Raltegravir (Isentress) Pilot Study in Relapsing Multiple Sclerosis

NCT01767701 | Completed Phase 2 Results DMC

• 2 other identifiers: 008717QM2012-004847-61
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine whether raltegravir is effective in preventing progression of relapsing remitting multiple sclerosis as determined by gadolinium- enhanced MRI.

Conditions

Relapsing Remitting Multiple Sclerosis

Keywords

raltegravir; MS; RRMS; Charcot Project

Outcome Measures

Primary Outcomes (1)

• The Number of New or Recurrent Gd-enhancing Lesions That Appear on Brain T1-weighted MRI

  Demonstrate in subjects with relapsing remitting multiple sclerosis a reduction in the number of new or recurrent Gd-enhancing lesions that appear on brain T1-weighted MRI over the period of treatment with raltegravir, compared to baseline. Within patient change in number of lesions was calculated by subtracting the after treatment period (3 months) minus before treatment period (3 months).

  Baseline and at 6 months

Secondary Outcomes (5)

• The Cumulative Number of New or Enlarging T2 Weighted Lesions on Brain MRI.

  Baseline and monthly for 6 months

• Change in Score on Multiple Sclerosis Functional Composite (MSFC). This a Composite Score Based on the Measurement of Time in Seconds for the Three Separate Measurements.

  Baseline and monthly until month 6.

• Changes in Kurtzke Extended Disability Status Scale (EDSS) Score

  Baseline and monthly to month 6

• Cumulative Number of Gd-T1 Enhancing Lesions

  At Baseline and monthly for 6 months

• Percent of Subjects With Scans Free From Enhancing Lesions in Raltegravir Treated Subjects vs. Baseline

  Baseline to 6 months

Other Outcomes (2)

• Mean Number of Adverse Events Per Patient

  Screening to six months

• Effect of Raltegravir Therapy on Specific Inflammatory Marker of MS Activity.

  Baseline to 6 months

Study Arms (1)

Raltegravir

EXPERIMENTAL

All eligible patients will complete a 3 months observation period (no medications) followed by 3 months on treatment period. During the treatment period patients will be treated with open label raltegravir 400mg twice daily.

Drug: Raltegravir

Interventions

Raltegravir DRUG

400mg twice daily for 3 months

Also known as: Isentress

Raltegravir

Eligibility Criteria

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

You may qualify if:

• Patients between 18-55 years of age.
• Diagnosis of MS, according to the revised McDonald Criteria 2010.
• EDSS score of 0-6.0 inclusive.
• Documented at least one relapse within the past 12 months or at least one Gd-enhanced lesion on the brain MRI detected within 3 months prior to screening date
• Gd-enhanced lesion on screening MRI (if MRI not used to meet screening criteria above).
• Female patients of childbearing potential will be expected to be on appropriate contraception (hormonal or barrier method of birth control; abstinence) from time of consent until 6 weeks after treatment discontinuation. (the repeated administration of gadolinium and MRI are not recommended during pregnancy). NOTE: Subjects are considered not of child bearing potential if they are surgically sterile (they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal.
• Females of childbearing potential must have a negative urine pregnancy test prior to every MRI scan/ within 7 days prior to being registered for protocol therapy.
• Must give written informed consent and authorize the release and use of protected health information, as required by local law.
• Able and willing to undergo blood, saliva and urine sampling at regular intervals as defined by the protocol.
• Able and willing to receive Gadolinium enhanced MRI's at regular intervals as defined by the protocol.
• Able to comply with study requirements.

You may not qualify if:

• Pregnant or breastfeeding or unwilling to use contraception.
• Treatment with immunosuppressive, immunomodulatory or experimental treatments within the last 6 months of enrolment in the study, but excluding pulsed intravenous or oral steroids for treatment of MS relapse.
• No pulsed intravenous or oral steroids in the 30 days preceding the baseline assessment.
• Patients presenting with medical disorder deemed severe or unstable by the CI such as poorly controlled diabetes or arterial hypertension, severe cardiac insufficiency, unstable ischemic heart disease, abnormal liver function tests (\>2.5 times ULN) and abnormal complete blood count (in particular leukopenia, as defined by a lymphocyte count \<500, neutrophil \<1.5 or platelet count \< 100, or thrombocytopenia \< 1.5 LLN), or any medical condition which, in the opinion of the chief investigator, would pose additional risk to the patient.
• Presence of human immunodeficiency virus antibodies.
• Patients receiving proton pump inhibitors (e.g. omeprazole/esomeprazole)
• Patients with active hepatitis B or/and C with liver function tests \>2.5 times ULN
• Exposure to any other investigational drug within 30 days of enrolment in the study.
• Prior history of malignancy unless an exception is granted by the Chief Investigator.
• History of uncontrolled drug or alcohol abuse within 6 months prior to enrolment into the study.
• Patients treated with Rifampicin in past four weeks.

Sponsors & Collaborators

• Queen Mary University of London: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

The Royal London Hospital

London, E1 2AT, United Kingdom

Location

Related Publications (4)

• Christensen T. HERVs in neuropathogenesis. J Neuroimmune Pharmacol. 2010 Sep;5(3):326-35. doi: 10.1007/s11481-010-9214-y. Epub 2010 Apr 27.

  PMID: 20422298 BACKGROUND

• Perron H, Germi R, Bernard C, Garcia-Montojo M, Deluen C, Farinelli L, Faucard R, Veas F, Stefas I, Fabriek BO, Van-Horssen J, Van-der-Valk P, Gerdil C, Mancuso R, Saresella M, Clerici M, Marcel S, Creange A, Cavaretta R, Caputo D, Arru G, Morand P, Lang AB, Sotgiu S, Ruprecht K, Rieckmann P, Villoslada P, Chofflon M, Boucraut J, Pelletier J, Hartung HP. Human endogenous retrovirus type W envelope expression in blood and brain cells provides new insights into multiple sclerosis disease. Mult Scler. 2012 Dec;18(12):1721-36. doi: 10.1177/1352458512441381. Epub 2012 Mar 28.

  PMID: 22457345 BACKGROUND

• Farrell RA, Antony D, Wall GR, Clark DA, Fisniku L, Swanton J, Khaleeli Z, Schmierer K, Miller DH, Giovannoni G. Humoral immune response to EBV in multiple sclerosis is associated with disease activity on MRI. Neurology. 2009 Jul 7;73(1):32-8. doi: 10.1212/WNL.0b013e3181aa29fe. Epub 2009 May 20.

  PMID: 19458321 BACKGROUND

• Nadal M, Mas PJ, Blanco AG, Arnan C, Sola M, Hart DJ, Coll M. Structure and inhibition of herpesvirus DNA packaging terminase nuclease domain. Proc Natl Acad Sci U S A. 2010 Sep 14;107(37):16078-83. doi: 10.1073/pnas.1007144107. Epub 2010 Aug 30.

  PMID: 20805464 BACKGROUND

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting

Interventions

Raltegravir Potassium

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)

Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Professor Gavin Giovannoni
• Organization: Queen Mary University of London

g.giovannoni@qmul.ac.uk

Study Officials

• Julian Gold, Prof

  Queen Mary University of London

  PRINCIPAL INVESTIGATOR

• Gavin Giovannoni

  Queen Mary University of London

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor Gavin Giovannoni, Chair of Neurology

Study Record Dates

• First Submitted: January 7, 2013
• First Posted: January 14, 2013
• Study Start: April 1, 2013
• Primary Completion: September 1, 2014
• Study Completion: September 1, 2014
• Last Updated: May 30, 2017
• Results First Posted: May 30, 2017

Record last verified: 2017-05

Locations

GB (1)