compartment of the meniscus-deficient knee.

This is a prospective, multi-center, open label, single arm clinical
investigation.

The implantation of the meniscus prosthesis and fixation tape and anchoring
screws is conducted by means of an arthroscopic procedure, minimizing the
surgical damage to the joint. A regular arthroscopic inspection is performed
through two portals in the skin and capsule on the anterior side of the knee.
The lateral portal provides access for the camera and the medial portal for the
surgical instruments. The surgical technique is described in CIP section 2.9.

The present clinical investigation represents the second prospective clinical
evaluation in humans of the Artimis* medial meniscus prosthesis. The first
design of the Artimis* medial meniscus prosthesis has been evaluated in a
previous feasibility (First in Man, AIR clinical investigation, AM-001)
clinical investigation, which has been prematurely stopped due to the
occurrence of serious adverse device effects. Based on the learnings from this
clinical investigation, ATRO Medical has improved the design of the Artimis*
medial meniscus prosthesis and confirmed the functionality of the device by
extensive in-vitro testing. ATRO Medical can confirm that any potential risk
presented by this clinical investigation has been minimized by in-vitro
testing, appropriate product design and through use training. ATRO Medical can
confirm that any potential risk presented by this clinical investigation has
been minimized by in-vitro testing, appropriate product design and through use
training. Based on this data, we anticipate the clinical benefit of the
Artimis* medial meniscus prosthesis may include:
• Pain relief in the medial compartment of the knee
• Increased functional activity
• Symptom relief
• Improved Quality of Life

The following potential Anticipated Adverse Device Effects (AADEs) may arise as
a result of implanting the investigational device:
• Pain discomfort and/or Range of Motion (RoM) impairment, caused by
oversizing, undersizing or wrong placement of the meniscus prosthesis
• Pain discomfort and/or RoM impairment, caused by impingement of the meniscus
prosthesis
• Breakage of the meniscus prosthesis, potentially leading to pain discomfort
and requiring consecutive surgery to remove or replace the prosthesis
• Wear of the meniscus prosthesis, potentially leading to breakage, pain
discomfort and/or synovitis
• Wear of the TLS® tape, potentially leading to breakage and/or synovitis
• Post-operative infection of the joint, which requires consecutive surgery
with rinsing of the joint and longtime antibiotics, and possible removal of the
implant. This may cause damage to the knee joint structures and tissues.
• Neurovascular damage during the procedure: The drilling of the posterior
drill hole may damage the neurovascular structures posterior in the knee
(popliteal nerve, artery and vein)