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Trial record 1 of 1 for:    Raltegravir and multiple sclerosis
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Raltegravir (Isentress) Pilot Study in Relapsing Multiple Sclerosis (INSPIRE)

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ClinicalTrials.gov Identifier: NCT01767701
Recruitment Status : Completed
First Posted : January 14, 2013
Results First Posted : May 30, 2017
Last Update Posted : May 30, 2017
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Gavin Giovannoni, Queen Mary University of London

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Relapsing Remitting Multiple Sclerosis
Intervention Drug: Raltegravir
Enrollment 23
Recruitment Details Patients 18-55 years of age with RRMS, as per McDonald Criteria 2010, EDSS up to 6.0, relapse within the past 12 months or at least one active Gd enhanced lesion on brain MRI within the 3 months prior to consent. All participants were recruited at the Clinical Research Centre of the Royal London Hospital and drawn from greater London.
Pre-assignment Details 31 subjects screened. 8 had no evidence of Gd enhancing lesions in their baseline MRI and were screen failed. Of the 23 participants who were recruited into the study 3 were withdrawn prior to starting the treatment phase; one at the request of the participant and the remaining two due to MS relapse.
Arm/Group Title Raltegravir
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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.

Raltegravir: 400mg twice daily for 3 months

Period Title: Overall Study
Started 20 [1]
Completed 20
Not Completed 0
[1]
All 20 patients who entered the treatment phase completed the six months trial period.
Arm/Group Title Raltegravir
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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.

Raltegravir: 400mg twice daily for 3 months

Overall Number of Baseline Participants 20
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[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants
<=18 years
0
   0.0%
Between 18 and 65 years
20
 100.0%
>=65 years
0
   0.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants
Female
14
  70.0%
Male
6
  30.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United Kingdom Number Analyzed 20 participants
20
1.Primary Outcome
Title The Number of New or Recurrent Gd-enhancing Lesions That Appear on Brain T1-weighted MRI
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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).

Time Frame Baseline and at 6 months
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ITT
Arm/Group Title Raltegravir
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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.

Raltegravir: 400mg twice daily for 3 months

Overall Number of Participants Analyzed 20
Mean (Full Range)
Unit of Measure: lesions
0.12
(-2.67 to 3.33)
2.Secondary Outcome
Title The Cumulative Number of New or Enlarging T2 Weighted Lesions on Brain MRI.
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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.

Time Frame Baseline and monthly for 6 months
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ITT
Arm/Group Title Raltegravir
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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.

Raltegravir: 400mg twice daily for 3 months

Overall Number of Participants Analyzed 20
Mean (Full Range)
Unit of Measure: T2-weighted lesions
0.19
(-4.0 to 5.00)
3.Secondary Outcome
Title 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.
Hide Description 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.
Time Frame Baseline and monthly until month 6.
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ITT
Arm/Group Title Raltegravir
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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.

Raltegravir: 400mg twice daily for 3 months

Overall Number of Participants Analyzed 20
Mean (Standard Deviation)
Unit of Measure: seconds
25 foot walking test in seconds -0.24  (28.2)
9 hole peg test as a timed measurement 0.05  (0.01)
PASAT. This is a TIMED measurement 49.72  (8.81)
4.Secondary Outcome
Title Changes in Kurtzke Extended Disability Status Scale (EDSS) Score
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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).

Time Frame Baseline and monthly to month 6
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All patients enrolled in clinical trial
Arm/Group Title Raltegravir
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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. The EDSS score is determined by the mean score over three months after treatment minus the mean score of the three months before treatment

Raltegravir: 400mg twice daily for 3 months

Overall Number of Participants Analyzed 20
Mean (Standard Deviation)
Unit of Measure: units on a scale
2.55  (0.92)
5.Secondary Outcome
Title Cumulative Number of Gd-T1 Enhancing Lesions
Hide Description 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.
Time Frame At Baseline and monthly for 6 months
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ITT
Arm/Group Title Raltegravir
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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.

Raltegravir: 400mg twice daily for 3 months

Overall Number of Participants Analyzed 20
Mean (Full Range)
Unit of Measure: Gadolinium enhancing T1 lesions
3.08
(0 to 16)
6.Secondary Outcome
Title Percent of Subjects With Scans Free From Enhancing Lesions in Raltegravir Treated Subjects vs. Baseline
Hide Description 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.
Time Frame Baseline to 6 months
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ITT
Arm/Group Title Raltegravir
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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.

Raltegravir: 400mg twice daily for 3 months

Overall Number of Participants Analyzed 20
Measure Type: Number
Unit of Measure: percentage of subjects
15
7.Other Pre-specified Outcome
Title Mean Number of Adverse Events Per Patient
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This outcome will be assessed by blood and urine sampling; collection of patient reported symptoms and neurological and physical exams.

This measure is the total number of adverse events recorded for each type of event during the study period. The number of participants is 31 which is the number screened and enrolled in the study. Eleven participants did not meet the criterion for baseline i.e. having a gadolinium enhancing lesion on MRI at the baseline visit and therefore did not continue to the baseline observation period. The adverse events for the 11 participants who did not begin the study observation period were recorded during the screening period and added to the 20 participants who were studied during the 6 months of the study. Adverse events are recorded as total number during the study period. Each patient may have had more than one adverse event.

Time Frame Screening to six months
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ITT
Arm/Group Title Raltegravir
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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.

Raltegravir: 400mg twice daily for 3 months

Overall Number of Participants Analyzed 31
Mean (Full Range)
Unit of Measure: Adverse events
7.9
(1.0 to 22.0)
8.Other Pre-specified Outcome
Title Effect of Raltegravir Therapy on Specific Inflammatory Marker of MS Activity.
Hide Description Measured by Human C-Reactive Protein (HCRP) which is a measure of general inflammation. The higher the value the more inflammatory response is present. The HCRP was measured monthly for six months. The mean value for the baseline three months was compared with the mean value taken for the second (treatment) three months.
Time Frame Baseline to 6 months
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ITT
Arm/Group Title Raltegravir
Hide Arm/Group Description:

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.

Raltegravir: 400mg twice daily for 3 months

Overall Number of Participants Analyzed 20
Mean (Full Range)
Unit of Measure: ng/mL
535.82
(191.25 to 7397.33)
Time Frame Adverse events were recorded from the time patients signed the informed consent to the end of the study period, which was up to 7 months for each patient, including screening period.
Adverse Event Reporting Description Adverse events were recorded from the time subjects signed the informed consent form. 31 patients signed the informed consent and 20 were eligible for enrollment in the observational and treatment phases of the study. 11 patients were deemed not eligible as they did not have active Gd-enhanced lesions during screening.
 
Arm/Group Title Raltegravir
Hide Arm/Group Description

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.

Raltegravir: 400mg twice daily for 3 months

All-Cause Mortality
Raltegravir
Affected / at Risk (%)
Total   --/--    
Hide Serious Adverse Events
Raltegravir
Affected / at Risk (%) # Events
Total   1/31 (3.23%)    
Nervous system disorders   
MS relapse  [1]  1/31 (3.23%)  1
Indicates events were collected by systematic assessment
[1]
MS relapse requiring hospitalisation for administration of IV methylprednisolone. Normal practise would not be hospital admission but the patient had no care at home and due to MS relapse could care for self at home.
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Raltegravir
Affected / at Risk (%) # Events
Total   31/31 (100.00%)    
Blood and lymphatic system disorders   
Dyslipidemia   10/31 (32.26%)  17
Mycrocytic anemia   1/31 (3.23%)  1
Hypoglycemia   1/31 (3.23%)  1
Normocytic anaemia   1/31 (3.23%)  1
Cardiac disorders   
Hypertension   4/31 (12.90%)  7
Tachycardia   1/31 (3.23%)  2
Hypertension worsening   1/31 (3.23%)  1
Arrhythmia   1/31 (3.23%)  1
Eye disorders   
Visaul fatigue   1/31 (3.23%)  1
Decreased vision   1/31 (3.23%)  1
Stye   1/31 (3.23%)  1
Gastrointestinal disorders   
Gastroenteritis   2/31 (6.45%)  2
Defective gastro-ileal valve   1/31 (3.23%)  1
Bloated abdomen (during antibiotics)   1/31 (3.23%)  1
General disorders   
Headache   10/31 (32.26%)  12
Liver function test abnormal   1/31 (3.23%)  1
Liver function test increased   2/31 (6.45%)  2
Dizziness   3/31 (9.68%)  3
Fall   5/31 (16.13%)  5
Insomnia   2/31 (6.45%)  2
Poor sleep   1/31 (3.23%)  1
Nausea   2/31 (6.45%)  2
Swelling in left arm   1/31 (3.23%)  1
Stomach pain   2/31 (6.45%)  2
Loss of libido   1/31 (3.23%)  1
Pyrexia   1/31 (3.23%)  1
Dysphonia   1/31 (3.23%)  1
Problems concentrating   1/31 (3.23%)  1
Stiff neck   1/31 (3.23%)  1
Fainting   1/31 (3.23%)  1
Vivid dreams   1/31 (3.23%)  1
Tiredness   1/31 (3.23%)  1
Night sweats   1/31 (3.23%)  1
Dry mouth   1/31 (3.23%)  1
Weight loss diet   2/31 (6.45%)  2
Lack of motivation   1/31 (3.23%)  1
Asymptomatic low blood pressure   1/31 (3.23%)  1
Chest pain   1/31 (3.23%)  1
Choking on liquids   1/31 (3.23%)  1
Flushing to face   1/31 (3.23%)  1
Strange sensation when swallowing   1/31 (3.23%)  1
Swelling feelings in fingers   1/31 (3.23%)  1
Immune system disorders   
Adenopathies   2/31 (6.45%)  2
Itchy eyes   1/31 (3.23%)  1
Allergic skin rash worsening   1/31 (3.23%)  1
Hayfever congestion   1/31 (3.23%)  1
Hayfever worsening   1/31 (3.23%)  1
Infections and infestations   
Common cold   14/31 (45.16%)  21
Urinary tract infection   6/31 (19.35%)  8
Sore throat   5/31 (16.13%)  5
Cough   2/31 (6.45%)  2
Sinusitis   3/31 (9.68%)  3
Tooth infection   1/31 (3.23%)  1
Chest infection   1/31 (3.23%)  1
Upper respiratory tract infection   1/31 (3.23%)  1
Injury, poisoning and procedural complications   
Haematoma   2/31 (6.45%)  2
Bruised knee (due to fall)   1/31 (3.23%)  1
Broken toenail   1/31 (3.23%)  1
Cut knee   1/31 (3.23%)  1
Twisted knee   1/31 (3.23%)  1
Hurt wrist   1/31 (3.23%)  1
Musculoskeletal and connective tissue disorders   
Pain   14/31 (45.16%)  17
Pain worsening   2/31 (6.45%)  2
Carpal tunnel syndrome   1/31 (3.23%)  1
Cramps in legs   1/31 (3.23%)  1
Nervous system disorders   
Multiple sclerosis relapse   9/31 (29.03%)  9
Multiple sclerosis sensory relapse   5/31 (16.13%)  6
Sensory disturbance   2/31 (6.45%)  2
Fatigue   4/31 (12.90%)  4
Fatigue increased   4/31 (12.90%)  4
Migraine   4/31 (12.90%)  4
Dysaesthesia worsening   1/31 (3.23%)  1
Nystagmus   1/31 (3.23%)  1
Neuropathic pain   2/31 (6.45%)  2
Tremor in hands   1/31 (3.23%)  1
Numbness (loss of sensation)   3/31 (9.68%)  3
tremor in arms worsened   1/31 (3.23%)  1
Subjective worsening in leg weakness   1/31 (3.23%)  1
Neurologial signs worsening   1/31 (3.23%)  1
Back pain (burning sensation)   1/31 (3.23%)  1
Psychiatric disorders   
Depression   4/31 (12.90%)  4
Depression worsening   1/31 (3.23%)  1
Low mood   1/31 (3.23%)  1
Anxiety   1/31 (3.23%)  1
Panick attacks increased   1/31 (3.23%)  1
Emotional instability   1/31 (3.23%)  1
Renal and urinary disorders   
Bladder dysfunction   3/31 (9.68%)  4
Dysuria   1/31 (3.23%)  1
Bladder problems worsening   3/31 (9.68%)  3
Reproductive system and breast disorders   
Menopause onset   1/31 (3.23%)  1
Erectile dysfunction   1/31 (3.23%)  1
Pelvic mass   1/31 (3.23%)  1
Respiratory, thoracic and mediastinal disorders   
Wheeze   1/31 (3.23%)  1
Skin and subcutaneous tissue disorders   
Itching   2/31 (6.45%)  3
Eczema   1/31 (3.23%)  1
Fungal infection   3/31 (9.68%)  3
Fungal infection worsening   1/31 (3.23%)  1
Dry skin   2/31 (6.45%)  2
Petechial purpura   1/31 (3.23%)  1
Naevus   1/31 (3.23%)  1
Scar from mole removal   1/31 (3.23%)  1
Rash on face   1/31 (3.23%)  1
Mole on toe   1/31 (3.23%)  1
Allergic rash worsening   1/31 (3.23%)  1
Indicates events were collected by systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Professor Gavin Giovannoni
Organization: Queen Mary University of London
EMail: g.giovannoni@qmul.ac.uk
Layout table for additonal information
Responsible Party: Gavin Giovannoni, Queen Mary University of London
ClinicalTrials.gov Identifier: NCT01767701    
Other Study ID Numbers: 008717QM
2012-004847-61 ( EudraCT Number )
First Submitted: January 7, 2013
First Posted: January 14, 2013
Results First Submitted: September 22, 2016
Results First Posted: May 30, 2017
Last Update Posted: May 30, 2017