آلوگرافت عصبی پردازش شده

AVANCE یک داربست عصبی بدون سلول است که برای درمان بیماران بزرگسال و کودکان یک ماهه و بالاتر با موارد زیر نشان داده شده است:

• ناپیوستگی عصب حسی (≤25 میلی متر). (1)
• ناپیوستگی عصب حسی (بیش از 25 میلی متر). این اندیکاسیون تحت تأیید تسریع شده بر اساس تمایز دو نقطه ای استاتیک (s2PD) در 12 ماه در شکاف های عصبی حسی ≤25 میلی متر تأیید شده است، که شواهد تجربی برای پیش بینی منطقی مزایای بالینی با توجه به شباهت ها در پاتوفیزیولوژی و اثرات درمانی پیش بینی شده ارائه می دهد. ادامه تأیید برای این نشانه ممکن است منوط به تأیید و شرح مزایای بالینی در یک کارآزمایی بالینی تأییدی باشد. ( 1 , 14 )
• ناپیوستگی عصب مخلوط و حرکتی. این اندیکاسیون تحت تأیید تسریع شده بر اساس s2PD در 12 ماه در شکاف‌های عصبی حسی تأیید می‌شود، که شواهد تجربی برای پیش‌بینی منطقی سود بالینی با توجه به شباهت‌ها در پاتوفیزیولوژی و اثرات درمانی پیش‌بینی‌شده ارائه می‌دهد. ادامه تأیید برای این نشانه ممکن است منوط به تأیید و شرح مزایای بالینی در یک کارآزمایی بالینی تأییدی باشد. ( 1 , 14 )

1.1 ناپیوستگی عصب حسی (≤25 میلی متر) AVANCE برای درمان بیماران بزرگسال و کودکان یک ماهه و بالاتر با ناپیوستگی عصب حسی ≤25 میلی متر نشان داده شده است.

1.2 ناپیوستگی عصبی حسی (بیش از 25 میلی متر) AVANCE برای درمان بیماران بزرگسال و کودکان یک ماهه و بالاتر با ناپیوستگی اعصاب حسی محیطی > 25 میلی متر نشان داده شده است. این اندیکاسیون تحت تایید تسریع شده بر اساس بهبود در تشخیص دو نقطه ای استاتیک (s2PD) در 12 ماه در شکاف های عصب حسی ≤ 25 میلی متر تایید شده است، که شواهد تجربی را برای پیش بینی منطقی سود بالینی با توجه به شباهت ها در پاتوفیزیولوژی و اثرات درمانی پیش بینی شده ارائه می کند. [به مطالعات بالینی (14) مراجعه کنید]. ادامه تأیید برای این نشانه ممکن است منوط به تأیید و شرح مزایای بالینی در کارآزمایی‌های بالینی تأییدی باشد.

1.3 ناپیوستگی اعصاب مختلط و حرکتی AVANCE برای درمان بیماران بزرگسال و کودکان یک ماهه به بالا با ناپیوستگی عصب مختلط و حرکتی نشان داده شده است. این اندیکاسیون تحت تایید تسریع شده بر اساس بهبود s2PD در 12 ماه در شکاف‌های عصب حسی، که شواهد تجربی را برای پیش‌بینی معقول سود بالینی با توجه به شباهت‌ها در پاتوفیزیولوژی و اثرات درمانی پیش‌بینی‌شده ارائه می‌دهد، تایید شده است. [به مطالعات بالینی (14) مراجعه کنید]. ادامه تأیید برای این نشانه ممکن است منوط به تأیید و شرح مزایای بالینی در یک کارآزمایی بالینی تأییدی باشد.

رنگ AVANCE از سفید، مایل به سفید، صورتی، صورتی کم رنگ و زرد تا زرد کم رنگ متفاوت است. AVANCE یک ایمپلنت استریل و جراحی است و برای تزریق به یک بیمار در نظر گرفته شده است. اندازه های موجود AVANCE در جدول 1 ارائه شده است. AVANCE در 16 سایز ترکیبی با ابعاد زیر موجود است:

• طول: 15 میلی متر، 30 میلی متر، 50 میلی متر و 70 میلی متر
• قطرها: 1 تا 2 میلی متر، 2 تا 3 میلی متر، 3 تا 4 میلی متر و 4 تا 5 میلی متر AVANCE ممکن است از نظر رنگ از سفید، سفید، صورتی، صورتی کم رنگ و زرد تا زرد کم رنگ متفاوت باشد. (3)

هیچ کدام هیچ کدام (4)

5 WARNINGS AND PRECAUTIONS

• Procedural Complications – Monitor for procedural complications, including pain, hyperesthesia, infection, implant site swelling, adhesions, hypertrophic scar formation, impaired motor or sensory function, bleeding, and neuroma formation, and manage accordingly. ( 5.1 )
• Transmission of Infectious Diseases – Because AVANCE is made from human donor tissue, it may carry a risk of transmitting infectious agents, e.g., viruses, the variant Creutzfeldt-Jakob disease (vCJD) agent, and theoretically, the Creutzfeldt-Jakob disease (CJD) agent. No cases of transmission of viral diseases, vCJD, or CJD have ever been identified for AVANCE. All infections thought to be transmitted by AVANCE should be reported to Axogen Corporation at 1-888-296-4361. ( 5.2 )

5.1 Procedural Complications Procedural complications have occurred with the AVANCE implantation procedure and have included pain, hyperesthesia, infection, implant site swelling, adhesions, hypertrophic scar formation, impaired motor or sensory function, bleeding, and neuroma formation [see Adverse Reactions ( 6 )] . Additional procedural complications may include risk of bleeding and complications related to anesthesia. Monitor patients for procedural complications with AVANCE implantation and manage accordingly.

5.2 Transmission of Infectious Diseases Transmission of infectious diseases or agents may occur with AVANCE administration, as it is manufactured using tissues from human cadaveric donors. Donors are screened and tested for Human Immune-deficiency Virus 1 (HIV-1); Human Immune-deficiency Virus 2 (HIV-2); Hepatitis B Virus (HBV); Hepatitis C Virus (HCV); and Syphilis (Treponema pallidum). Additional testing for Human T-cell Leukemia-lymphoma Virus 1 (HTLV-1) and Human T-cell Leukemia-lymphoma Virus 2 (HTLV-2) may be performed as required by local regulatory authorities in US states. Only screening was performed for Creutzfeldt-Jakob disease (CJD). These measures do not eliminate the risk of transmitting these or other infectious diseases or agents. All infections thought to be transmitted by AVANCE should be reported to Axogen Corporation at 1‑888-296-4361.

The most common adverse reactions (incidence ≥2%) were procedural pain (4%) and hyperesthesia (3%). ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Customer Care at 1-888-296-4361 or customercare@axogeninc.com or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in one clinical trial cannot be directly compared to rates in other clinical trials and may not reflect the rates observed in practice. The safety database described in this section reflects exposure to AVANCE in the RECON Study. A total of 112 patients received AVANCE and 108 patients received NeuraGen ® (bovine nerve cuff) and were followed for a duration of 12 months. [see Clinical Studies ( 14 )] . A serious adverse reaction occurred in 1 patient, which was wound dehiscence. Table 2 lists the most common adverse reactions that occurred in ≥ 2% of patients in the RECON Study. Table 2. Adverse Reactions occurring in > 2% of Patients in the RECON Study Adverse Reactions AVANCE n = 112 n (%) Bovine Nerve Cuff n = 108 n (%) Implant site hyperesthesia 3 (3) 5 (5) Procedural pain 4 (4) 0 Other clinically significant adverse reactions that occurred in <2% of patients in AVANCE group include: implant site swelling (n=2), paraesthesia (n=2), hypertrophic scar (n=2), pyogenic granuloma (n=2), grade 3 neuroma (n=1), wound dehiscence (n=1), tendon adhesion (n=1), implant site nodule (n=1), osteomyelitis (n=1), and dermal cyst (n=1).

6.2 Postmarketing Experience Adverse Reactions from Observational Studies The safety of AVANCE was evaluated in an ongoing, multicenter, observational registry study in patients undergoing nerve repair. The registry assessed repairs using the Medical Research Council Classification (MRCC) across nerve types (sensory, motor, and mixed), gap lengths (5–210 mm), and body regions (upper extremity, head and neck, torso including breast, and lower extremity). Adverse reactions reported in the study include neuroma, seromas, implant site infection, tissue necrosis, nerve regeneration failure, hyperesthesia, hypoesthesia, AVANCE implantation error, and hematoma.

8.1 Pregnancy Risk Summary There are no data on the use of AVANCE in pregnant women. No animal reproductive and developmental toxicity studies have been conducted with AVANCE to assess whether it can cause harm to the mother or fetus when administered to a pregnant woman. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

8.2 Lactation Risk Summary There is no data on the effect of AVANCE on human milk, the effect on the breastfed infant, or the effect on milk production.

8.4 Pediatric Use The safety and effectiveness of AVANCE have been established in pediatric patients aged one month and older. The use of AVANCE in pediatric patients for the treatment of nerve discontinuity was supported by extrapolation of adult data from the RECON Study. [see Clinical Studies ( 14 )].

8.5 Geriatric Use There were 8 patients (4%) who were 65 years of age and older in the RECON Study. Clinical studies of AVANCE did not include sufficient numbers of patients aged 65 years and older to determine whether they respond differently from younger subjects.

Risk Summary There are no data on the use of AVANCE in pregnant women. No animal reproductive and developmental toxicity studies have been conducted with AVANCE to assess whether it can cause harm to the mother or fetus when administered to a pregnant woman. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

The safety and effectiveness of AVANCE have been established in pediatric patients aged one month and older. The use of AVANCE in pediatric patients for the treatment of nerve discontinuity was supported by extrapolation of adult data from the RECON Study. [see Clinical Studies ( 14 )].

There were 8 patients (4%) who were 65 years of age and older in the RECON Study. Clinical studies of AVANCE did not include sufficient numbers of patients aged 65 years and older to determine whether they respond differently from younger subjects.

AVANCE (acellular nerve allograft-arwx) is a sterile, acellular nerve scaffold derived from human cadaveric peripheral nerve tissue for surgical implantation. The processing method maintains the three-dimensional scaffold of the native peripheral nerve, including the endoneurial tubes, perineurium, epineurium, and microvasculature of the extracellular matrix (ECM). The processing removes cellular and noncellular components, including cells, fat, blood, axonal debris, and glycosaminoglycans. AVANCE is saturated in Lactated Ringer’s Solution prior to packaging and storage.

12.1 Mechanism of Action AVANCE is an acellular nerve scaffold intended to restore nerve function in the distal tissue. AVANCE provides structural and biochemical cues for axonal regeneration. The structural cue is provided by the intact endoneurial tubes. The biochemical cue is provided by the basement membrane proteins of the endoneurial tubes. The basement membrane of the endoneurial tubes includes many proteins, such as collagen, laminin, fibronectin, and proteoglycans. The laminin lining the endoneurial tubes of AVANCE has been shown in in vitro assays and animal studies to be bioactive by supporting Schwann cell migration, axon growth cone interactions, and neurite extension. Without the specific bioactive laminin composition, the neuroregenerative capacity is hindered. However, the exact mechanism of action is unknown.

12.2 Pharmacodynamics The pharmacodynamic effects of AVANCE are not known.

12.3 Pharmacokinetics The pharmacokinetic effects of AVANCE are not known.

AVANCE is an acellular nerve scaffold intended to restore nerve function in the distal tissue. AVANCE provides structural and biochemical cues for axonal regeneration. The structural cue is provided by the intact endoneurial tubes. The biochemical cue is provided by the basement membrane proteins of the endoneurial tubes. The basement membrane of the endoneurial tubes includes many proteins, such as collagen, laminin, fibronectin, and proteoglycans. The laminin lining the endoneurial tubes of AVANCE has been shown in in vitro assays and animal studies to be bioactive by supporting Schwann cell migration, axon growth cone interactions, and neurite extension. Without the specific bioactive laminin composition, the neuroregenerative capacity is hindered. However, the exact mechanism of action is unknown.

The pharmacodynamic effects of AVANCE are not known.

The pharmacokinetic effects of AVANCE are not known.

, Mutagenesis, Impairment of Fertility Conventional carcinogenicity and reproductive and developmental toxicity studies have not been conducted. Results from an in vitro bacterial reverse mutation assay demonstrated that AVANCE extracts are non-mutagenic.

17 PATIENT COUNSELING INFORMATION Discuss the following with the patient and/or caregivers.

• Procedural Complications Inform patients that procedure-related complications such as infection, pain, swelling, bleeding, scarring, neuroma formation, or delayed wound healing may occur after nerve repair surgery using AVANCE. Advise that careful postoperative monitoring is important. [see Warnings and Precautions ( 5.1 ) and Adverse Reactions ( 6 )].
• Transmission of Infectious Diseases Inform patients that AVANCE is made from cadaveric human tissue and, despite donor screening and validated processing steps, the risk of transmitting infectious diseases cannot be completely eliminated. [see Warnings and Precautions ( 5.2 )] .
• Advise the patient to closely follow the physician-prescribed rehabilitation program.

• Ensure the shipping container was received by the date indicated on the shipping container label and that sufficient dry ice is present within the shipping container. The amount of dry ice present within the shipping container can be assessed by the overall shipping container weight. The overall shipping container weight should be at least 12.0 lbs. for the 48-hour shipping container, 15.0 lbs. for the 72-hour shipping container, and 21.0 lbs. for the 120-hour shipping container.
• Store AVANCE at ≤-40°C (≤-40°F) and keep frozen until use.
• Do not use AVANCE if any component of the immediate container closure system or commercial carton has been compromised.
• Thaw AVANCE to room temperature without heating using room temperature sterile normal saline or Lactated Ringer’s Solution (LRS). Do not implant a partially or fully frozen product. Once thawed, it should not be placed back into the freezer. Thawed AVANCE must be implanted or discarded within 12 hours.
• Do not use if the lot number on the outer foil-poly pouch does not match the lot number on the outer carton.
• Any expired or thawed AVANCE that is not used in a surgical procedure should be destroyed in accordance with local, state, and federal or country regulations for disposal of human tissue. Contact Axogen Customer Care at 888-296-4361 for any issues with the condition of the packaging or graft, or for further instructions.