The purpose of this study is to seek regulatory approval for use of fingolimod in a pediatric population with MS aged 10 to less than 18 years old. This study is conducted in line with the Pediatric Investigational Plan agreed with the EMA (under EU…
ID
Source
Brief title
Condition
- Neurological disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
EDSS, MRI, MS relapses.
Secondary outcome
Adverse events, Physical examination (including skin examination), sexual
development, ophthalmological examination, pulmonology, lab assessments, ECG,
Questionnaires.
Background summary
Fingolimod (FTY720) is an oral drug for the treatment of multiple sclerosis
(MS), it is an immunosupperssivum. Fingolimod reduces the number of activated
T-cells in the blood and in the CNS by the binding to sphingosine-1-phosphate
receptor-1 {S1 P1) on circulating lymphocytes. This binding leads to a
reversible sequestration of T cells, causing auto-aggressive T cells, as it
were in peripheral lymphocyte tissue to be locked, and cannot migrate to sites
of inflammation in the CNS.
Fingolimod gives a reduction of the number of MS relapse rate and leads to an
improvement of the MRI image and of inflammatory markers.
The incidence of pediatric MS is not known, but it is estimated that
approximately 5% (variously estimated range from 0.4 to 10.5%) of MS cases will
manifest in childhood and adolescence, and that less than 2% will do before the
age of 10.
Study objective
The purpose of this study is to seek regulatory approval for use of fingolimod
in a pediatric population with MS aged 10 to less than 18 years old. This study
is conducted in line with the Pediatric Investigational Plan agreed with the
EMA (under EU pediatric regulation (EC) No 1901/2006) and the post-marketing
requirements in the US.
Study design
A study with a duration of 84-month (7 years).
The core phase (maximum 2 years) a double-blind, randomized, active-controlled,
parallel-group multicenter study to evaluate the efficacy and safety of
fingolimod compared to IFN β-1a in children/adolescent patients aged 10-17
(i.e. have not yet had their 18th birthday at randomization) with MS. Followed
by a 5-year open-label extension phase with fingolimod.
The study consists of two phases: a pre-randomization phase consisting of
screening and baseline periods and a double-blind treatment phase.
After obtaining informed consent, patients will enter the screening and
baseline periods of the pre-randomization phase to confirm eligibility for the
study. On Day 1, the first visit in the treatment phase, eligible patients will
be randomized to one of the two treatment arms (fingolimod or IFN β-1a). The
treatment phase will last up to 24 months.
Afterwards, the participant will have the opportunity to be treated for 5 years
with (open label) fingolmod.
Intervention
Treatment with fingolimod or Interferon B 1-a (core phase, maximum 2 years)
followed by treatment with fingolimod (extension phase, 5 years).
Study burden and risks
Risk:
Side effects of study medication.
Burden:
Core Phase:
Study visits: screening, baseline, day 1, 14 and 28, monthly for six months,
then every 3 months.
(Almost) at all visits vital signs, blood test and pregnancy test (only if
relevant).
Monthly (partly home). pregnancy testing for sexually active girls.
Neurological and physical examination every 3 months.
Ophthalmological examination (including OCT measurement) during the first year
every 3 months, then every half year
Lung function tests during screening, M1, 3, 6, and then every six months.
Dermatological examination at the beginning and end of the study.
ECG at screening, day 1, 1 month, then annually.
MRI annually.
X-ray of the left wrist and hand every 6 months.
Completing the C - SSRS (questionnaire to suicidal tendencies) by phone; each
visit except visite M 1.5, 4 and 5.
Completion of Pediatric Quality of Life questionnaire annually.
Extensie fase:
17 visits; 8 visits in first year, as of year 2 twice a year plus 3 months
after End Of Treatment (EOT) visit a Follow-Up (FU) visit.
Pregnancy test (if relevant): monthly (partly at home)
(Almost) at all visits: vital signs, blood collection
Physical examination: 3x in year 1, as of year 2 yearly and at FU visit
X-ray of the left wrist and hand: twice a year (not at EOT ann FU visit)
Skin examination: As of year 1 twice a year and at EOT visit
Ophthalmological examination: Month 3 (v19), month 6, year 1, as of year 2 if
needed and at EOT visit
Lung function tests: Month 2 (v17), month 3, month 6, year 1, as of year 2 if
needed and at EOT visit
ECG: Day 1, month 2, year 1, as of year 2 yearly and at EOT visit
MRI: Month 6, year 1, as of year 2 yearly and at EOT visit
EDSS: As of month 3 at every visit
Completion of C-SSRS: every visit
Completion of Pediatric Quality of Life questionnaire: yearly (not at FU
visit).
Haaksbergweg 16
Amsterdam 1101 BX
NL
Haaksbergweg 16
Amsterdam 1101 BX
NL
Listed location countries
Age
Inclusion criteria
Core phase:
1. Male and female patients aged 10-17 years old, inclusive (i.e., have not yet
had their 18th birthday) at randomization.
2. A diagnosis of MS as defined by the revised consensus definition for
pediatric MS (Krupp et al 2013, Polman et al 2011).
3. Central review of the diagnosis of pediatric MS will be required for all
patients prior to randomization.
4. At least one MS relapse/attack during the previous year or two MS relapses
in the previous two years prior to screening, or evidence of one or more Gd
enhancing lesions on MRI within 6 months prior to randomization (including
screening MRI).
5. Expanded Disability Status Scale (EDSS) score of 0 to 5.5, inclusive.,
Extension Phase:
Criterion applies to all patients entering the Extension Phase;
- Patients that originally met Core Phase Inclusion criteria and completed the
Core phase on or off of study drug.
Criterion applies to patient newly recruited to participate in the Extension
Phase:
Younger cohort is defined as the population of pediatric patients fulfilling
any single one or a combination of the following criteria: being 12 or younger
of age, weighing 40 kg or less, or being pre-pubertal (Tanner stage less than 2)
1. All newly recruited patients* that enroll directly into the Extension Phase
must fulfill
the local country health authority product label approved for pediatric age
group for
inclusion criteria. Countries that do not have the 0.25mg dose formulation of
fingolimod
approved according to local label, may only enroll patients within the younger
cohort who
have a body weight above 40 kg and be prescribed the 0.5mg dose level according
to
local label.
2. Central review (including initial MRI report) of the diagnosis of pediatric
MS
(Thompson et al 2018) will be required for all newly recruited patients.
Exclusion criteria
Core and extension phase:
1. Patients with progressive MS.
2. Patients with widespread and symmetric white matter alterations in the
Screening MRI suggestive of other demyelinating disorders (e.g. metabolic
disorders, mitochondrial disorders).
3. Patients meeting the definition of ADEM (Krupp et al 2013); patients meeting
critieria for neuromyelitis optica (Wingerchuk et al 2006) or tested positive
for aquaporin 4 (AQP4) at Screening. Patients who have tested positive for
anti-MOG (applicable for patients enrolling in the new younger cohort in
extension phase)
4. Patients with active systemic bacterial, viral or fungal infections,
including tuberculosis.
5. Patients without acceptable evidence of immunity to varicella-zoster virus,
mumps, measles, rubella, diphteria, tetanus and pertussis at randomization/
first dose in the extension phase.
6. Patients with any severe cardiac disease or significant findings on the
screening ECG.
7. Positive results of screening period testing for serological markers for
hepatitis A, B, C, and E indicating acute or chronic infection.,
Extension phase:
Criteria apply to patients who completed the Core Phase, but prematurely
discontinued study drug;
- Premature discontinuation of the study drug during the Core Phase due to an
adverse event, serious adverse event, laboratory abnormality or conditions
leading to permanent study drug discontinuation due to safety reasons as
described in the protocol.
- Patients with known new events or concomitant medications that would exclude
them from the Core Phase exclusion criteria.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2011-005677-23-NL |
| ClinicalTrials.gov | NCT01892722 |
| CCMO | NL45701.078.13 |