Relapsing Remitting Multiple SclerosisPhase 2INSPIRENCT01767701
Raltegravir (Isentress) Pilot Study in Relapsing Multiple Sclerosis
A Phase 2 study testing Raltegravir in people with Relapsing Remitting Multiple Sclerosis, run by Queen Mary University of London at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Relapsing Remitting Multiple Sclerosis
- What is being tested?
- Raltegravir
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Apr 2013to Sep 2014
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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)
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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.
- Conditions
- Relapsing Remitting Multiple Sclerosis
- Being tested
- Raltegravir
- Keywords
- raltegravir, MS, RRMS, Charcot Project
- Medical subject headings
- Multiple Sclerosis, Relapsing-Remitting
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RaltegravirDrug
Also called Isentress
400mg twice daily for 3 months
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Raltegravir |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Baseline and at 6 months
Secondary outcomes (5)
The Cumulative Number of New or Enlarging T2 Weighted Lesions on Brain MRI.
Demonstrate a reduction in the cumulative number of new or enlarging T2 weighted lesions on brain MRI over the period of treatment with Raltegravir compared with baseline.
Within-patient changes in lesion count calculated after-before.
Measured: 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.
Explore preliminary clinical responses in relapsing-remitting multiple sclerosis subjects treated with Raltegravir, compared with baseline as measured by Patient Reported Outcomes (Questionnaires). The MSFC is a composite score consisting of the standardly derived composite score from 9-hole peg test (9HPT), timed walk and PASAT scores. 9HPT is measured as timed speed to complete the task; higher scores indicate less disability. The 25-foot walk is measured as timed speed; higher scores indicate less disability. The Paced Auditory Serial Addition Test (PASAT) The PASAT is a measure of cognitive function that assesses auditory information processing speed and flexibility, as well as calculation ability. It is a timed speed test measured in seconds. In the PASAT a lower score indicates less disability.
Measured: Baseline and monthly until month 6.
Changes in Kurtzke Extended Disability Status Scale (EDSS) Score
The Kurtzke Expanded Disability Status Scale (EDSS) is a method of quantifying disability in multiple sclerosis. The scale has been developed by John F. Kurtzke. The EDSS quantifies disability in eight Functional Systems (FS) and allows neurologists to assign a Functional System Score (FSS) in each of these. 0 = Normal 1-1.5 = No disability, but some abnormal neurological signs 2-2.5 = Minimal disability 3-4.5 = Moderate disability, affecting daily activities, but you can still walk. A lower score indicates less disability.
5-8 = More severe disability, impairing your daily activities and requiring assistance with walking 8.5-9.5 = Very severe disability, restricting you to bed 10 = Death EDSS scores were measured monthly over 6 months and the mean of the measurements for the first three months (baseline) was recorded to use calculate the change from baseline compared with the mean of measurements taken monthly during the second three months (treatment).
Measured: Baseline and monthly to month 6
Cumulative Number of Gd-T1 Enhancing Lesions
This measure is the number of gadolinium-enhancing T1 lesions as determined by MRI taken on the monthly basis during the six months of the study.
Measured: At Baseline and monthly for 6 months
Percent of Subjects With Scans Free From Enhancing Lesions in Raltegravir Treated Subjects vs. Baseline
This measure is the cumulative percentage of subjects who had scans free from Gd enhancing lesions during the first three months (baseline) compared with the second three months (treatment). These percentages are expressed as a total percentage for the baseline and for the treatment periods.
Measured: Baseline to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jan 2013 (estimated)
- Study startApr 2013
- Primary completionSep 2014
- Study completionSep 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Relapsing Remitting Multiple SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Queen Mary University of London
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Principal investigator, Gavin Giovannoni, Queen Mary University of London
- Investigators
- Julian Gold, Prof, Principal investigator, Queen Mary University of LondonGavin Giovannoni, Principal investigator, Queen Mary University of London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01767701
- Sponsor's protocol ID
- 008717QM
- Other IDs
- 2012-004847-61
- Acronym
- INSPIRE
- Status last verified
- May 2017
- First submitted
- 7 Jan 2013
- Last updated
- 30 May 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 20422298Perron 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.
PubMed 22457345Farrell 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.
PubMed 19458321Nadal 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.
PubMed 20805464
Study at a glance
From the registry record, last updated by the sponsor on 30 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01767701
- Acronym / sponsor ID
- INSPIRE / 008717QM
- Conditions
- Relapsing Remitting Multiple Sclerosis
- Keywords
- raltegravir, MS, RRMS, Charcot Project
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Queen Mary University of LondonUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- Apr 2013
- Primary completion
- Sep 2014 (actual)
- Study completion
- Sep 2014 (actual)
- First posted
- 14 Jan 2013 (estimated)
- Results
- Posted 30 May 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Raltegravir | Experimental | Drug: RaltegravirAll 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. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (11 listed)
- 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).
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RaltegravirAlso: Isentress400mg twice daily for 3 months | Drug | Raltegravir |
Primary outcome
The Number of New or Recurrent Gd-enhancing Lesions That Appear on Brain T1-weighted MRI
Time frame: Baseline and at 6 months
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).
5 secondary outcomes
The Cumulative Number of New or Enlarging T2 Weighted Lesions on Brain MRI.
Time frame: 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.
Time frame: Baseline and monthly until month 6.
Changes in Kurtzke Extended Disability Status Scale (EDSS) Score
Time frame: Baseline and monthly to month 6
Cumulative Number of Gd-T1 Enhancing Lesions
Time frame: At Baseline and monthly for 6 months
Percent of Subjects With Scans Free From Enhancing Lesions in Raltegravir Treated Subjects vs. Baseline
Time frame: Baseline to 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 May 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 20422298Christensen T. HERVs in neuropathogenesis. J Neuroimmune Pharmacol. 2010 Sep;5(3):326-35. doi: 10.1007/s11481-010-9214-y. Epub 2010 Apr 27.
- Background: PubMed 22457345Perron 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.
- Background: PubMed 19458321Farrell 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.
- Background: PubMed 20805464Nadal 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Julian Gold, Prof principal investigator
Queen Mary University of London
Gavin Giovannoni principal investigator
Queen Mary University of London
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Raltegravir in people with Relapsing Remitting Multiple Sclerosis, run by Queen Mary University of London at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 May 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Number of New or Recurrent Gd-enhancing Lesions That Appear on Brain T1-weighted MRI (time frame: Baseline and at 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01767701, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 May 2017; AzTrials last refreshed its copy on 28 Oct 2026.