12-week Study to Evaluate RebiSmart™ Suitability for Self Injection in Relapsing Multiple Sclerosis.

Study Overview
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Brief Summary
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The Electronic Device - The RebiSmart™ is an electronic injection device that is being studied for the delivery of Merck Serono's Rebif® New Formulation. The RebiSmart™ device is a stand-alone hand-held device with internal power supply. It is used for subcutaneous (under the skin) injections with single-use sterile disposable needles. The device will be kept in a storage box and placed in the refrigerator after each use. The key features of the RebiSmart™ are as follows: Battery powered electromechanical automatic injector; Automatic needle attachment and detachment; Hidden needle before and after injection; Injection can only be initiated by pressing the injection button when in contact with the skin; Automatic needle insertion and injection of the preset dose into the subcutaneous (under the skin) tissue; Adjustable injection comfort parameters: Injection depth, needle insertion speed, medication injection speed and time that the needle remains in the skin ; Cartridges with 3 doses of Rebif® New Formulation; and Several other electronic functions including history (date and time) of cartridge changes and injections. The Study Drug - Rebif® New Formulation (RNF) Rebif® is a medicine that is part of a family of proteins called interferon beta-1a (IFN-β-1a) molecules that play an important role in the immune system and help limit the damage that occurs with multiple sclerosis (MS). The interferon in Rebif® is like your body's own natural human interferon, but is made outside the body by a process called recombinant DNA technology. Merck Serono International S.A. (the maker of Rebif®) has recently updated the method to make Rebif®, and it is referred to as Rebif® New Formulation (RNF). For the purpose of this study, the form of Rebif® New Formulation (RNF) will differ slightly from the one you currently receive. RNF will be supplied in pre-filled cartridges containing three doses of 44mcg / 0.5 ml IFN-β-1a. This is the amount required for you to administer during the course of one full week of treatment. The dosage of RNF 44mcg is injected under the skin three times per week. The RebiSmart™ device will be provided for the administration of RNF. RNF should be administered, if possible, at the same time (preferably in the late afternoon or evening) on the same three days (e.g. Monday, Wednesday, and Friday), with at least 48 hours break between each administration. You will be asked to record the time and date of each injection in the diary cards provided. You will be taught how to properly use the device to inject the medication. You will also be reminded to rotate injection sites and advised on the importance of avoiding already inflamed areas for future injections. The goals of this research trial are: To evaluate if the electronic device can be used (if it is suitable) by MS patients performing self-injections of Rebif® New Formulation. To determine MS patients overall satisfaction of the new RebiSmart™ device by determining their ease in using it, how often side effects happen (flu-like symptoms, injection site reactions and any other overall injection issues) that they may experience while on the trial. This will be done by completion of the Patient User Trial Questionnaire and the Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ). To evaluate specific features of the RebiSmart™ device from the answers MS patients provide in the User Trial Questionnaire. The MS patient and the person who will trains them on the proper use of the device will complete this questionnaire.

Official Title
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International, Multicenter, Single-arm, Open-label, 12-week Phase IIIb Study to Evaluate RebiSmart™ Suitability for Self Injection of Rebif® New Formulation (RNF) in Multidose Cartridges in Patients With Relapsing Form of Multiple Sclerosis (RMS)

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Drug: Rebif® New Formulation (RNF) using RebiSmartTM


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females between 18 and 65 years of age, inclusive Female subjects must be neither pregnant nor breast-feeding and must lack child-bearing potential, as defined by either: Post-menopausal or surgically sterile, or Using a highly effective method of contraception for the duration of the study. This is defined as a method that result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly, and includes for instance implants, injectables, combined oral contraceptives, intra-uterine device (IUD)s, sexual abstinence or vasectomised partner. Have RMS according to the revised McDonald Criteria 2005 Have disease duration for at least 3 months Are currently receiving RNF 44 mcg sc by Rebiject IITM (RII) tiw and have been consistently on therapy for a minimum of 6 weeks prior to Screening Exclusion Criteria: Have any disease other than MS that could better explain his/her signs and symptoms Receive any other injectable medications on a regular basis during the week prior to the screening period or throughout the duration of the study. The administration of a single injection for treatment or prophylaxis of a condition unrelated to the patient's MS or the patient's RNF therapy (e.g., influenza or pneumococcus vaccination) will be acceptable Receive any MS therapy other than Rebif / RNF (e.g., other disease-modifying drug [DMD]s: immunomodulatory , immunosuppressive agents or combination therapy) within 12 months prior to study enrolment or at any time during the study Receive oral or systemic corticosteroids or adrenocorticotrophic hormone (ACTH) within 30 days prior to SD1 Have inadequate liver function, defined by a alanine aminotransferase (ALT) > 3 x upper limit of normal (ULN), or alkaline phosphatase > 2 x ULN, or total bilirubin > 2 x ULN if associated with any elevation of ALT or alkaline phosphatase Have inadequate bone marrow reserve, defined as a white blood cell count less than 0.5 x lower limit of normal Have moderate to severe renal impairment History of any chronic pain syndrome Any visual or physical impairment that precludes the subject self-injecting the treatment using the RebiSmartä

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: Rebif® New Formulation (RNF) using RebiSmartTM<br>* RNF 44 mg, 3 times a week by subcutaneous injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Number of Subjects Rating the Suitability of RebiSmart at the End of 12-week Treatment Period for Self-injecting Rebif® New Formulation (RNF). | RebiSmart was evaluated as very suitable or suitable; a little suitable; or not suitable at all for self-injecting RNF. The Patient User Trial Questionnaire (UTQ) provides confidence in the ability to evaluate the suitability of the device and ease of understanding the different features of the RebiSmart during the training session and the overall subject impression of the injection administration. Subjects completed the Patient UTQ at Study Day1, Week4, and Week12. The Trainer User UTQ provides confidence in the ability to evaluate the suitability of the RebiSmart by the trainer. | End of 12 week treatment period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Flu Like Symptom (FLS) Score Items 13-16 at End Week 4 | Intention to treat population. MSTCQ FLS Score items 13-16 has a best possible score of 4 and a worst possible score of 20. | at the end of week 4 of treatment | 
| Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Flu Like Symptom (FLS) Score Items 13-16 at End Week 8 | Intention to treat population. MSTCQ FLS Score items 13-16 has a best possible score of 4 and a worst possible score of 20. | at the end of week 8 of treatment | 
| Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Flu Like Symptom (FLS) Score Items 13-16 at End Week 12 | Intention to treat population. MSTCQ FLS Score items 13-16 has a best possible score of 4 and a worst possible score of 20. | at the end of week 12 of treatment | 
| Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Injection Site Reaction Score Items 17-20 at End Week 4 | Intention to treat population. MSTCQ InjectionSite Reaction Score items 17-20 has a best possible score of 4 and a worst possible score of 20. | at the end of week 4 of treatment | 
| Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Injection Site Reaction Score Items 17-20 at End Week 8 | Intention to treat population. MSTCQ InjectionSite Reaction Score items 17-20 has a best possible score of 4 and a worst possible score of 20. | at the end of week 8 of treatment | 
| Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Injection Site Reaction Score Items 17-20 at End Week 12 | Intention to treat population. MSTCQ InjectionSite Reaction Score items 17-20 has a best possible score of 4 and a worst possible score of 20. | at the end of week 12 of treatment | 
| Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Global Side Effects Score Items 21-23 at End Week 4 | Intention to treat population. MSTCQ Global Side Effects Score items 21-23 has a best possible score of 15 and a worst possible score of 3. | at the end of week 4 of treatment | 
| Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Global Side Effects Score Items 21-23 at End Week 8 | Intention to treat population. MSTCQ Global Side Effects Score items 21-23 has a best possible score of 15 and a worst possible score of 3. | at the end of week 8 of treatment | 
| Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Global Side Effects Score Items 21-23 at End Week 12 | Intention to treat population. MSTCQ Global Side Effects Score items 21-23 has a best possible score of 15 and a worst possible score of 3. | at the end of week 12 of treatment | 
| Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Injection Issues Score Item 34 at End Week 4 | Intention to treat population. MSTCQ Injection Issues Score item 34: +5 is the best possible score (much better), -5 is the worst possible score (much worse), zero is neutral (no change) | at the end of week 4 of treatment | 
| Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Injection Issues Score Item 34 at End Week 8 | Intention to treat population. MSTCQ Injection Issues Score item 34: +5 is the best possible score (much better), -5 is the worst possible score (much worse), zero is neutral (no change) | at the end of week 8 of treatment | 
| Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Injection Issues Score Item 34 at End Week 12 | Intention to treat population. MSTCQ Injection Issues Score item 34: +5 is the best possible score (much better), -5 is the worst possible score (much worse), zero is neutral (no change) | at the end of week 12 of treatment | 
| Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Benefit Item 35 at End Week 4 | Intention to treat population. MSTCQ Injection Issues Score item 35 - Most important benefit of the RebiSmart injection system: Fewer injection site reactions; less injection pain; fewer flu-like symptoms; fewer physical side effects; or overall convenience. | at the end of week 4 of treatment | 
| Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Benefit Item 35 at End Week 8 | Intention to treat population. MSTCQ Injection Issues Score item 35 - Most important benefit of the RebiSmart injection system: Fewer injection site reactions; less injection pain; fewer flu-like symptoms; fewer physical side effects; or overall convenience. | at the end of week 8 of treatment | 
| Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Benefit Item 35 at End Week 12 | Intention to treat population. MSTCQ Injection Issues Score item 35 - Most important benefit of the RebiSmart injection system: Fewer injection site reactions; less injection pain; fewer flu-like symptoms; fewer physical side effects; or overall convenience. | at the end of week 12 of treatment | 
| Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Pain Rating Scale Item 37 at End Week 4 | Intention to treat population. MSTCQ Pain Rating Scale item 37. Visual Analogue Scale 0mm (No pain) to 100mm (Worst possible pain) | at the end of week 4 of treatment | 
| Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Pain Rating Scale Item 37 at End Week 8 | Intention to treat population. MSTCQ Pain Rating Scale item 37. Visual Analogue Scale 0mm (No pain) to 100mm (Worst possible pain) | at the end of week 8 of treatment | 
| Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Pain Rating Scale Item 37 at End Week 12 | Intention to treat population. MSTCQ Pain Rating Scale item 37. Visual Analogue Scale 0mm (No pain) to 100mm (Worst possible pain) | at the end of week 12 of treatment | 
| Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Pain Rating Grade Item 38 at End Week 4 | Intention to treat population. MSTCQ Pain Rating Grade item 38. Rated as No pain; Mild; Discomforting; Distressing; or Horrible Excruciating | at the end of week 4 of treatment | 
| Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Pain Rating Grade Item 38 at End Week 8 | Intention to treat population. MSTCQ Pain Rating Grade item 38. Rated as No pain; Mild; Discomforting; Distressing; or Horrible Excruciating | at the end of week 8 of treatment | 
| Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Pain Rating Grade Item 38 at End Week 12 | Intention to treat population. MSTCQ Pain Rating Grade item 38. Rated as No pain; Mild; Discomforting; Distressing; or Horrible Excruciating | at the end of week 12 of treatment | 
| The Incidence of Predefined Injection Site Reactions, MSTCQ Scores, Side Effects, McGill Pain Questionnaire, Visual Analog Scale, and Rating of Pain Regarding Injection Pain Following RNF Administration With RebiSmart at 12-week Treatment Period. | Information on these outcomes is shown separately above, apart from information on the incidence of injection site related adverse events which is shown in the Adverse Events section | at the end of weeks 4, 8, and 12 of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Sclerosis