Raltegravir (Isentress) Pilot Study in Relapsing Multiple Sclerosis (INSPIRE)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2013 by Queen Mary University of London
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Gavin Giovannoni, Queen Mary University of London
ClinicalTrials.gov Identifier:
NCT01767701
First received: January 7, 2013
Last updated: July 12, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention Phase
Relapsing Remitting Multiple Sclerosis
Drug: Raltegravir
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Baseline Versus Treatment Study to Determine the Efficacy of Raltegravir (Isentress) in Preventing Progression of Relapsing Remitting Multiple Sclerosis as Determined by Gadolinium-enhanced MRI

Resource links provided by NLM:


Further study details as provided by Queen Mary University of London:

Primary Outcome Measures:
  • The number of new or recurrent Gd-enhancing lesions that appear on brain T1-weighted MRI [ Time Frame: Baseline and monthly until month 6 post baseline ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The cumulative number of new or enlarging T2 weighted lesions on brain MRI [ Time Frame: Baseline and monthly for 6 months ] [ Designated as safety issue: No ]
  • Change in score on Multiple Sclerosis Functional Composite (MSFC) [ Time Frame: Baseline and monthly until month 6 ] [ Designated as safety issue: No ]
  • Changes in Kurtzke Extended Disability Status Scale (EDSS) score [ Time Frame: Baseline and monthly to month 6 ] [ Designated as safety issue: No ]
  • Cumulative number of Gd-T1 enhancing lesions [ Time Frame: At Baseline and monthly for 6 months ] [ Designated as safety issue: No ]
  • Percent of subjects with scans free from enhancing lesions in Raltegravir treated subjects vs. baseline [ Time Frame: At baseline and monthly for 6 months ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Number of adverse events [ Time Frame: Continuously throughout the study ] [ Designated as safety issue: Yes ]
    This outcome will be assessed by blood, urine and saliva sampling; collection of patient reported symptoms and neurological and physical exams.

  • Severity of adverse events [ Time Frame: Continuously throught the study ] [ Designated as safety issue: Yes ]
    This outcome will be assessed by blood, urine and saliva sampling; collection of patient reported symptoms and neurological and physical exams.


Estimated Enrollment: 24
Study Start Date: April 2013
Estimated Study Completion Date: August 2014
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Raltegravir
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
400mg twice daily for 3 months
Other Name: Isentress

Detailed Description:

There is accumulating research evidence that Human Endogenous Retrovirus (HERV) and herpes viruses (in particular Epstein-Barr Virus) are involved in the pathogenesis of multiple sclerosis. People with active MS have higher levels of HERVs than people either without MS or who have other neurological conditions. It has been shown that HERVs may produce neurotoxic proteins/antigens associated with MS activity and disease progression. This is the first clinical trial investigating the hypothesis that the antiretroviral drug raltegravir may suppress HERV activity and ameliorate progression of relapsing remitting MS. Raltegravir is an integrase inhibitor which blocks retroviral replication. A recent experimental study suggests that raltegravir may also be active against herpes viruses.

Eligible participants (see Inclusion/Exclusion Criteria) will be observed for 3 months having monthly brain Gadolinium enhanced MRIs and blood/urine/saliva sampling (baseline). Then they will be treated with raltegravir (one 400mg pill taken twice a day) for 3 months. During treatment period participants will continue to have monthly MRIs and blood/saliva/urine sampling. Participants will have monthly clinical and neurological examinations and they will complete questionnaires assessing response to treatment. Participants will have screening and study visits at The Royal London Hospital, Whitechapel. Monthly MRIs will be performed at the Institute of Neurology at Queens Square, London.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01767701

Contacts
Contact: Ailsa Weatherall 02078827181 ailsa.weatherall@bartshealth.nhs.uk

Locations
United Kingdom
The Royal London Hospital Recruiting
London, United Kingdom, E1 2AT
Contact: Ailsa Weatherall    02078827181    ailsa.weatherall@bartshealth.nhs.uk   
Principal Investigator: Julian Gold         
Sub-Investigator: Monica Calado-Marta         
Sub-Investigator: Hubert Maruszak         
Sub-Investigator: Klaus Schmierer         
Principal Investigator: Gavin Giovannoni         
Sub-Investigator: Ute-Christiane Meier         
Sub-Investigator: Tove Christensen         
Sponsors and Collaborators
Queen Mary University of London
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Julian Gold, Prof Queen Mary University of London
Principal Investigator: Gavin Giovannoni Queen Mary University of London
  More Information

Additional Information:
Publications:
Responsible Party: Gavin Giovannoni, Professor Gavin Giovannoni, Chair of Neurology, Queen Mary University of London
ClinicalTrials.gov Identifier: NCT01767701     History of Changes
Other Study ID Numbers: 008717QM, 2012-004847-61
Study First Received: January 7, 2013
Last Updated: July 12, 2013
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Queen Mary University of London:
raltegravir
MS
RRMS
Charcot Project

Additional relevant MeSH terms:
Multiple Sclerosis
Multiple Sclerosis, Relapsing-Remitting
Sclerosis
Autoimmune Diseases
Autoimmune Diseases of the Nervous System
Demyelinating Autoimmune Diseases, CNS
Demyelinating Diseases
Immune System Diseases
Nervous System Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on October 29, 2014