PFD iOI Announces Update On The iKnee Comfort Study And The Path Forward

Comfort Study Purpose

The PFD/iOI Comfort Study is designed to allow the company to gather critical data in three major areas:

1. The ability of the patient to tolerate the iKnee implant both from a bio-compatibility standpoint and an ortho-comfort level.
2. The ability of the iKnee implant to decrease or eliminate the patient’s pain level as it applies to the use of the impacted joint.
3. The ability of the iKnee to maintain or expand the patient’s quality of life as it pertains to daily activity, leisure and recreational movement, and/or active sports engagement.

Candidate Selection

Candidate selection for the study will be done by PFD/iOI’s Institutional Review Board (IRB) which is being sponsored and managed by Advarra, who is a global leader in supplying IRB, institutional bio-safety committee, and research compliance services to clinical trial sponsors, CROs, hospital systems, academic medical centers, and investigators. Candidates for the trial must meet the following criteria:

• Male or female above the age of 50
• Have a BMI of 30 or less.
• Have had a continual and chronic issue with their knee joint.
• Have a pre-operative Visual Analogue Pain Scale (VAS) score of ≥4
• Have failed all standard therapeutic care and treatment and are now candidates for a TKA.
• Be referred to the program by their Primary Care Physician (PCP) or by a qualified referring orthopedic specialist.
• Have no disqualifying health conditions or risks.

Once prospective candidates have submitted their applications, they are vetted by the PFD/iOI IRB for possible inclusion into the study. The application screening process consists of a series of steps to ensure that the candidate will be a viable cohort for the program and that there is an anticipated benefit to the patient’s knee issue and quality of life as a result of participation. The application review consists of an initial patient consult with a PFD/iOI-certified physician to include:

1. Initial patient background review.
2. Physical examination including a VAS and joint mobility assessment.
3. Initial consult on study overview, implantation procedure, and benefit/risk assessment.

Based on this evaluation, a request for medical records, copies of the latest radiological films, which can include X-rays, CAT and MRI scans, and any needed lab work is made. Once procured, an in-depth review of the applicant’s records, films, and labs is made by the qualified PFD/iOI surgeon along with the IRB. If at this point the applicant is deemed to be a viable cohort, a second consult is scheduled during which the study protocols and the implant procedure are once again thoroughly reviewed. If the applicant decides to move forward, a detailed Informed Consent document is signed along with any related additional release and medical information paperwork. Once processed the patient is given a case ID and a surgery date is scheduled.

The patient’s incision is then closed, and they are moved to post-op to recover from the anesthesia.

Once awake, a post-operative evaluation is made on the patient. Since the iKnee enables immediate weight-bearing, once cleared the patient is released to return home. The patient will have some limited post-op restrictions on use, but full recovery time is days rather than weeks or months as they would have had with a TKA.

Patient follow-up for the study is performed at 10 days, week six, week 12, and week 24 in order to assess the patient’s reaction to the iKnee. In these post-operative follow-ups, the patient is assessed for:

1. Comfort and level of pain
2. Joint mobility
3. Infection or inflammation
4. Evaluation of post-op imaging
5. Quality of life changes.

Comfort Study Post-Operative Follow-Up

The data is carefully recorded at each step and becomes part of the ongoing evaluation to ascertain several criteria including:

1. iKnee design for possible improvements.
2. Material integrity and bio-compatibility.
3. the ability of the implant to lower or eliminate joint pain.

Though the study is focused on the iKnee’s ability to provide comfort and relief for a minimum six-month period, PFD/iOI will continue to perform multi-year follow-ups with those cohorts who maintain their implants until such a time as they have a TKA procedure performed.

If, as expected, the initial FIH procedure is successful as defined by the study’s criteria of comfort, reduced pain, and bio-acceptance, enrollment of the next group of cohorts will begin immediately and evaluation and approval of other surgical centers across the US will proceed.

PFD/iOI Revenue Streams and the TKA Marketplace

PFD/iOI has stated its intention to not only be the manufacturer of the iKnee implant, as well as subsequent RAD applications, but also the managing authority for the physicians and centers where the implants will be performed. As such, PFD/iOI not only anticipates having a significant revenue stream from the modeling and manufacture of each custom implant, but also from each of the billable aspects of the Rev Share program. Billable services can include but are not limited to:

• Initial and follow-up patient consults
• Diagnosis or treatment of intra-articular joint pathology
• Third-party consults (PCP, Ortho specialist, Therapy provider, etc)
• Radiology scans
• Surgery center cost
• Surgeon and support cost (Anesthesiologist, OR nurse and care staff, etc.)
• Materials used in surgery.
• Various surgical procedures performed during the implant including:
  • Arthroscopy Knee Diagnostic
  • Osteochondral Autograft Arthroscopy
  • Arthroscopic Osteochondritis Dissecans Fragmentation Removal
  • Arthroscopic Chondral Fragmentation Removal
  • Arthroscopic Plica or Shelf Resection
  • Arthroscopic Major Synovectomy
  • Arthroscopic Knee Debridement
  • Arthroscopic Knee Abrasion arthroplasty (including drilling or micro-fracture)
  • Arthroscopic Knee Meniscectomy
  • Post-op therapy

With the current US TKA market sitting at $9.8 billion and the global TKA market set to grow by more than $2,408.49 million by 2027 with a CAGR of 22.15% and with 39% of that market being in the US , PFD/iOI anticipates it can capture a significant percentage of this expanding sector

IKNEE COMFORT STUDY

Description: the iKnee seeks to provide temporary comfort and improved function for patients awaiting total knee replacement arthroplasty (TKA). Reasons to delay a TKA include but are not limited to the need for weight loss, wound infection healing, implant availability, and required medical or psychological patient preparations. iKnee use determinations are made between the patient and caretaker. The subject population is individuals with refractory disabling knee pain who failed other conservative measures and are on track for TKA. The iKnee is to provide comfort, it is not intended to treat a disease, or underlying cause leading to TKA.

Objective: To study iKnee efficacy on quality of life and activities of daily living in patients awaiting TKA. The data will be used to improve possible designs to enhance patient comfort.

Procedure: A rolled polymer is inserted through a small parapatellar incision and then expanded to fit and pad the distal femur, providing a stable cushion made of medical polymers used safely and reliably for decades. The procedure is expected to take about 30 minutes, and involves an incision of 2-3 cm of subcutaneous tissue into the joint capsule, and an incision less than one cm in depth. The iKnee device is then inserted into the knee capsule. No muscles, tendons, or ligaments are cut.

Study Rationale: Total Knee Arthroplasty (TKA) has become one of the leading operations for senior citizens, both in cost and frequency. When a patient has a disabling knee condition limiting mobility and quality of life there is only one medical option, TKA. The TKA operation is a significant procedure, involving the removal of the bottom of the femur, the top of the tibia, and part of the patella to make space for the artificial metal and polyethylene prosthesis.

The study is designed to increase the patient’s quality of life, functionality, and comfort while they await the knee replacement operation (TKA). The iKnee procedure poses almost no medical risk to the patient, either as a procedure or as a risk to the patient’s knee as the decision has already been made to remove the joint.

INVESTIGATIONAL DEVICE EXEMPTION (IDE)

An investigational device exemption (IDE) allows the investigational device to be used in a clinical study to collect safety and effectiveness data. Clinical studies are most often conducted to support a PMA. Only a small percentage of 510(k)s require clinical data to support the application. Investigational use also includes clinical evaluation of certain modifications or new intended uses of legally marketed devices. All clinical evaluations of investigational devices, unless exempt, must have an approved IDE before the study is initiated.

Clinical evaluation of devices that have not been cleared for marketing requires:
an investigational plan approved by an institutional review board (IRB). If the study involves a significant risk device, the IDE must also be approved by FDA;

• informed consent from all patients;
• labeling stating that the device is for investigational use only;
• monitoring of the study and;
• required records and reports.

FIRST IN HUMAN (FIH)

A type of clinical trial in which a new drug, procedure, or treatment is tested in humans for the First time. Also called First-in-human study.
The following section is provided as a very basic tutorial on regulatory path and some of the terms, processes, and programs that new medical technologies must navigate to become commercial in the United States.

NON-SIGNIFICANT RISK

The FDA does not regulate Non-Significant Risk (NSR) devices.

The Sponsor has the responsibility of making a Significant Risk (SR) or NSR determination and may utilize the services of an IRB, though this is not required.

The RAD/iKnee device does not refer to curing any disease. We are implanting this minimally invasive device for a patient’s quality of life issues while they await a full TKA. This may be for comfort, mobility, or many other non-disease-related terms.

What is a Non-significant Risk Device Study?

NSR device studies must follow the abbreviated requirements at 21 CFR 812.2(b).

An IRB’s NSR determination is important because the IRB serves as the FDA’s surrogate for review, approval, and continuing review of the NSR device studies.

An NSR device study may start at the institution as soon as the IRB reviews and approves the study and without prior approval by FDA.

TITLE 21–FOOD AND DRUGS
CHAPTER I–FOOD AND DRUG ADMINISTRATION
DEPARTMENT OF HEALTH AND HUMAN SERVICES
SUBCHAPTER H – MEDICAL DEVICES

PART 812 — INVESTIGATIONAL DEVICE EXEMPTIONS

https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=812.2

FDA Pathways

FDA designation of the iKnee as an NSR Device. Pathways for commercialization are to be determined based on the commercialization path of the purchaser of IP.

Seven FDA Pathways to Bring a Medical Device to Market

 1.) Premarket Notification 510(k)

The Premarket Notification 510(k) pathway is the most common route taken when launching a medical device. Almost all Class II devices and certain Class I devices will require a 510(k).
The purpose of a 510(k) submission is to provide the FDA with documented evidence showing that a medical device is substantially equivalent in terms of safety and effectiveness to a predicate device.

A predicate device is one that is already legally marketed and shares the same intended use and technological characteristics as the new device. The requirement is to compare the new device with the predicate by summarizing information from the design controls process, such as design features and verification testing.

The FDA typically processes 510(k) applications in 30-90 days. Depending on the robustness of the initial application, there may be a period of back-and-forth discussions, which can delay the process. It is important to plan and provide all appropriate documentation at the time of initial submission.

2.) Premarket Approval (PMA)

Class III devices, and any device that cannot provide substantial equivalence to a Class I or Class II device through the 510(k) process, must use the Premarket Approval (PMA) pathway.

The PMA process is the most involved as scientific evidence, typically in the form of a clinical trial, is needed to prove the safety and effectiveness of the new device. The FDA will either approve or reject the application within 180 days. The different steps of the review process include:

• • • FDA staff will determine completeness through an administrative and limited scientific review
    • FDA staff will conduct an in-depth scientific, regulatory, and Quality System review
    • An advisory committee will review and offer any recommendations.
    • Any final deliberations will occur, and the FDA will document and notify the applicant of their final decision.

Although the premarket approval process sounds intimidating, it is the right option for a high-risk, Class III device.

3.) De Novo

If the applicant is developing a lower-risk, “novel” device and struggling to find a predicate, the De Novo pathway might be the best option.

The De Novo pathway has been around since 1997 but many people do not know about it since it is not very commonly used. Companies that do not qualify for 510(k) clearance, since they cannot provide substantial equivalence to a device on the market, should learn more about the De Novo pathway.

Since comparison to a predicate is not needed, companies have a “blank canvas” when it comes to labeling and can set a standard that may give them a competitive advantage over others. One of the key things to remember about the De Novo pathway is that the device must present low to moderate risk through a robust risk mitigation strategy.

4.) Humanitarian Device Exemption (HDE)

The Humanitarian Device Exemption (HDE) pathway is for devices that are intended to treat or diagnose conditions or diseases that affect small or rare populations.

This pathway involves a two-step process. The FDA must grant a Humanitarian Use Device (HUD) exemption and the device company must then submit an HDE application to the appropriate review center.

Another important requirement is that there cannot be another comparable device on the market that shares the same intended use. The FDA will consider the following when determining if there are comparable devices on the market:

• • • The device’s indications for use and technological characteristics.
    • The patient population to be treated or diagnosed with the device.
    • Whether the device meets the needs of the identified patient population.

Part of the rationale for providing this pathway is there may not be a large enough patient population with clinical data to satisfy regular FDA requirements of safety and efficacy. Since these devices may be very crucial to patients with rare conditions, the FDA put them in place to do a proper review to determine if the device can be sold.

5.) Custom Device Exemption (CDE)

Is the company developing a custom device for a specific patient? If so, the device falls under the Custom Device Exemption (CDE) pathway and must meet a very narrow set of criteria.
The device must be created or modified to comply with the order of an individual physician or dentist, typically in the form of a prescription. Not only must the clinician order the device, but it must also be used in the normal course of the professional practice of that physician or dentist.

The product should be specifically designed to treat a unique pathology or physiological condition that no other device is domestically available to treat. It must be assembled from components or manufactured and finished on a case-by-case basis to accommodate the unique needs of the patient.

The FDA even states that companies are limited to no more than 5 units per year of a particular device type.

CDE devices are exempt from PMA or 510(k) submission process, but the company still needs to comply with the following regulations:

• • • Design Controls (21 CFR Part 820)
    • Medical Device Reporting (21 CFR Part 803)
    • Labeling (21 CFR Part 801)
    • Corrections and Removals (21 CFR Part 806)
    • Registration and Listing (21 CFR Part 807)

6.) Expanded Access Program (EAP)

The Expanded Access Program, often referred to as the compassionate use or emergency use provision, is fairly self-explanatory.

It allows an investigational device to be used, outside of a clinical trial, in situations where a seriously ill patient has few if any alternatives.

Although there are often ethical considerations, it may be appropriate to evaluate this option to get early feasibility data for high-risk devices, especially when suitable animal models are unavailable. Like the HDE, this data could then be used to expand the label in the future.

• • • Expanded access may be an appropriate pathway for you to choose when all the following apply:
    • Patient has a serious disease or condition, or whose life is immediately threatened by their disease or condition.
    • There is no comparable or satisfactory alternative therapy to diagnose, monitor, or treat the disease or condition.
    • Patient enrollment in a clinical trial is not possible.
    • Potential patient benefit justifies the potential risks of treatment. • Providing the investigational medical product will not interfere with investigational trials that could support a medical product’s development or marketing approval for the treatment indication.

7.) Product Development Protocol (PDP)

The Product Development Protocol (PDP) is a subset of the PMA process that allows for another pathway for companies with devices in which the technology is well established in the industry.

This pathway allows the company to come to an early agreement with the FDA about how the safety and effectiveness of the device will be shown. The two parties are essentially creating a contract that describes design and development activities, including the outputs of these activities, and acceptance criteria for these outputs.

The company can follow the plan on its own time and report back to the FDA on the agreed-upon milestones. At the end of the process, the company is considered to have “completed” a PDP, which gives them an “approved” PMA.

A managing sponsor of fundraising efforts for the affiliated companies of the PFD family of companies,