Evaluate Safety/Tolerability in Portuguese Participants With RRMS Transitioning From Current Therapy (PLENO)

Open-label, Randomized, 2-arm, Active Comparator Study to Evaluate Safety and Tolerability in Portuguese Patients With Relapsing Remitting Multiple Sclerosis (MS) Transitioning From Current Subcutaneous Interferon Therapy to Peginterferon Beta 1a (PLEGRIDY™)

The primary objective of the study is to evaluate safety and tolerability as defined by the frequency of the adverse events (AEs) of flu-like symptoms (FLS) [chills, pyrexia, myalgia, and asthenia], injection site reactions (ISRs), and injection site reaction pain (ISR-P), over 24 weeks of treatment (the active comparator period) with PLEGRIDY 125 microgram (μg) subcutaneous (SC) every 2 weeks versus current SC IFN-β therapy in participants with Relapsing Remitting Multiple Sclerosis (RRMS).

Study Overview

• Status: Completed
• Conditions: Relapsing Remitting Multiple Sclerosis
• Intervention / Treatment: Drug: peginterferon beta-1a; Drug: interferon beta-1a; Drug: interferon beta-1b

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 4

Contacts and Locations

Study Locations

• Portugal
  • Amadora, Portugal, 2720-276
    • Hospital Fernando Fonseca
  • Braga, Portugal, 4710-243
    • Hospital de Braga
  • Covilhã, Portugal, 6200-251
    • Centro Hospitalar Cova da Beira
  • Evora, Portugal, 7000-811
    • Hospital Évora
  • Funchal, Portugal, 9004-514
    • Hospital Dr. Nelio Mendonça
  • Guimaraes, Portugal, 4835-044
    • Hospital da Senhora da Oliveira
  • Leiria, Portugal, 2410-197
    • Centro Hospitalar de Leiria
  • Lisboa, Portugal, 1500-650
    • Hospital da Luz
  • Lisboa, Portugal, 1349-019
    • Hospital Egas Moniz
  • Lisboa, Portugal, 1649-035
    • Centro Hospitalar Lisboa Norte - Hosp Santa Maria
  • Loures, Portugal, 2674-514
    • Hospital Beatriz Ângelo, EPE
  • Matosinhos, Portugal, 4464-513
    • ULS Matosinhos
  • Porto, Portugal, 4099-001
    • Hospital Santo Antonio
  • Santa Maria da Feira, Portugal, 4520-211
    • Hospital de Sao Sebastiao
  • Viana do Castelo, Portugal, 4904-858
    • Hospital Viana do Castelo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• A confirmed diagnosis of RRMS, as defined by McDonald criteria (2017).
• An EDSS score between 0 and 5.0.
• All female participants of childbearing potential must practice effective contraception during the study and be willing and able to continue contraception for 3 months after their last dose of study treatment.
• On continual treatment for ≥6 months with a single current SC IFN-β therapy, including IFN-β-1b 0.25 mg SC every other day or IFN-β-1a 22 μg or 44 μg SC 3 times weekly

Key Exclusion Criteria:

• Known history of human immunodeficiency virus.
• Known history of or positive test result for antibodies to hepatitis C, or current hepatitis B infection (defined as positive for hepatitis B surface antigen [HBsAg] and/or positive for hepatitis B core antibody [HBcAb]) at Screening. Participants with immunity to hepatitis B from either active vaccination (defined as negative HBsAg, positive hepatitis B surface antibody [HBsAb], and negative HBcAb) or from previous natural infection (defined as negative HBsAg, positive HBsAb immunoglobulin G, and positive HBcAb) are eligible to participate in the study (definitions are based on the Centers for Disease Control and Prevention's interpretation of the hepatitis B serology panel [CDC 2007]).
• An MS relapse that has occurred within the 50 days prior to randomization and/or lack of stabilization from a previous relapse prior to randomization (Day 1).
• Any previous treatment with PLEGRIDY.

NOTE: Other protocol defined Inclusion/Exclusion may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: peginterferon beta-1a	Drug: peginterferon beta-1a; SC every 2 weeks; Other Names: PLEGRIDY, BIIB017
Active Comparator: Current Therapy	Drug: interferon beta-1a; Per Summary of Product Characteristics (SMPC); Other Names: Rebif; Drug: interferon beta-1b; Per SMPC; Other Names: Betaferon, Extavia

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Combined Counts of Adverse Events (AEs) of Flu-Like Symptoms (FLS)	FLS as defined by chills, pyrexia, myalgia, and asthenia	Up to Week 24
Combined Counts of AEs of Injection Site Reactions (ISRs)	Defined as a post-application assessment score ≥2 in participant assessments using the Patient's Erythema Self-Assessment 1 (PSA) scale	Up to Week 24
Combined Counts of AEs of Injection Site Reactions (ISRs)	Defined as a post-application assessment score ≥2 in clinician assessments using the Clinician Erythema Assessment (CEA) scale	Up to Week 24
Combined Counts of AEs of ISR Pain (ISRP)	Defined as visual analog scale (VAS) associated with ISR ≥1 immediately after injection or 30 minutes post-injection	Up to Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Participant-Reported Treatment Satisfaction Using Treatment Satisfaction Questionnaire for Medication (TSQM-9) in Participants Treated with PLEGRIDY Versus Current SC IFN-β	A questionnaire assessing patient satisfaction with drug on 3 scales: effectiveness, convenience, and global satisfaction	Baseline to Week 24
Change in Participant-Reported Treatment Satisfaction Using TSQM-9 in Participants Who Switched from Current SC IFN-Β Therapy to PLEGRIDY at the End of the Comparator Period	A questionnaire assessing patient satisfaction with drug on 3 scales: effectiveness, convenience, and global satisfaction	Week 24 and Week 48
Change in Participant-Reported Outcome (PRO) Measures in EuroQol Group 5-Dimension 3-Level Version (EQ-5D-3L) Index in Participants Treated with PLEGRIDY Versus Current SC IFN-Β	The EQ-5D-3L is a standardized instrument for use as a measure of health outcome. It is a health questionnaire that consists of the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D-3L descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, extreme problems.	Baseline and Week 24
Change in PRO Measures in EQ-5D-3L Index in Participants Continuously Treated with PLEGRIDY Versus Participants Who Switched from Current SC IFN-Β Therapy to PLEGRIDY at the End of the Comparator Period	The EQ-5D-3L is a standardized instrument for use as a measure of health outcome. It is a health questionnaire that consists of the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D-3L descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, extreme problems.	Week 24, Week 48 and Week 72
Change in PRO Measures in EQ-5D-3L Index in Participants Who Switched from Current SC IFN-Β Therapy to PLEGRIDY at the End of the Comparator Period	The EQ-5D-3L is a standardized instrument for use as a measure of health outcome. It is a health questionnaire that consists of the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D-3L descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, extreme problems.	Baseline, Week 24, Week 48 and Week 72
Change in PRO Measures in Work Productivity and Activity Impairment Questionnaire: Multiple Sclerosis V2.1 (WPAI: MS) Score in Participants Treated with PLEGRIDY Versus Current SC IFN-Β	The Work Productivity and Activity Impairment (WPAI) questionnaire is a validated instrument to measure impairments in work and activities. The WPAI yields four types of scores: 1. Absenteeism (work time missed) 2. Presenteesism (impairment at work / reduced on-the-job effectiveness) 3. Work productivity loss (overall work impairment / absenteeism plus presenteeism) 4. Activity Impairment. WPAI outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity.	Baseline and Week 24
Change in PRO Measures in WPAI: MS Score in Participants Continuously Treated with PLEGRIDY Versus Participants Who Switched from Current SC IFN-Β Therapy to PLEGRIDY at the End of the Comparator Period	The Work Productivity and Activity Impairment (WPAI) questionnaire is a validated instrument to measure impairments in work and activities. The WPAI yields four types of scores: 1. Absenteeism (work time missed) 2. Presenteesism (impairment at work / reduced on-the-job effectiveness) 3. Work productivity loss (overall work impairment / absenteeism plus presenteeism) 4. Activity Impairment. WPAI outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity.	Week 24, Week 48 and Week 72
Change in PRO Measures in WPAI: MS Score in Participants Who Switched from Current SC IFN-Β Therapy to PLEGRIDY at the End of the Comparator Period	The Work Productivity and Activity Impairment (WPAI) questionnaire is a validated instrument to measure impairments in work and activities. The WPAI yields four types of scores: 1. Absenteeism (work time missed) 2. Presenteesism (impairment at work / reduced on-the-job effectiveness) 3. Work productivity loss (overall work impairment / absenteeism plus presenteeism) 4. Activity Impairment. WPAI outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity.	Baseline, Week 24, Week 48 and Week 72
Percentage of Participants with Changes in Clinical Status Assessed Using the Expanded Disability Status Scale (EDSS)	The EDSS measures disability status on a scale ranging from 0 to 10, with higher scores indicating more disability. Scoring is based on measures of impairment in eight functional systems on examination by a neurologist.	Week 48
Change in PRO Measures in 12-Item Short Form Survey (SF-12) Score in Participants Treated with PLEGRIDY Versus Current SC IFN-Β	A short form survey with 12 questions selected from the SF-36 Health Survey. The questions are weighted and summed to create two scales on physical and mental functioning. Physical Composite Scores (PCS) and Mental Composite Scores (MCS) range from 0 to 100, where a zero indicates the lowest level of health and 100 indicates the highest level of health.	Baseline and Week 24
Change in PRO Measures in SF-12 Score in Participants Continuously Treated with PLEGRIDY Versus Participants Who Switched from Current SC IFN-Β Therapy to PLEGRIDY at the End of the Comparator Period	A short form survey with 12 questions selected from the SF-36 Health Survey. The questions are weighted and summed to create two scales on physical and mental functioning. Physical Composite Scores (PCS) and Mental Composite Scores (MCS) range from 0 to 100, where a zero indicates the lowest level of health and 100 indicates the highest level of health.	Week 24, Week 48 and Week 72
Change in PRO Measures in SF-12 Score in Participants Who Switched from Current SC IFN-Β Therapy to PLEGRIDY at the End of the Comparator Period	A short form survey with 12 questions selected from the SF-36 Health Survey. The questions are weighted and summed to create two scales on physical and mental functioning. Physical Composite Scores (PCS) and Mental Composite Scores (MCS) range from 0 to 100, where a zero indicates the lowest level of health and 100 indicates the highest level of health.	Baseline, Week 24, Week 48 and Week 72
Change in PRO Measures in Fatigue Severity Scale (FSS) Score in Participants Treated with PLEGRIDY Versus Current SC IFN-Β	A 9-item questionnaire that measures the severity of fatigue and functionality. Each question is scored on a scale of 1 to 7, where 1 equals strongly disagree and 7 equals strongly agree. A higher total score indicates greater fatigue severity and impairment.	Baseline and Week 24
Change in PRO Measures in FSS Score in Participants Continuously Treated with PLEGRIDY Versus Participants Who Switched from Current SC IFN-Β Therapy to PLEGRIDY at the End of the Comparator Period	A 9-item questionnaire that measures the severity of fatigue and functionality. Each question is scored on a scale of 1 to 7, where 1 equals strongly disagree and 7 equals strongly agree. A higher total score indicates greater fatigue severity and impairment.	Week 24, Week 48 and Week 72
Change in PRO Measures in FSS Score in Participants Who Switched from Current SC IFN-Β Therapy to PLEGRIDY at the End of the Comparator Period	A 9-item questionnaire that measures the severity of fatigue and functionality. Each question is scored on a scale of 1 to 7, where 1 equals strongly disagree and 7 equals strongly agree. A higher total score indicates greater fatigue severity and impairment.	Baseline, Week 24, Week 48 and Week 72
Change in PRO Measures in Hospital Anxiety And Depression Scale (HADS) Score in Participants Treated with PLEGRIDY Versus Current SC IFN-Β	A 14-item self-rating scale that assesses anxiety and depression. Each question is scored on a scale ranging from 0 to 3. Responses are summed to provide separate scores for anxiety and depression that range from 0 to 21. For each corresponding subscale, a total score of 0-7 equals normal, 8-10 equals borderline case, and 11-21 equals case.	Baseline and Week 24
Change in PRO Measures in HADS Score in Participants Continuously Treated with PLEGRIDY Versus Participants Who Switched from Current SC IFN-Β Therapy to PLEGRIDY at the End of the Comparator Period	A 14-item self-rating scale that assesses anxiety and depression. Each question is scored on a scale ranging from 0 to 3. Responses are summed to provide separate scores for anxiety and depression that range from 0 to 21. For each corresponding subscale, a total score of 0-7 equals normal, 8-10 equals borderline case, and 11-21 equals case.	Week 24, Week 48 and Week 72
Change in PRO Measures in HADS Score in Participants Who Switched from Current SC IFN-Β Therapy to PLEGRIDY at the End of the Comparator Period	A 14-item self-rating scale that assesses anxiety and depression. Each question is scored on a scale ranging from 0 to 3. Responses are summed to provide separate scores for anxiety and depression that range from 0 to 21. For each corresponding subscale, a total score of 0-7 equals normal, 8-10 equals borderline case, and 11-21 equals case.	Baseline, Week 24, Week 48 and Week 72
Participants Adherence to Study Treatment as Measured by Treatment Adherence Questionnaire	A questionnaire assessing adherence and the reasons for not taking drug at the recommended frequency of administration.	Week 24 and Week 72
Participants Adherence to Study Treatment as Measured by Returned Injection Pens	Treatment adherence surveillance	Week 24 and Week 72
Participants Adherence to Study Treatment as Measured by Treatment Adherence Questionnaire in Participants Who Switched from Current SC IFN-Β Therapy to PLEGRIDY at the End of the Comparator Period	A questionnaire assessing adherence and the reasons for not taking drug at the recommended frequency of administration.	Baseline, Week 24, Week 48 and Week 72
Participants Adherence to Study Treatment as Measured by Returned Injection Pens in Participants Who Switched from Current SC IFN-Β Therapy to PLEGRIDY at the End of the Comparator Period	Treatment adherence surveillance	Baseline, Week 24, Week 48 and Week 72
Proportion of Pain-Free Participants Immediately After Injection (Defined as 0 mm for All Full-Dose Injections on VAS of Participant-Reported Pain) at End Of the Comparator Period in Participants Treated with PLEGRIDY Versus Current SC IFN-Β	0 mm for all full-dose injections on Visual Analog Scale (VAS) of participant-reported pain.	Week 24
Proportion of Pain-Free Participants 30 Minutes after Injection (Defined as 0 mm for All Full-Dose Injections on VAS of Participant-Reported Pain) at End of the Comparator Period in Participants Treated with PLEGRIDY Versus Current SC IFN-Β	0 mm for all full-dose injections on (VAS) of participant-reported pain.	Week 24
Average Change in Participant-Reported VAS Pain Score from Pre-Injection to 30 Minutes Post-Injection in Participants Treated with PLEGRIDY Versus Current SC IFN-Β	Measured by participant-reported VAS pain score	Week 24
Average Change in Participant-Reported VAS Pain Score from Pre-Injection to Immediate Post-Injection in Participants Treated with PLEGRIDY Versus Current SC IFN-Β	Measured by participant-reported VAS pain score	Week 24
Percentage of Participants with Changes in Relapse Activity	Measured by change of ARR pre-study to on-study ARR	Week 72
Annualized Relapse Rate (ARR) in Participants in the Overall Population	Calculated by dividing the total number of participant relapses by the total number of participant years at risk.	Week 72
Proportion of Relapsed Participants in Overall Population	Proportion of total study participants who experienced a confirmed clinical relapse during the study.	Week 72
Percentage of Participants with an Adverse Event (AE), Serious AE, and Discontinuations of Study Treatment due to an AE in Participants Treated with PLEGRIDY Versus Current SC IFN-β	Safety surveillance	Week 24
Percentage of Participants with an AE, Serious AE, and Discontinuation of Study Treatment due to an AE Continuously Treated with PLEGRIDY	Safety surveillance	Week 24, Week 48 and Week 72
Percentage of Participants with an AE, Serious AE, and Discontinuation of Study Treatment due to an AE Who Switched from Current SC IFN-Β Therapy to PLEGRIDY at the End of the Comparator Period	Safety surveillance	Week 24, Week 48 and Week 72

Collaborators and Investigators

• Sponsor: Biogen

Study record dates

Study Major Dates

• Study Start (Actual): January 30, 2017
• Primary Completion (Actual): October 26, 2020
• Study Completion (Actual): October 26, 2020

Study Registration Dates

• First Submitted: January 26, 2017
• First Submitted That Met QC Criteria: June 1, 2017
• First Posted (Actual): June 6, 2017

Study Record Updates

• Last Update Posted (Actual): November 25, 2020
• Last Update Submitted That Met QC Criteria: November 23, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Physiological Effects of Drugs; Anti-Infective Agents; Antiviral Agents; Antineoplastic Agents; Immunologic Factors; Adjuvants, Immunologic; Interferons; Interferon beta-1a; Interferon-beta; Interferon beta-1b
• Other Study ID Numbers: PRT-PEG-15-10880; 2016-000434-21 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No