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

Relapsing Remitting Multiple Sclerosis Clinical Trial

— PLENO  

Official title:

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™)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03177083
• Other study ID #: PRT-PEG-15-10880
• Secondary ID: 2016-000434-21
• Status: Completed
• Phase: Phase 4
• Start date: January 30, 2017
• Est. completion date: October 26, 2020

Study information

• Verified date: November 2020
• Source: Biogen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: October 26, 2020
• Est. primary completion date: October 26, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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-ß therapy, including IFN-ß-1b 0.25 mg SC every other day or IFN-ß-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

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Relapsing-Remitting
• Relapsing Remitting Multiple Sclerosis
• Sclerosis

Intervention

Drug:
• peginterferon beta-1a
SC every 2 weeks
• interferon beta-1a
Per Summary of Product Characteristics (SMPC)
• interferon beta-1b
Per SMPC

Locations

Country	Name	City	State
Portugal	Hospital Fernando Fonseca	Amadora
Portugal	Hospital de Braga	Braga
Portugal	Centro Hospitalar Cova da Beira	Covilhã
Portugal	Hospital Evora	Evora
Portugal	Hospital Dr. Nelio Mendonça	Funchal
Portugal	Hospital da Senhora da Oliveira	Guimaraes
Portugal	Centro Hospitalar de Leiria	Leiria
Portugal	Centro Hospitalar Lisboa Norte - Hosp Santa Maria	Lisboa
Portugal	Hospital da Luz	Lisboa
Portugal	Hospital Egas Moniz	Lisboa
Portugal	Hospital Beatriz Ângelo, EPE	Loures
Portugal	ULS Matosinhos	Matosinhos
Portugal	Hospital Santo Antonio	Porto
Portugal	Hospital de Sao Sebastiao	Santa Maria da Feira
Portugal	Hospital Viana do Castelo	Viana do Castelo

Sponsors (1)

Lead Sponsor	Collaborator
Biogen

Country where clinical trial is conducted

Portugal, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Combined Counts of Adverse Events (AEs) of Flu-Like Symptoms (FLS)	FLS as defined by chills, pyrexia, myalgia, and asthenia	Up to Week 24
Primary	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
Primary	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
Primary	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	Change in Participant-Reported Treatment Satisfaction Using Treatment Satisfaction Questionnaire for Medication (TSQM-9) in Participants Treated with PLEGRIDY Versus Current SC IFN-ß	A questionnaire assessing patient satisfaction with drug on 3 scales: effectiveness, convenience, and global satisfaction	Baseline to Week 24
Secondary	Change in Participant-Reported Treatment Satisfaction Using TSQM-9 in Participants Who Switched from Current SC IFN-? 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
Secondary	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-?	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
Secondary	Change in PRO Measures in EQ-5D-3L Index in Participants Continuously Treated with PLEGRIDY Versus Participants Who Switched from Current SC IFN-? 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
Secondary	Change in PRO Measures in EQ-5D-3L Index in Participants Who Switched from Current SC IFN-? 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
Secondary	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-?	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
Secondary	Change in PRO Measures in WPAI: MS Score in Participants Continuously Treated with PLEGRIDY Versus Participants Who Switched from Current SC IFN-? 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
Secondary	Change in PRO Measures in WPAI: MS Score in Participants Who Switched from Current SC IFN-? 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
Secondary	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
Secondary	Change in PRO Measures in 12-Item Short Form Survey (SF-12) Score in Participants Treated with PLEGRIDY Versus Current SC IFN-?	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
Secondary	Change in PRO Measures in SF-12 Score in Participants Continuously Treated with PLEGRIDY Versus Participants Who Switched from Current SC IFN-? 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
Secondary	Change in PRO Measures in SF-12 Score in Participants Who Switched from Current SC IFN-? 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
Secondary	Change in PRO Measures in Fatigue Severity Scale (FSS) Score in Participants Treated with PLEGRIDY Versus Current SC IFN-?	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
Secondary	Change in PRO Measures in FSS Score in Participants Continuously Treated with PLEGRIDY Versus Participants Who Switched from Current SC IFN-? 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
Secondary	Change in PRO Measures in FSS Score in Participants Who Switched from Current SC IFN-? 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
Secondary	Change in PRO Measures in Hospital Anxiety And Depression Scale (HADS) Score in Participants Treated with PLEGRIDY Versus Current SC IFN-?	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
Secondary	Change in PRO Measures in HADS Score in Participants Continuously Treated with PLEGRIDY Versus Participants Who Switched from Current SC IFN-? 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
Secondary	Change in PRO Measures in HADS Score in Participants Who Switched from Current SC IFN-? 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
Secondary	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
Secondary	Participants Adherence to Study Treatment as Measured by Returned Injection Pens	Treatment adherence surveillance	Week 24 and Week 72
Secondary	Participants Adherence to Study Treatment as Measured by Treatment Adherence Questionnaire in Participants Who Switched from Current SC IFN-? 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
Secondary	Participants Adherence to Study Treatment as Measured by Returned Injection Pens in Participants Who Switched from Current SC IFN-? Therapy to PLEGRIDY at the End of the Comparator Period	Treatment adherence surveillance	Baseline, Week 24, Week 48 and Week 72
Secondary	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-?	0 mm for all full-dose injections on Visual Analog Scale (VAS) of participant-reported pain.	Week 24
Secondary	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-?	0 mm for all full-dose injections on (VAS) of participant-reported pain.	Week 24
Secondary	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-?	Measured by participant-reported VAS pain score	Week 24
Secondary	Average Change in Participant-Reported VAS Pain Score from Pre-Injection to Immediate Post-Injection in Participants Treated with PLEGRIDY Versus Current SC IFN-?	Measured by participant-reported VAS pain score	Week 24
Secondary	Percentage of Participants with Changes in Relapse Activity	Measured by change of ARR pre-study to on-study ARR	Week 72
Secondary	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
Secondary	Proportion of Relapsed Participants in Overall Population	Proportion of total study participants who experienced a confirmed clinical relapse during the study.	Week 72
Secondary	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-ß	Safety surveillance	Week 24
Secondary	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
Secondary	Percentage of Participants with an AE, Serious AE, and Discontinuation of Study Treatment due to an AE Who Switched from Current SC IFN-? Therapy to PLEGRIDY at the End of the Comparator Period	Safety surveillance	Week 24, Week 48 and Week 72