A Study of Administration of Peginterferon Alfa-2a [Pegasys] by Autoinjector Versus Pre-filled Syringe in Patients With Chronic Hepatitis C

Study Overview
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Brief Summary
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This randomized, cross-over, open label study will compare the tolerability and handling of application of peginterferon alfa-2a [Pegasys] by autoinjector versus pre-filled syringe in patients with chronic hepatitis C, either on treatment with peginterferon alfa-2a for at least 12 weeks or treatment-naïve for peginterferon alfa-2a. Patients will be randomized to self-injection of 180mcg peginterferon alfa-2a once a week using either an autoinjector or a prefilled syringe for 3 weeks, then switch to use the other method of injection for another 3 weeks. Anticipated time on study treatment is 6 weeks. Target sample size is <100 patients.

Official Title
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Tolerability and User Handling Study of an Autoinjector to Administer 180 µg/0.5 mL Peginterferon Alfa-2a (Pegasys, PEG-IFN)

Conditions
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Hepatitis C, Chronic

Intervention / Treatment
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* Device: Autoinjector
* Device: Pre-filled syringe


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patients, >/=18 years of age chronic hepatitis C on treatment with peginterferon alfa-2a for >/= 12 weeks at baseline, or treatment-naïve for peginterferon alfa-2a Exclusion Criteria: history or evidence of decompensated liver disease autoimmune hepatitis hypersensitivity to peginterferon alfa-2a or any of its components concomitant treatment that requires administration by self-injection, or prior use of an autoinjector

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Peginterferon via auto-injector device. All participants will receive Peginterferon in a cross-over design. | Device: Autoinjector<br>* Participants received Peginterferon alfa-2a 180 microgram subcutaneously once a week by autoinjector for 3 weeks.<br>|
| Active Comparator: 2<br>Peginterferon via pre-filled syringe. All participants will receive Peginterferon in a cross-over design. | Device: Pre-filled syringe<br>* Participants received Peginterferon alfa-2a 180 microgram subcutaneously once a week by pre-filled syringe for 3 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility of Peginterferon Alfa-2a Administration by Autoinjector | The feasibility of PEG-INF administration by AI was assessed by Injection Method Observational Survey questions, based on following pre-defined questions using a Yes or No response: 1) Did the participant exhibit any nervousness prior to the injection? 2) Did the participant exhibit any difficulty initiating the injection? 3) Did the participant appear confident performing the injection? 4) Did the participant follow the instructions for performing the injection without the need for additional instructions or guidance? 5) Did the participant experience any technical problems with the device or syringe during the injection? 6) Did the participant withdraw the device/syringe before the injection was complete? 7) Did the participant exhibit any visible pain or physical discomfort? 8) Did the participant appear to be satisfied using the device or syringe? 9) Did the participant exhibit any frustration using the syringe or device? | Week 1, Day 1 (Baseline), Week 2 (Day 8 ± 2 days), Week 3 (Day 15 ± 2 days), Week 4 (Day 22 ± 2 days), Week 5 (Day 29 ± 2 days), Week 6 (Day 36 ± 2 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Marked Laboratory Abnormalities in Hemoglobin, Albumin and Total Protein | A marked abnormality was defined as a test result which was outside of the marked abnormality range, and which represented a clinically relevant change from baseline of at least the designated amount. The marked reference range for hemoglobin was 110-200 (gram per liter [g/L]), albumin was 30.0-n.d g/L, and total protein was 55-87 g/L. The clinical relevant change (decrease/ increase) for hemoglobin was (15%, 15%), albumin was (20%, n.d) and total protein was (20%, 20%) respectively. | Week 1, Day 1 (Baseline), Week 4 (Day 22 ± 2 days), and Week 6 (Day 36 ± 2 days) | 
| Number of Participants With Marked Laboratory Abnormalities in Hematocrit | A marked abnormality was defined as a test result which was outside of the marked abnormality range, and which represented a clinically relevant change from baseline of at least the designated amount. The marked reference range for hematocrit was 0.31-0.56 fraction. The clinical relevant change (decrease/ increase) for hematocrit was (15%, 15%). | Week 1, Day 1 (Baseline), Week 4 (Day 22 ± 2 days), and Week 6 (Day 36 ± 2 days) | 
| Number of Participants With Marked Laboratory Abnormalities in Platelet, White Blood Cell (WBC), Basophil, Eosinophil, Lymphocyte, Monocyte and Neutrophil | A marked abnormality was defined as a test result which was outside of the marked abnormality range, and which represented a clinically relevant change from baseline of at least the designated amount. The marked reference range for Platelets was 100-550 (10*9/L), for WBC was 3.0-18.0 (10*9/L), for Basophils was 0.00-0.40 (10*9/L), for Eosinophil was 0.00-0.90 (10*9/L), for Lymphocytes was 0.70-7.60 (10*9/L), Monocyte was 0.00-1.70 (10*9/L), and Neutrophil 1.50-9.25 (10*9/L). The clinical relevant change (decrease/increase) for platelet was (30%, 50%), WBC was (30%, 30%), Basophil was (n.d, 100%), Eosinophil was (n.d, 100%), Lymphocyte was (30%, 30%), Monocyte was (n.d, 100%) and Neutrophil was (20%, 20%) respectively. | Week 1, Day 1 (Baseline), Week 4 (Day 22 ± 2 days), and Week 6 (Day 36 ± 2 days) | 
| Number of Participants With Marked Laboratory Abnormalities in Right Blood Cell (RBC) | A marked abnormality was defined as a test result which was outside of the marked abnormality range, and which represented a clinically relevant change from baseline of at least the designated amount. The marked reference range for RBC was 3.80-6.10 (10*12/L). The clinical relevant change (decrease/ increase) for RBC was (15%, 15%). | Week 1, Day 1 (Baseline), Week 4 (Day 22 ± 2 days), and Week 6 (Day 36 ± 2 days) | 
| Number of Participants With Marked Laboratory Abnormalities in Prothrombin Time (PT) International Normalized Ratio (INR) | A marked abnormality was defined as a test result which was outside of the marked abnormality range, and which represented a clinically relevant change from baseline of at least the designated amount. The marked reference range for PT-INR was n.d.-2.00. The clinical relevant change (decrease/ increase) for PT-INR was (n.d, 30%). | Week 1, Day 1 (Baseline), Week 4 (Day 22 ± 2 days), and Week 6 (Day 36 ± 2 days) | 
| Number of Participants With Marked Laboratory Abnormalities in Serum Glutamic Oxaloacetic Transaminase (SGOT), Serum Glutamic-Pyruvic Transaminase (SGPT), and Alkaline Phosphatase | A marked abnormality was defined as a test result which was outside of the marked abnormality range, and which represented a clinically relevant change from baseline of at least the designated amount. The marked reference range for SGOT was 0-80 (Units Per Litre [U/L]), SGPT was 0-110 U/L, and alkaline phosphatase was 0-220 U/L. The clinical relevant change (decrease/ increase) for SGOT was (n.d, 50%), SGPT was (n.d, 50%), and ALP was (n.d, 50%) respectively. | Week 1, Day 1 (Baseline), Week 4 (Day 22 ± 2 days), and Week 6 (Day 36 ± 2 days) | 
| Number of Participants With Marked Laboratory Abnormalities in Blood Urea Nitrogen (BUN), Chloride, Potassium, Sodium, Calcium, Glucose | A marked abnormality was defined as a test result which was outside of the marked abnormality range, and which represented a clinically relevant change from baseline of at least the designated amount. The marked reference range for BUN was 0.0-14.3 (millimoles per Liter [mmol/L]), Chloride was 95-115 (mmol/L), Potassium was 2.9-5.8 (mmol/L), Sodium was 130-150 (mmol/L), Calcium was 2.00-2.90 (mmol/L), and Glucose was 2.80-11.10 (mmol/L). The clinical relevant change (decrease/ increase) for BUN was (n.d, 50%), Chloride was (7%, 7%), Potassium was (20%, 20%), Sodium was (7%, 7%), Calcium was (10%, 10%), and Glucose was (75%, 75%) respectively. | Week 1, Day 1 (Baseline), Week 4 (Day 22 ± 2 days), and Week 6 (Day 36 ± 2 days) | 
| Number of Participants With Marked Laboratory Abnormalities in Creatinine | A marked abnormality was defined as a test result which was outside of the marked abnormality range, and which represented a clinically relevant change from baseline of at least the designated amount. The marked reference range for Creatinine was 0- 154 (micromoles/liter [umol/L]). The clinical relevant change (decrease/ increase) for Creatinine was (n.d, 50%). | Week 1, Day 1 (Baseline), Week 4 (Day 22 ± 2 days), and Week 6 (Day 36 ± 2 days) | 
| Number of Participants With Abnormalities in Pulse Rate, Temperature, and Blood Pressure | The pulse rate, temperature and blood pressure was assessed during a physical examination. Pulse rate was assessed in beats per minute (bpm), temperature was assessed in degree Celsius (°С), and blood pressure was assessed in millimeters of mercury (mmHg). Vital signs were taken while the participant was supine. | Week 1, Day 1 (Baseline), Week 2 (Day 8 ± 2 days), Week 3 (Day 15 ± 2 days), Week 4 (Day 22 ± 2 days), Week 5 (Day 29 ± 2 days), Week 6 (Day 36 ± 2 days) | 
| Number of Participants With Abnormalities in Electrocardiograms | A 12-lead ECG was recorded after the participant had been in a semi-supine position for at least 10 minutes. Any clinically significant abnormalities noted on an ECG after the first dose of study drug were captured as AEs | Week 1, Day 1 (Baseline), Week 4 (Day 22 ± 2 days), and Week 6 (Day 36 ± 2 days) | 
| Number of Participants With Adverse Events (AE) | An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. | Upto Day 36 |