GLASSIA: Package Insert and Label Information

GLASSIA- .alpha.1-proteinase inhibitor human injection, solution
Baxalta US Inc.

1 INDICATIONS AND USAGE

GLASSIA, is an Alpha1 -Proteinase Inhibitor (Human), indicated for chronic augmentation and maintenance therapy in individuals with clinically evident emphysema due to severe hereditary deficiency of Alpha1 -PI, also known as alpha1 -antitrypsin (AAT) deficiency. GLASSIA increases antigenic and functional (anti-neutrophil elastase capacity, ANEC) serum levels and antigenic lung epithelial lining fluid levels of Alpha1 -PI.

Limitations of Use:

  • The effect of augmentation therapy with GLASSIA or any Alpha1 -PI product on pulmonary exacerbations and on the progression of emphysema in Alpha1 -PI deficiency has not been conclusively demonstrated in randomized, controlled clinical trials.
  • Clinical data demonstrating the long-term effects of chronic augmentation and maintenance therapy of individuals with GLASSIA are not available.
  • GLASSIA is not indicated as therapy for lung disease in patients in whom severe Alpha1 -PI deficiency has not been established.

2 DOSAGE AND ADMINISTRATION

For intravenous use only.

2.1 Dosage

  • Administer 60 mg/kg body weight of GLASSIA once weekly by intravenous infusion.
  • Dose ranging studies using efficacy endpoints have not been performed.
  • The carton and label on each vial of GLASSIA show the actual amount of functionally active Alpha1 -PI in milligrams.

2.2 Preparation

  1. Use aseptic technique.
  2. Allow the product to reach room temperature prior to infusing and administer within three hours of entering the vials.
  3. Inspect the vial of GLASSIA. The solution should be clear and colorless to yellow-green and may contain a few protein particles. Discard if the product is cloudy.
  4. The product is suitable for infusion directly from the vial or pooled into a sterile container for intravenous infusion.
  5. Use a vented spike (not supplied) to withdraw the solution from the vial.
  6. Then use a needle (not supplied) to transfer the solution into the intravenous infusion container.
  7. If using multiple vials to achieve the desired dose, pool GLASSIA into the infusion container by repeating Steps 5 and 6 with a new vented spike and transfer needle for each vial.

2.3 Administration

For intravenous infusion only.

GLASSIA should be administered by a healthcare professional or self-administered by the patient/caregiver after appropriate training. For self-administration, provide the patient/caregiver with detailed instructions and adequate training for infusion in the home or other appropriate setting [see Patient Counseling Information (17)].

  1. Use aseptic technique.
  2. Inspect parenteral products visually for particulate matter and discoloration prior to administration whenever solution and container permit.
  3. Administer GLASSIA alone. Do not mix with other agents or diluting solutions.
  4. When infusing directly from the vials, use a vented spike (not supplied). If the contents of vials have been pooled to a sterile intravenous container, use an appropriate intravenous administration set.
  5. Always use a 5 micron in-line filter (minimum filter diameter of 32 mm to ensure optimal performance, not supplied) during infusion.
  6. Administer GLASSIA within three hours of entering the vials to avoid the potential ill effect of any inadvertent microbial contamination.
  7. Administer GLASSIA at room temperature through an appropriate intravenous administration set at a rate not to exceed 0.2 mL/kg body weight per minute, and as determined by the response and comfort of the patient. The recommended dosage of 60 mg/kg at a rate of 0.2 mL/kg/min will take approximately 15 minutes to infuse.
  8. Monitor the infusion rate closely during administration and observe the patient for signs of infusion related reactions. If infusion related adverse reactions occur, reduce the rate or interrupt the infusion as appropriate until the symptoms subside. Resume the infusion at a rate tolerated by the patient, except in the case of severe reaction [see Warnings and Precautions (5.1)].
  9. Following administration, discard all open vials, unused solution and administration equipment.

3 DOSAGE FORMS AND STRENGTHS

GLASSIA is available as a single-dose vial containing approximately 1 gram of functional Alpha1 -PI in 50 mL of ready to use solution.

4 CONTRAINDICATIONS

GLASSIA is contraindicated in:

  • immunoglobulin A (IgA) deficient patients with antibodies against IgA.
  • individuals with a history of anaphylaxis or other severe systemic reaction to Alpha1 -PI products.

5 WARNINGS AND PRECAUTIONS

5.1 Hypersensitivity Reactions

GLASSIA may contain trace amounts of IgA. Patients with known antibodies to IgA, which can be present in patients with selective or severe IgA deficiency, have a greater risk of developing severe hypersensitivity and anaphylactic reactions. Monitor vital signs continuously and observe the patient carefully throughout the infusion. Discontinue the infusion if hypersensitivity symptoms occur and administer appropriate emergency treatment. Have epinephrine and/or other appropriate supportive therapy available for the treatment of any acute anaphylactic or anaphylactoid reaction.

5.2 Transmissible Infectious Agents

Because this product is made from human plasma, it may carry a risk of transmitting infectious agents, such as viruses, the variant Creutzfeldt-Jakob disease (vCJD) and theoretically, the Creutzfeldt-Jakob disease (CJD) agent. This also applies to unknown or emerging viruses and other pathogens. The risk of transmitting an infectious agent has been minimized by screening plasma donors for prior exposure to certain viruses, by testing for the presence of certain current virus infections and by inactivating and removing certain viruses during the manufacturing process. Despite these measures, such products may still potentially transmit human pathogenic agents.

All infections thought by a physician possibly to have been transmitted by this product should be reported by the physician or other healthcare provider to Takeda Pharmaceuticals U.S.A. at 1-877-TAKEDA-7 (1-877-825-3327) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

No seroconversions for hepatitis B or C (HBV or HCV) or human immunodeficiency virus (HIV) or any other known infectious agent were reported with the use of GLASSIA during the clinical trials.

6 ADVERSE REACTIONS

The serious adverse reaction observed during clinical trials with GLASSIA was exacerbation of chronic obstructive pulmonary disease (COPD).

The most common adverse reactions (>0.5% of infusions) in clinical trials were headache and upper respiratory infection.

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

The safety profile of GLASSIA was evaluated in a randomized, double-blind, active-control trial and an open-label, non-parallel, dose-escalation trial, in 65 subjects with pre-augmentation therapy serum Alpha1 -PI levels less than 11 microM. In the randomized, double-blind, active-control trial, 50 subjects received weekly infusions of GLASSIA or the comparator Alpha1 -PI product, Prolastin, at a dosage of 60 mg/kg for a total of 12 doses after which all subjects remaining in the trial were treated for another 12 weeks with GLASSIA only. Overall, 17 subjects received 12 doses and 32 subjects received 22 — 24 doses of GLASSIA during the trial. (One subject randomized to the comparator Alpha1 -PI product did not receive any treatment with GLASSIA during the last 12 weeks of the trial.). In the open label, non-parallel, dose-escalation trial, 18 subjects received a single infusion of GLASSIA at dosages of 30, 60 or 120 mg/kg. The population treated in the two trials was 40-74 years old, 54% male, 100% Caucasian.

Tables 1 and 2 compare the adverse reactions reported during the initial 12 weeks (double-blind portion) of the randomized, active comparator trial in all subjects treated with GLASSIA with reactions in the concurrent Prolastin control group. Table 3 compares the frequency of adverse reactions as a percentage of all infusions for GLASSIA and Prolastin-treated subjects over the entire trial period.

Table 1: Number of Subjects/Infusions/Adverse Reactions * Occurring during the First 12 Weeks of Treatment
*
An adverse reaction is any adverse event which met any of the following criteria: (a) an adverse event that began within 72 hours following the end of product infusion, or (b) an adverse event considered by either the investigator or sponsor to be at least possibly related to product administration, or (c) an adverse event for which causality assessment was missing or indeterminate.
GLASSIA Prolastin
No. of subjects treated 33 17
No. of infusions 393 190
No. of subjects with serious adverse reactions (%)* 1 (3%) 1 (6%)
No. of subjects experiencing an adverse reaction * (%) 22 (67%) 15 (88%)
No. of adverse reactions * 47 39
Table 2: Adverse Reactions * Occurring in > 5% of Subjects during the First 12 Weeks of Treatment
GLASSIA
No. of subjects: 33
Prolastin
No. of subjects: 17
Adverse Event (AE) No. of subjects with adverse reactions *(AR)
(percentage of all subjects)
No. of subjects with adverse reactions *(AR)
(percentage of all subjects)
*
An adverse reaction is any adverse event which met any of the following criteria: (a) an adverse event that began within 72 hours following the end of product infusion, or (b) an adverse event considered by either the investigator or sponsor to be at least possibly related to product administration, or (c) an adverse event for which causality assessment was missing or indeterminate.
Cough 3 (9%) 4 (24%)
Upper respiratory tract infection 3 (9%) 0 (0%)
Headache 3 (9%) 3 (18%)
Sinusitis 2 (6%) 1 (6%)
Chest discomfort 2 (6%) 0 (0%)
Dizziness 2 (6%) 0 (0%)
Hepatic enzyme increased 2 (6%) 0 (0%)
Table 3: Adverse Reactions * Frequency as a % of all Infusions (> 0.5%)
GLASSIA
No. of infusions: 960
Prolastin
No. of infusions: 190
Adverse Event (AE) No. of adverse reactions * (AR)
(percentage of all infusions)
No. of adverse reactions * (AR)
(percentage of all infusions)
*
An adverse reaction is any adverse event which met any of the following criteria: (a) an adverse event that began within 72 hours following the end of product infusion, or (b) an adverse event considered by either the investigator or sponsor to be at least possibly related to product administration, or (c) an adverse event for which causality assessment was missing or indeterminate.
Throughout entire 24-week double-blind plus open-label trial period
Throughout initial 12-week double-blind period
Upper respiratory tract infection 8 (0.8%) 0 (0.0%)
Headache 6 (0.6%) 3 (1.6%)

Chronic Obstructive Pulmonary Disease (COPD) Exacerbations

During the 12-week double blind portion of the randomized, active comparator trial, 4 subjects (12%) had a total of 7 exacerbations of chronic obstructive pulmonary disease (COPD) during GLASSIA treatment and 5 subjects (29%) had a total of 6 exacerbations of COPD during Prolastin treatment. Seventeen additional exacerbations in 14 subjects (28%) occurred during the 12-week open-label treatment period with GLASSIA. The overall rate of pulmonary exacerbations during treatment with either product was 1.3 exacerbations per subject per year. Testing for viral markers for HBV, HCV, HIV-1 and HIV-2 showed no seroconversions during either trial.

Immunogenicity

As with all therapeutic proteins, there is a potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to GLASSIA with the incidence of antibodies to other products may be misleading.

In the double blind, randomized, active comparator trial of GLASSIA, low level anti-GLASSIA antibodies were detected in one subject at one time point (Week 12) and returned to negative at the end of the study (Week 24) despite continuous exposure to GLASSIA. No immune system adverse reactions were reported.

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