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

NCT03387046 | Terminated Phase 2 Results

• 1 other identifier: MS200136_0041
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 17

Brief Summary

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.

Conditions

Multiple Sclerosis, Relapsing-Remitting

Keywords

Relapsing remitting multiple sclerosis; D-Aspartate; interferon beta-1a

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Change From Baseline in Multiple Sclerosis Related Disability Measured by Expanded Disability Status Scale (EDSS) at Week 8

  EDSS is an ordinal scale in half-point increments that qualifies disability in participants with Multiple Sclerosis (MS). It assesses the 8 functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel/bladder, cerebral and other) as well as ambulation. EDSS overall score ranging from 0 (normal) to 10 (death due to MS).

  Baseline, Week 8

Secondary Outcomes (9)

• Number of Participants With Change From Baseline in Multiple Sclerosis Related Disability Measured by Expanded Disability Status Scale (EDSS) at Week 12 and 24

  Baseline, Week 12 and 24

• 25-foot Timed Walk (25-FWT) to Measure Multiple Sclerosis Related Disability and Cognitive Impairment

  At Week 8, 12 and 24

• 9 Hole Peg Test (9HPT) to Measure Multiple Sclerosis Related Disability and Cognitive Impairment

  Week 8, 12 and 24

• Symbol Digit Modalities Test to Measure Multiple Sclerosis Related Disability and Cognitive Impairment

  At Week 8, 12 and 24

• Low Contrast Letter Visual Acuity Test to Measure Multiple Sclerosis Related Disability and Cognitive Impairment

  Week 8, 12 and 24

Study Arms (2)

D-aspartate + IFN beta-1a + Methylprednisolone

EXPERIMENTAL

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.

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

Placebo + IFN beta-1a + Methylprednisolone

PLACEBO COMPARATOR

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.

Drug: Placebo; Biological: IFN beta-1a; Drug: Methylprednisolone

Interventions

D-aspartate DIETARY_SUPPLEMENT

D-aspartate 2660 milligram (mg) once daily in the form of oral solution for 24 weeks.

D-aspartate + IFN beta-1a + Methylprednisolone

Placebo DRUG

Placebo matched to D-aspartate once daily in the form of oral solution for 24 weeks.

Placebo + IFN beta-1a + Methylprednisolone

IFN beta-1a BIOLOGICAL

IFN beta-1a was administered subcutaneously at a dose of 44 microgram (mcg) three times a week for 24 weeks.

D-aspartate + IFN beta-1a + Methylprednisolone; Placebo + IFN beta-1a + Methylprednisolone

Methylprednisolone DRUG

Methylprednisolone 1000 mg was administered intravenously once daily for 5 consecutive days.

D-aspartate + IFN beta-1a + Methylprednisolone; Placebo + IFN beta-1a + Methylprednisolone

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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
• MS participants without relapse with clinically stable RR-MS

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck KGaA, Darmstadt, Germany: lead

Study Sites (17)

Ospedale Binaghi, Università di Cagliari,ASL 8

Cagliari, Italy

Location

Ospedale Clinicizzato SS. Annunziata

Chieti, Italy

Location

Azienda Socio Sanitaria Territoriale della Valle Olona (presidio di Gallarate)

Gallarate, Italy

Location

Azienda Ospedaliero Universitaria San Martino

Genova, Italy

Location

Ospedale P.A.Micone

Genova, Italy

Location

Ospedale San Raffaele

Milan, Italy

Location

A.O.U. Federico II

Napoli, Italy

Location

Azienda Ospedaliera di Rilievo Nazionale A. CardarelliAzienda Ospedaliera di Rilievo Nazionale A. Cardarelli

Napoli, Italy

Location

Seconda Università degli Studi di Napoli

Napoli, Italy

Location

Azienda Ospedaliera di Padova

Padua, Italy

Location

I.R.C.C.S. Neuromed-Istituto Neurologico Mediterraneo

Pozzilli, Italy

Location

Azienda Ospedaliera San Camillo Forlanini

Roma, Italy

Location

Azienda Ospedaliera Sant'Andrea-Università di Roma La Sapienza

Roma, Italy

Location

Policlinico Universitario Agostino Gemelli

Roma, Italy

Location

Azienda Ospedaliera Universitaria Policlinico Tor Vergata

Rome, Italy

Location

Ospedale S. Paolo

Savona, Italy

Location

Azienda Ospedaliero Universitaria Ospedali Riuniti

Torrette Di Ancona, Italy

Location

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting

Interventions

D-Aspartic Acid; peginterferon beta-1a; Methylprednisolone

Condition Hierarchy (Ancestors)

Multiple Sclerosis; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Aspartic Acid; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Limitations and Caveats

Study was prematurely terminated, due to slow recruitment rate.

Results Point of Contact

• Title: Communication Center
• Organization: Merck KGaA, Darmstadt, Germany

service@emdgroup.com

+49-6151-72-5200

Study Officials

• Medical Responsible

  Merck KGaA, Darmstadt, Germany

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 22, 2017
• First Posted: December 29, 2017
• Study Start: March 26, 2018
• Primary Completion: January 11, 2019
• Study Completion: January 11, 2019
• Last Updated: February 10, 2020
• Results First Posted: February 10, 2020

Record last verified: 2020-02

Locations

IT (17)