NCT02254304: PROCEED

Effectiveness of Rebif® in Clinically Isolated Syndrome and Relapsing Multiple Sclerosis Using RebiSmart™

Completed Phase 4 Results posted Last updated 30 March 2018

What this trial tests

Phase 4 trial testing Rebif in Relapsing Multiple Sclerosis in 106 participants. Completed in 20 August 2016.

Timeline

31 December 2014

Primary endpoint
20 August 2016

20 August 2016

Quick facts

Lead sponsor	Merck KGaA, Darmstadt, Germany
Phase	Phase 4
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	106
Start date	31 December 2014
Primary completion	20 August 2016
Estimated completion	20 August 2016
Sites	1 location across Germany

Drugs / interventions tested

• Rebif

Conditions studied

• Relapsing Multiple Sclerosis — all drugs for Relapsing Multiple Sclerosis →
• Clinically Isolated Syndrome — all drugs for Clinically Isolated Syndrome →

Sponsor

Merck KGaA, Darmstadt, Germany — full company profile →

Who can join

Adults 18 to 65, any sex, with Relapsing Multiple Sclerosis or Clinically Isolated Syndrome. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Relapse-free RMS Subjects Primary · Month 12

A relapse was defined as the appearance of a new symptom or worsening of an old symptom, attributable to multiple sclerosis (MS), accompanied by an appropriate new neurological abnormality or focal neurological dysfunction lasting at least 24 hours in the absence of fever, and preceded by stability or improvement for at least 30 days. Relapse-free RMS subjects were those who did not had relapse during 12 month treatment period. Data was planned to be reported for "Rebif in RMS Subjects" arm.

Group	Value	95% CI
Rebif In RMS Subjects	66.3

Time to the First Relapse for CIS Subjects Primary · Baseline up to 12 months

A relapse was defined as the appearance of a new symptom or worsening of an old symptom, attributable to MS, accompanied by an appropriate new neurological abnormality or focal neurological dysfunction lasting at least 24 hours in the absence of fever, and preceded by stability or improvement for at least 30 days. Time to the first relapse was defined as the duration from start of the treatment until first relapse. Data was planned to be reported for "Rebif in CIS Subjects" arm.

Group	Value	95% CI
Rebif in CIS Subjects	NA	NA – NA

Percentage of Subjects With Treatment Adherence Secondary · Month 12

According to the World Health Organisation (WHO), treatment adherence is defined as both compliance (taking the medication in the correct dose and according to the schedule prescribed) and persistency (maintenance of the drug regimen over the long-term). Percentage of subjects with treatment adherence under different categories (\<=50%, \>50-75%, \>75-90%, \>90%) were presented.

Adherence <=50%

Group	Value	95% CI
Rebif In RMS Subjects	2.2
Rebif in CIS Subjects	11.8

Adherence >50-75%

Group	Value	95% CI
Rebif In RMS Subjects	2.2
Rebif in CIS Subjects	0.0

Adherence >75-90%

Group	Value	95% CI
Rebif In RMS Subjects	13.5
Rebif in CIS Subjects	0.0

Adherence >90%

Group	Value	95% CI
Rebif In RMS Subjects	80.9
Rebif in CIS Subjects	88.2

Missing

Group	Value	95% CI
Rebif In RMS Subjects	1.1
Rebif in CIS Subjects	0.0

Percentage of Subjects With Relapse by Adherence Category Secondary · Month 12

A relapse was defined as the appearance of a new symptom or worsening of an old symptom, attributable to multiple sclerosis (MS), accompanied by an appropriate new neurological abnormality or focal neurological dysfunction lasting at least 24 hours in the absence of fever, and preceded by stability or improvement for at least 30 days. According to the World Health Organisation (WHO), treatment adherence is defined as both compliance (taking the medication in the correct dose and according to the schedule prescribed) and persistency (maintenance of the drug regimen over the long-term). Percenta

Relapse Status Yes, Adherence <= 50%

Group	Value	95% CI
Rebif In RMS Subjects	0.0
Rebif in CIS Subjects	0.0

Relapse Status Yes, Adherence >50-75%

Group	Value	95% CI
Rebif In RMS Subjects	0.0

Relapse Status Yes, Adherence >75-90%

Group	Value	95% CI
Rebif In RMS Subjects	16.7

Relapse Status Yes, Adherence >90%

Group	Value	95% CI
Rebif In RMS Subjects	19.4
Rebif in CIS Subjects	6.7

Relapse Status Yes, Adherence Missing

Group	Value	95% CI
Rebif In RMS Subjects	0.0

Relapse Status No, Adherence <= 50%

Group	Value	95% CI
Rebif In RMS Subjects	0.0
Rebif in CIS Subjects	50.0

Relapse Status No, Adherence >50-75%

Group	Value	95% CI
Rebif In RMS Subjects	50.0

Relapse Status No, Adherence >75-90%

Group	Value	95% CI
Rebif In RMS Subjects	50.0

Percentage of Subjects Who Prematurely Terminated Treatment and Reasons Secondary · Baseline up to 12 months

Percentage of subjects who prematurely terminated treatment and reasons were presented.

Adverse Event

Group	Value	95% CI
Rebif In RMS Subjects	2.2
Rebif in CIS Subjects	5.9

Lost to follow-up

Group	Value	95% CI
Rebif In RMS Subjects	2.2
Rebif in CIS Subjects	11.8

Protocol Non-compliance

Group	Value	95% CI
Rebif In RMS Subjects	1.1
Rebif in CIS Subjects	0.0

Withdrew Consent

Group	Value	95% CI
Rebif In RMS Subjects	3.4
Rebif in CIS Subjects	0.0

Pain at Injection site and fear of Injection

Group	Value	95% CI
Rebif In RMS Subjects	1.1
Rebif in CIS Subjects	0.0

Personal causes

Group	Value	95% CI
Rebif In RMS Subjects	4.5
Rebif in CIS Subjects	5.9

Personal decision

Group	Value	95% CI
Rebif In RMS Subjects	1.1
Rebif in CIS Subjects	0.0

Mean Number of Relapses in RMS Subjects Secondary · Month 12

A relapse was defined as the appearance of a new symptom or worsening of an old symptom, attributable to multiple sclerosis (MS), accompanied by an appropriate new neurological abnormality or focal neurological dysfunction lasting at least 24 hours in the absence of fever, and preceded by stability or improvement for at least 30 days.

Group	Value	95% CI
Rebif In RMS Subjects	0.2	± 0.54

Number of Subjects With Reasons of Missed Injections Secondary · Baseline up to 12 months

Number of subjects with the reasons of missed injections were presented. Aspartate transaminase and alanine transaminase are abbreviated as ALT and AST respectively. Glutamic oxaloacetic transaminase and glutamic pyruvic transaminase are abbreviated as GOT and GPT respectively.

Forgot to Injection

Group	Value	95% CI
Rebif In RMS and CIS Subjects	48

Tired

Group	Value	95% CI
Rebif In RMS and CIS Subjects	23

Fear of Injection

Group	Value	95% CI
Rebif In RMS and CIS Subjects	11

Did not want to have Injection

Group	Value	95% CI
Rebif In RMS and CIS Subjects	5

Pain at Injection site

Group	Value	95% CI
Rebif In RMS and CIS Subjects	5

Flu-like symptoms

Group	Value	95% CI
Rebif In RMS and CIS Subjects	4

Adverse event

Group	Value	95% CI
Rebif In RMS and CIS Subjects	2

Device broken

Group	Value	95% CI
Rebif In RMS and CIS Subjects	1

Overall Evaluation of RebiSmart Use as Assessed by Investigator Secondary · Month 12

Evaluation of RebiSmart was categorized under very easy, quite easy, Neither easy nor difficult, very difficult and missing

Very easy

Group	Value	95% CI
Rebif In RMS Subjects	46
Rebif in CIS Subjects	13

Quite easy

Group	Value	95% CI
Rebif In RMS Subjects	32
Rebif in CIS Subjects	1

Neither easy nor difficult

Group	Value	95% CI
Rebif In RMS Subjects	9
Rebif in CIS Subjects	1

Quite difficult

Group	Value	95% CI
Rebif In RMS Subjects	0
Rebif in CIS Subjects	0

Very difficult

Group	Value	95% CI
Rebif In RMS Subjects	1
Rebif in CIS Subjects	2

Missing

Group	Value	95% CI
Rebif In RMS Subjects	1
Rebif in CIS Subjects	0

Healthcare Resource Utilization Questionnaire - Number of Visits to Clinic by Subjects Due to Multiple Sclerosis (MS) Secondary · Month 12

Subjects was assessed at Month 12 utilizing the Health Resource Utilization Questionnaire (HRUQ), a subject self-report tool designed to evaluate the economic impact of MS. Healthcare resource utilization was collected in the following areas: admissions and stays in the hospital, emergency room, consultations with specialists, general practitioners, or other healthcare professionals, work productivity, health care financial impact. Number of visits to clinic by subjects due to MS were presented.

Group	Value	95% CI
Rebif In RMS Subjects	0.2	± 0.49
Rebif in CIS Subjects	0.1	± 0.49

Healthcare Resource Utilization Questionnaire - Number of Subjects Visiting Different Types of Doctors During Their Clinical Visit Secondary · Month 12

Subjects was assessed at Month 12 utilizing the Health Resource Utilization Questionnaire (HRUQ), a subject self-report tool designed to evaluate the economic impact of MS. Healthcare resource utilization was collected in the following areas: admissions and stays in the hospital, emergency room, consultations with specialists, general practitioners, or other healthcare professionals, work productivity, health care financial impact. Subjects who took consultations with specialists, general practitioners for MS were presented.

General practitioner

Group	Value	95% CI
Rebif In RMS Subjects	1	± 0.49
Rebif in CIS Subjects	1	± 0.49

Specialist

Group	Value	95% CI
Rebif In RMS Subjects	15
Rebif in CIS Subjects	0

Healthcare Resource Utilization Questionnaire - Number of Visits by Healthcare Professional to Subjects' Home Secondary · Month 12

Subjects was assessed at Month 12 utilizing the Health Resource Utilization Questionnaire (HRUQ), a subject self-report tool designed to evaluate the economic impact of MS. Healthcare resource utilization was collected in the following areas: admissions and stays in the hospital, emergency room, consultations with specialists, general practitioners, or other healthcare professionals, work productivity, health care financial impact. Number of visits by healthcare professional to subjects' home were presented.

Group	Value	95% CI
Rebif In RMS Subjects	0.0	± 0.11
Rebif in CIS Subjects	0.0	± 0.00

Healthcare Resource Utilization Questionnaire - Number of Times Subjects Visited Emergency Room Due to Multiple Sclerosis (MS) Secondary · Month 12

Subjects was assessed at Month 12 utilizing the Health Resource Utilization Questionnaire (HRUQ), a subject self-report tool designed to evaluate the economic impact of MS. Healthcare resource utilization was collected in the following areas: admissions and stays in the hospital, emergency room, consultations with specialists, general practitioners, or other healthcare professionals, work productivity, health care financial impact. Number of times subjects visited emergency room due to MS were presented.

Group	Value	95% CI
Rebif In RMS Subjects	0.0	± 0.00
Rebif in CIS Subjects	0.0	± 0.00

Adverse events — posted to ClinicalTrials.gov

Time frame: Baseline up to 12 months. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Rebif

Serious: 1/106 (1%)

Deaths: —

Serious adverse events (1 terms)

Reaction	System	Rebif
Depression	Psychiatric disorders	—

Other adverse events (2 terms — click to expand)

Reaction	System	Rebif
Influenza Like Illness	General disorders	—
Hepatic Enzyme Increased	Investigations	—

Most-reported serious reactions: Depression.

Data from ClinicalTrials.gov NCT02254304 adverse events section.

Sponsor's own description

This is a Phase 4, interventional, multicenter study of subcutaneous Rebif® (interferon beta-1a) using RebiSmart™ device to assess effectiveness and adherence of treatment in subjects with clinically isolated syndrome (CIS) or relapsing multiple sclerosis (RMS).

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.