Multiple Sclerosis
Conditions
Brief summary
The primary objective of the study was to evaluate the safe and effective use of the single-use autoinjector for the intramuscular (IM) delivery of liquid Avonex® (interferon beta-1a) in participants with multiple sclerosis (MS).
Detailed description
The Main Study was a 4-week treatment period which consisted of 1 Avonex manual injection using a prefilled syringe, followed by 3 Avonex injections using the single-use autoinjector. The Extension Study was designed to provide continuation of treatment with the Avonex single-use autoinjector to eligible participants who completed the Main Study for up to an additional 12 weeks, and to obtain additional safety and preference data for the Avonex single-use autoinjector. Participants were enrolled under the initial study protocol (Initial Subject Subset); the study was subsequently suspended. Changes were made to the protocol (including modifications to the autoinjector needle), and additional participants were enrolled (Main Subject Subset).
Interventions
DEVICEsingle-use autoinjector with a prefilled liquid Avonex syringe
DEVICEAvonex prefilled syringe via manual IM injection
Sponsors
Biogen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (PHI) in accordance with national and local subject privacy regulations. 2. Must be 18 to 65 years old, inclusive, at the time of informed consent. 3. Must currently be self-administering Avonex Prefilled Syringes to treat MS and must have been self-administering Avonex Prefilled Syringes for the 12 weeks prior to the Screening Visit. 4. In the investigator's opinion, subjects must be willing and able to self-administer all injections required by the protocol. 5. Must speak English. 6. All male subjects and female subjects of child-bearing potential must practice effective contraception during the study.
Exclusion criteria
1. History of seizure disorder or unexplained blackouts OR history of a seizure within 3 months prior to the Screening Visit. 2. History of suicidal ideation within 3 months prior to Day 1 or an episode of severe depression within 3 months prior to Day 1. Severe depression is defined as any episode of depression that requires hospitalization, or the initiation of antidepressant therapy, or an increase in the dose of an existing regimen of antidepressant therapy. NOTE: Subjects receiving ongoing antidepressant therapy are not excluded from the study unless the dose has been increased within the 3 months prior to the Screening Visit. 3. Clinically significant local infection (for example cellulitis, abscess) or systemic infection (pneumonia, septicemia), at the discretion of the Investigator. 4. Known history of Human Immunodeficiency Virus (HIV). 5. Known history of, or positive test result for hepatitis C virus (test for hepatitis C virus antibody \[HCV Ab\]) or Hepatitis B virus (test for Hepatitis B Surface Antigen \[HBsAg\] and/or Hepatitis B Core Antibody \[HBcAb\]).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants in the Main Subset With Overall Success Using the Avonex Single-Use Autoinjector | Day 22 | A trainer/observer documented the participant's ability to self-inject with the Avonex single-use autoinjector and completed an observation form. Overall success in using the device for each participant was defined as no failures occurring in any step (ie, device set-up, self-administration of injection, and capping/disposal of the device) during the participant's use of the single-use Avonex autoinjector. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With No Erythema, Induration, or Tenderness, and Normal Temperature at the Injection Site After Injection With the Avonex Single-use Autoinjector | Day 1, Day 8 through 22 (highest severity reported between Days 8 and 22) | The clinician/investigator evaluated the injection site for erythema, induration, and tenderness as none, mild, moderate, or severe after the use of the Avonex single-use autoinjector. Temperature at the injection site was evaluated as normal, warm, or hot. Those participants having no erythema, induration, or tenderness, and normal temperature at the injection site after injection are presented. |
| Mean Score for Ease of Use Grading Scale | Day 1, Day 8, Day 15, Day 22 | Participants scored the ease of use of the Avonex manual injector (Day 1) and single-use autoinjector (Days 8, 15, 22) using a scale that ranged from 0 (extremely difficult) to 10 (extremely easy). |
| Percentage of Participants Who Rated the Avonex Single-use Autoinjector Printed and DVD Training Materials as Very Effective | Day 8, Day 15, Day 22 | Participants evaluated how effective the printed and DVD instructions were in educating how to use the Avonex single-use autoinjector. Participants could choose one of the following descriptive answers: not effective at all, somewhat ineffective, neutral, somewhat effective, or very effective. |
| Number of Participants in the Initial Subset Who Were Satisfied With the Avonex Single-Use Autoinjector | Day 23 | Number of participants in the Initial Subset who answered yes to the question Were you satisfied with this single-use injector? on the Subject Satisfaction Questionnaire. |
| Percentage of Participants Who Indicated No Difficulty With the Injection Procedure of the Manual Injection or the Avonex Single-use Autoinjector | Day 1, Day 8, Day 15, Day 22 | Participants assessed whether they had experienced any difficulty with the procedure in preparing, injecting, removing, and disposing process after each injection with the Avonex single-use autoinjector by answering yes or no to the following question: Did you have any difficulty with your injection? The percentage of participants answering no to this question for both the manual injection on Day 1 and the autoinjector on Days 8. 15 and 22 are presented. |
| Percentage of Participants Who Indicated a Preference for the Avonex Single-use Autoinjector Over the Manual Avonex Prefilled Syringe | Day 23 | Participants were asked whether they preferred using the Avonex single-use autoinjector over the manual Avonex prefilled syringe. Preference was defined as participants answering yes to the following question: Do you prefer this single-use autoinjector over the manual injection? |
| Mean Pain Score After Injection | Day 1, Day 8, Day 15, Day 22 | Participants scored their pain level after the use of the manual prefilled syringe on Day 1 and the Avonex single-use autoinjector on Days 8, 15, and 22 on a scale ranging from 0 (no pain) to 10 (extremely painful). |
| Mean Score for Initial Subset on Autoinjector Instructions Grading Scale | Day 8 | Participants in the Initial Subset were asked to answer the question How satisfied are you with the presentation of the autoinjector instructions? on a rating scale of 0 (extremely dissatisfied) to 10 (extremely satisfied). |
Countries
United States
Participant flow
Recruitment details
Recruitment occurred in the following stages: Main Study (Initial Subset and Main Subset enrolled), and Extension Study. Initial subset participants were withdrawn when the study was suspended. After a protocol amendment, the Main Subset participants were enrolled. Only those in the Main Subset had the option to participate in the Extension Study.
Participants by arm
| Arm | Count |
|---|---|
| Avonex Single-Use Autoinjector: Main Subset Participants received open label weekly treatment with Avonex 30 mcg intramuscular (IM) injections, provided in Avonex prefilled syringes.
In the Main Study, injection #1: administration of Avonex prefilled syringe via manual IM injection on Day 1. Injections #2, #3, and #4: administration of Avonex prefilled syringe using the single-use autoinjector on Days 8, 15, and 22, respectively. In the Extension Study, participants were to continue treatment with the Avonex single-use autoinjector for up to an additional 12 weeks.
Main Subset participants were enrolled after study suspension and could enroll in the Extension Study. | 74 |
| Avonex Single-Use Autoinjector: Initial Subset Participants received open label weekly treatment with Avonex 30 mcg intramuscular (IM) injections, provided in Avonex prefilled syringes.
In the Main Study, injection #1: administration of Avonex prefilled syringe via manual IM injection on Day 1. Injections #2, #3, and #4: administration of Avonex prefilled syringe using the single-use autoinjector on Days 8, 15, and 22, respectively. In the Extension Study, participants were to continue treatment with the Avonex single-use autoinjector for up to an additional 12 weeks.
Initial Subset participants were enrolled in the Main Study prior to study suspension and could not enroll in the Extension Study. | 21 |
| Total | 95 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Extension Study | Lost to Follow-up | 0 | 1 |
| Extension Study | Physician Decision | 0 | 2 |
| Main Study: After Study Restart | Adverse Event | 0 | 2 |
| Main Study: After Study Restart | Noncompliance | 0 | 1 |
| Main Study: Prior to Study Suspension | Adverse Event | 1 | 0 |
| Main Study: Prior to Study Suspension | Study Suspension | 11 | 0 |
| Main Study: Prior to Study Suspension | Subject Was Withdrawn | 2 | 0 |
Baseline characteristics
| Characteristic | Avonex Single-Use Autoinjector: Main Subset | Avonex Single-Use Autoinjector: Initial Subset | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 0 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 72 Participants | 21 Participants | 93 Participants |
| Sex: Female, Male Female | 64 Participants | 18 Participants | 82 Participants |
| Sex: Female, Male Male | 10 Participants | 3 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 33 / 72 | 7 / 19 |
| serious Total, serious adverse events | 0 / 72 | 0 / 19 |
Outcome results
Primary
Percentage of Participants in the Main Subset With Overall Success Using the Avonex Single-Use Autoinjector
A trainer/observer documented the participant's ability to self-inject with the Avonex single-use autoinjector and completed an observation form. Overall success in using the device for each participant was defined as no failures occurring in any step (ie, device set-up, self-administration of injection, and capping/disposal of the device) during the participant's use of the single-use Avonex autoinjector.
Time frame: Day 22
Population: Participants in the Main Subset who received an injection of Avonex prefilled syringe as a manual IM injection, at least 1 injection of Avonex prefilled syringe using the autoinjector, and had a completed Observation Form were included in the analysis. Missing data were not imputed. All analyses are based on observed data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Avonex Single-Use Autoinjector: Main Subset | Percentage of Participants in the Main Subset With Overall Success Using the Avonex Single-Use Autoinjector | 89 percentage of participants |
Other Pre-specified
Mean Pain Score After Injection
Participants scored their pain level after the use of the manual prefilled syringe on Day 1 and the Avonex single-use autoinjector on Days 8, 15, and 22 on a scale ranging from 0 (no pain) to 10 (extremely painful).
Time frame: Day 1, Day 8, Day 15, Day 22
Population: Participants in the Main and Initial Subsets who received at least 1 dose of Avonex injection using the Avonex single-use autoinjector. Missing data were not imputed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Avonex Single-Use Autoinjector: Main Subset | Mean Pain Score After Injection | Day 1 (Manual Injection) n=72, 19 | 1.7 scores on a scale | Standard Deviation 1.76 |
| Avonex Single-Use Autoinjector: Main Subset | Mean Pain Score After Injection | Day 8 (Autoinjector) n= 72, 18 | 1.0 scores on a scale | Standard Deviation 1.46 |
| Avonex Single-Use Autoinjector: Main Subset | Mean Pain Score After Injection | Day 15 (Autoinjector) n=71, 16 | 1.3 scores on a scale | Standard Deviation 1.64 |
| Avonex Single-Use Autoinjector: Main Subset | Mean Pain Score After Injection | Day 22 (Autoinjector) n=70, 7 | 0.7 scores on a scale | Standard Deviation 1.13 |
| Avonex Single-Use Autoinjector: Initial Subset | Mean Pain Score After Injection | Day 22 (Autoinjector) n=70, 7 | 2.4 scores on a scale | Standard Deviation 2.99 |
| Avonex Single-Use Autoinjector: Initial Subset | Mean Pain Score After Injection | Day 1 (Manual Injection) n=72, 19 | 2.5 scores on a scale | Standard Deviation 2.87 |
| Avonex Single-Use Autoinjector: Initial Subset | Mean Pain Score After Injection | Day 15 (Autoinjector) n=71, 16 | 2.1 scores on a scale | Standard Deviation 1.95 |
| Avonex Single-Use Autoinjector: Initial Subset | Mean Pain Score After Injection | Day 8 (Autoinjector) n= 72, 18 | 1.9 scores on a scale | Standard Deviation 2.19 |
Other Pre-specified
Mean Score for Ease of Use Grading Scale
Participants scored the ease of use of the Avonex manual injector (Day 1) and single-use autoinjector (Days 8, 15, 22) using a scale that ranged from 0 (extremely difficult) to 10 (extremely easy).
Time frame: Day 1, Day 8, Day 15, Day 22
Population: Participants who received at least one injection with the Avonex Single-use Autoinjector. Missing data were not imputed. n=number of participants who received an injection and had an assessment at the given timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Avonex Single-Use Autoinjector: Main Subset | Mean Score for Ease of Use Grading Scale | Day 1 (Manual Injection) n=72, 19 | 8.1 scores on a scale | Standard Deviation 2.64 |
| Avonex Single-Use Autoinjector: Main Subset | Mean Score for Ease of Use Grading Scale | Day 8 (Autoinjector) n= 72, 18 | 8.9 scores on a scale | Standard Deviation 1.96 |
| Avonex Single-Use Autoinjector: Main Subset | Mean Score for Ease of Use Grading Scale | Day 15 (Autoinjector) n=71, 16 | 8.7 scores on a scale | Standard Deviation 2.47 |
| Avonex Single-Use Autoinjector: Main Subset | Mean Score for Ease of Use Grading Scale | Day 22 (Autoinjector) n=70, 7 | 9.3 scores on a scale | Standard Deviation 1.87 |
| Avonex Single-Use Autoinjector: Initial Subset | Mean Score for Ease of Use Grading Scale | Day 22 (Autoinjector) n=70, 7 | 5.9 scores on a scale | Standard Deviation 3.13 |
| Avonex Single-Use Autoinjector: Initial Subset | Mean Score for Ease of Use Grading Scale | Day 1 (Manual Injection) n=72, 19 | 7.4 scores on a scale | Standard Deviation 2.41 |
| Avonex Single-Use Autoinjector: Initial Subset | Mean Score for Ease of Use Grading Scale | Day 15 (Autoinjector) n=71, 16 | 6.7 scores on a scale | Standard Deviation 3.07 |
| Avonex Single-Use Autoinjector: Initial Subset | Mean Score for Ease of Use Grading Scale | Day 8 (Autoinjector) n= 72, 18 | 6.8 scores on a scale | Standard Deviation 3.39 |
Other Pre-specified
Mean Score for Initial Subset on Autoinjector Instructions Grading Scale
Participants in the Initial Subset were asked to answer the question How satisfied are you with the presentation of the autoinjector instructions? on a rating scale of 0 (extremely dissatisfied) to 10 (extremely satisfied).
Time frame: Day 8
Population: Participants in the Initial Subset who received at least one injection with the Avonex single-use autoinjector and completed the grading scale.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Avonex Single-Use Autoinjector: Main Subset | Mean Score for Initial Subset on Autoinjector Instructions Grading Scale | 9.5 scores on a scale | Standard Deviation 0.71 |
Other Pre-specified
Number of Participants in the Initial Subset Who Were Satisfied With the Avonex Single-Use Autoinjector
Number of participants in the Initial Subset who answered yes to the question Were you satisfied with this single-use injector? on the Subject Satisfaction Questionnaire.
Time frame: Day 23
Population: Participants in the Initial Subset who received at least 1 injection with autoinjector who had a complete Subject Satisfaction Questionnaire.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Avonex Single-Use Autoinjector: Main Subset | Number of Participants in the Initial Subset Who Were Satisfied With the Avonex Single-Use Autoinjector | 14 participants |
Other Pre-specified
Percentage of Participants Who Indicated a Preference for the Avonex Single-use Autoinjector Over the Manual Avonex Prefilled Syringe
Participants were asked whether they preferred using the Avonex single-use autoinjector over the manual Avonex prefilled syringe. Preference was defined as participants answering yes to the following question: Do you prefer this single-use autoinjector over the manual injection?
Time frame: Day 23
Population: Participants who received at least 1 injection with autoinjector and had a complete questionnaire. Missing data were not imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Avonex Single-Use Autoinjector: Main Subset | Percentage of Participants Who Indicated a Preference for the Avonex Single-use Autoinjector Over the Manual Avonex Prefilled Syringe | 94 percentage of participants |
| Avonex Single-Use Autoinjector: Initial Subset | Percentage of Participants Who Indicated a Preference for the Avonex Single-use Autoinjector Over the Manual Avonex Prefilled Syringe | 53 percentage of participants |
Other Pre-specified
Percentage of Participants Who Indicated No Difficulty With the Injection Procedure of the Manual Injection or the Avonex Single-use Autoinjector
Participants assessed whether they had experienced any difficulty with the procedure in preparing, injecting, removing, and disposing process after each injection with the Avonex single-use autoinjector by answering yes or no to the following question: Did you have any difficulty with your injection? The percentage of participants answering no to this question for both the manual injection on Day 1 and the autoinjector on Days 8. 15 and 22 are presented.
Time frame: Day 1, Day 8, Day 15, Day 22
Population: Participants in the Main Subset who received at least one injection with the Avonex single-use autoinjector and submitted an assessment of injection procedure form. Missing data were not imputed. n=number of participants with assessment at the given timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Avonex Single-Use Autoinjector: Main Subset | Percentage of Participants Who Indicated No Difficulty With the Injection Procedure of the Manual Injection or the Avonex Single-use Autoinjector | Day 1 (Manual Injection); n=70 | 89 percentage of participants |
| Avonex Single-Use Autoinjector: Main Subset | Percentage of Participants Who Indicated No Difficulty With the Injection Procedure of the Manual Injection or the Avonex Single-use Autoinjector | Day 8 (Autoinjector); n=71 | 90 percentage of participants |
| Avonex Single-Use Autoinjector: Main Subset | Percentage of Participants Who Indicated No Difficulty With the Injection Procedure of the Manual Injection or the Avonex Single-use Autoinjector | Day 15 (Autoinjector); n=71 | 90 percentage of participants |
| Avonex Single-Use Autoinjector: Main Subset | Percentage of Participants Who Indicated No Difficulty With the Injection Procedure of the Manual Injection or the Avonex Single-use Autoinjector | Day 22 (Autoinjector); n=71 | 90 percentage of participants |
Other Pre-specified
Percentage of Participants Who Rated the Avonex Single-use Autoinjector Printed and DVD Training Materials as Very Effective
Participants evaluated how effective the printed and DVD instructions were in educating how to use the Avonex single-use autoinjector. Participants could choose one of the following descriptive answers: not effective at all, somewhat ineffective, neutral, somewhat effective, or very effective.
Time frame: Day 8, Day 15, Day 22
Population: Participants in the Main Subset who received at least one injection with the Avonex Single-use Autoinjector and submitted an assessment form. n=the number of subjects completing the assessment form at the given timepoint. Missing data were not imputed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Avonex Single-Use Autoinjector: Main Subset | Percentage of Participants Who Rated the Avonex Single-use Autoinjector Printed and DVD Training Materials as Very Effective | Printed instructions, Day 8; n=68 | 93 percentage of participants |
| Avonex Single-Use Autoinjector: Main Subset | Percentage of Participants Who Rated the Avonex Single-use Autoinjector Printed and DVD Training Materials as Very Effective | DVD, Day 8; n=69 | 88 percentage of participants |
| Avonex Single-Use Autoinjector: Main Subset | Percentage of Participants Who Rated the Avonex Single-use Autoinjector Printed and DVD Training Materials as Very Effective | Printed instructions, Day 15; n=42 | 90 percentage of participants |
| Avonex Single-Use Autoinjector: Main Subset | Percentage of Participants Who Rated the Avonex Single-use Autoinjector Printed and DVD Training Materials as Very Effective | DVD, Day 15; n=10 | 90 percentage of participants |
| Avonex Single-Use Autoinjector: Main Subset | Percentage of Participants Who Rated the Avonex Single-use Autoinjector Printed and DVD Training Materials as Very Effective | Printed instructions, Day 22; n=24 | 92 percentage of participants |
| Avonex Single-Use Autoinjector: Main Subset | Percentage of Participants Who Rated the Avonex Single-use Autoinjector Printed and DVD Training Materials as Very Effective | DVD, Day 22; n=9 | 89 percentage of participants |
Other Pre-specified
Percentage of Participants With No Erythema, Induration, or Tenderness, and Normal Temperature at the Injection Site After Injection With the Avonex Single-use Autoinjector
The clinician/investigator evaluated the injection site for erythema, induration, and tenderness as none, mild, moderate, or severe after the use of the Avonex single-use autoinjector. Temperature at the injection site was evaluated as normal, warm, or hot. Those participants having no erythema, induration, or tenderness, and normal temperature at the injection site after injection are presented.
Time frame: Day 1, Day 8 through 22 (highest severity reported between Days 8 and 22)
Population: Participants who received at least one injection with the Avonex single-use autoinjector. Missing data were not imputed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Avonex Single-Use Autoinjector: Main Subset | Percentage of Participants With No Erythema, Induration, or Tenderness, and Normal Temperature at the Injection Site After Injection With the Avonex Single-use Autoinjector | No Erythema | 65 percentage of participants |
| Avonex Single-Use Autoinjector: Main Subset | Percentage of Participants With No Erythema, Induration, or Tenderness, and Normal Temperature at the Injection Site After Injection With the Avonex Single-use Autoinjector | No Induration | 86 percentage of participants |
| Avonex Single-Use Autoinjector: Main Subset | Percentage of Participants With No Erythema, Induration, or Tenderness, and Normal Temperature at the Injection Site After Injection With the Avonex Single-use Autoinjector | No Tenderness | 90 percentage of participants |
| Avonex Single-Use Autoinjector: Main Subset | Percentage of Participants With No Erythema, Induration, or Tenderness, and Normal Temperature at the Injection Site After Injection With the Avonex Single-use Autoinjector | Normal Temperature | 100 percentage of participants |
| Avonex Single-Use Autoinjector: Initial Subset | Percentage of Participants With No Erythema, Induration, or Tenderness, and Normal Temperature at the Injection Site After Injection With the Avonex Single-use Autoinjector | Normal Temperature | 100 percentage of participants |
| Avonex Single-Use Autoinjector: Initial Subset | Percentage of Participants With No Erythema, Induration, or Tenderness, and Normal Temperature at the Injection Site After Injection With the Avonex Single-use Autoinjector | No Erythema | 95 percentage of participants |
| Avonex Single-Use Autoinjector: Initial Subset | Percentage of Participants With No Erythema, Induration, or Tenderness, and Normal Temperature at the Injection Site After Injection With the Avonex Single-use Autoinjector | No Tenderness | 79 percentage of participants |
| Avonex Single-Use Autoinjector: Initial Subset | Percentage of Participants With No Erythema, Induration, or Tenderness, and Normal Temperature at the Injection Site After Injection With the Avonex Single-use Autoinjector | No Induration | 100 percentage of participants |