A Pilot Study in Participants With Relapsing Remitting Multiple Sclerosis (RR-MS) (INCREASE)

Merck KGaA (EMD Serono)

Status and phase: Terminated; Phase 2

Conditions: Multiple Sclerosis, Relapsing-Remitting

Treatments: Biological: IFN beta-1a; Drug: Methylprednisolone; Drug: Placebo; Dietary Supplement: D-aspartate

Study type: Interventional

Funder types: Industry

Identifiers

NCT03387046

MS200136_0041

Details and patient eligibility

About

The purpose of this study was to evaluate the improvement in spontaneous recovery from clinical deficits at the time of an acute relapse in RR-MS participants already receiving interferon (IFN) beta 1a with D-aspartate (versus placebo) as add-on therapy.

Enrollment: 7 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Participants with RR-MS, according to the revised McDonald Criteria (2010)
• Participants with an expanded disability status scale (EDSS) score between 0 and 3 before screening visit and before relapse
• Participants receiving treatment with IFN beta 1a 44 mcg three times a week for at least 6 months but for no more than 10 years before the screening visit
• Female participants must be neither pregnant nor breastfeeding and must lack childbearing potential
• Participants willing and able to comply with the protocol for the total duration of the study
• Participants able to understand the purposes and the risks of the study
• Participants have signed the appropriate written informed consent form, approved by the Independent Ethics Committee (IEC), prior to the performance of any study activities
• For MS participants with relapse:
• Deterioration of at least one step in a relevant Functional Systems Scale (FSS) or an increase in EDSS of 1 point or more compatible, according to physician's judgment, with the therapy prosecution
• Relapse started within maximum 5 days before the inclusion in the study
• MS participants without relapse with clinically stable RR-MS

Exclusion criteria

• Participants with diagnosis of primary progressive MS (PP-MS)
• Participants have any disease other than MS that could better explain his/her signs and symptoms
• Participants with any comorbidity with diseases that might alter synaptic plasticity (example Parkinson Disease, Alzheimer Disease, Stroke)
• Participants receiving concomitant treatment with drugs that may alter synaptic plasticity (example, cannabinoids)
• Participants with history or presence of any unstable medical condition (tumor or chronic infection or severe life threatening infection within the last 6 months)
• Participants who have received any corticosteroids therapy within 3 months prior to the screening
• Participants with any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressive agents during the course of the study
• Participants who have received any immunosuppressive agents other to corticosteroids, as monotherapy or combination therapy within 3 months prior to the screening visit
• Participants with history or currently active primary or secondary immunodeficiency
• Participants with inadequate liver function, defined by alanine aminotransferase (ALT) > 3 * upper limit of normal (ULN), or alkaline phosphatase (AP) > 2 * ULN, or total bilirubin > 2 * ULN if associated with any elevation of ALT or AP
• Participants with inadequate bone marrow reserve, defined as a white blood cell count less than 0.5 * lower limit of normal (LLN)
• Participants with moderate to severe renal impairment
• Participants unable to complete an magnetic resonance imaging (MRI) (contraindications for MRI include but are not restricted to weight >=140 kilogram (kg), pacemaker, cochlear implants, presence of foreign substances in the eye, intracranial vascular clips, surgery within 6 weeks of entry into the study, coronary stent implanted within 8 weeks prior to the time of the intended MRI, etc)
• Participants with contraindication to gadolinium (Gd) can be enrolled into the study but cannot receive Gd contrast dyes during their MRI scans
• Participants receiving supplements that, in the Investigator's opinion, may affect the evaluation of fatigue
• Participants with any known contraindications or hypersensitivity to D-aspartate or any excipient
• Participants with any other significant disease that in the Investigator's opinion would impede study assessments or endanger the participant
• Female participants with positive pregnancy test at baseline or participants with active project of pregnancy during the study
• Participants with legal incapacity or limited legal capacity
• Participants have participated in any other investigational study within 8 weeks before the screening visit

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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7 participants in 2 patient groups, including a placebo group

D-aspartate + IFN beta-1a + Methylprednisolone

Experimental group

Description:

Participants received D-aspartate 2660 milligrams (mg) once daily in the form of oral solution for 24 weeks along with IFN beta-1a subcutaneously (sc) at a dose of 44 microgram (mcg) three times a week (TIW) in participants without relapse and IFN beta-1a sc TIW plus Methylprednisolone 1000 mg intravenously once daily for 5 consecutive days in participants with relapse.

Treatment:

Biological: IFN beta-1a

Dietary Supplement: D-aspartate

Drug: Methylprednisolone

Placebo + IFN beta-1a + Methylprednisolone

Placebo Comparator group

Description:

Participants received placebo matched to D-aspartate once daily in the form of oral solution for 24 weeks along with IFN beta-1a subcutaneously (sc) at a dose of 44 microgram (mcg) three times a week (TIW) in participants without relapse and IFN beta-1a sc TIW plus Methylprednisolone 1000 mg intravenously once daily for 5 consecutive days in participants with relapse.

Treatment:

Biological: IFN beta-1a

Drug: Placebo

Drug: Methylprednisolone