| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Relapsing Multiple Sclerosis |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 27.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10080700 |
| E.1.2 | Term | Relapsing multiple sclerosis |
| E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
To demonstrate the efficacy of IMU-838 versus placebo in adult patients
with active RMS in delaying the occurrences of relapses based on time to
first relapse (T2FR) |
|
| E.2.2 | Secondary objectives of the trial |
To evaluate the effect of IMU-838 versus placebo on volume of new T2
lesions;
To evaluate the effect of IMU-838 versus placebo on disability
progression;
To evaluate the effect of IMU-838 versus placebo on cognitive
performance;
To evaluate the effect of IMU-838 versus placebo on whole brain
atrophy;
Please refer to the study protocol for further secondary objective. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Main study (DB) inclusion criteria:
1. Male or female patient (age ≥18 to ≤55 years)
2. Patients with an established diagnosis of MS according to 2017
McDonald Criteria
3. Patients with RMS comprising of relapsing remitting MS (RRMS) and active secondary progressive MS, both defined according to Lublin criteria 1996 and 2014. Patients are eligible for this trial if their disease modifying treatment has failed due to
efficacy, safety, or tolerability issues, if they have contraindications or no access to treatment, or if they refuse the offered MS treatment.
4. Active disease as defined by Lublin 2014 evidenced prior to Screening
by:
a.At least 2 relapses(a) in the last 24 months before randomization, or
b.At least 1 relapse(a) in the last 12 months before randomization, or
c.A positive Gd+ MRI scan (brain and/or spine) in the last 12 months
prior to randomization.
(a) Relapses must have been assessed and documented by a physician inthe patient files.
5. EDSS score between 0 and 5.5 (inclusive) at SV1.
Female patients:
a. must be of non-childbearing potential, ie, surgically sterilized
(hysterectomy, bilateral salpingectomy, bilateral oophorectomy at least
6 weeks before SV1) or postmenopausal (where postmenopausal is
defined as no menses for 12 months without an alternative medical
cause), or
b. if of childbearing potential, must have a negative pregnancy test at
SV1 (blood test) and before the first IMP intake (Day 1 blood or urine
test). They must agree not to attempt to become pregnant, must not
donate ova, and must use a highly effective contraceptive method (see
below) together with a barrier method between study consent and 30
days after the last intake of the IMP.
c.highly effective forms of birth control are those with a failure rate less
than 1% per year and include:
i.oral, intravaginal, or transdermal combined (estrogen and progestogen
containing) hormonal contraceptives associated with inhibition of
ovulation.
ii.oral, injectable, or implantable progestogen-only hormonal
contraceptives associated with inhibition of ovulation.
iii.intrauterine device or intrauterine hormone-releasing system.
iv.bilateral tubal occlusion.
v.vasectomized partner (ie, the patient's male partner underwent
effective surgical sterilization before the female patient entered the
clinical study. and is the sole sexual partner of the female patient during
the clinical study).
vi.sexual abstinence (acceptable only if it is the patient's usual form of
birth control/lifestyle choice; periodic abstinence [eg, calendar,
ovulation, symptothermal, postovulation methods] and withdrawal are
not acceptable methods of contraception).
d.Barrier methods of contraception include:
i.condom.
ii.occlusive cap (diaphragm or cervical/vault caps) with spermicidal
gel/film/cream/suppository.
7. Male patients must agree not to father a child or to donate sperm
starting at SV1, throughout the clinical study, and for 30 days after the
last intake of the IMP. Male patients must also:
a. abstain from sexual intercourse with a female partner (acceptable
only if it is the patient's usual form of birth control/lifestyle choice), or
b. use adequate barrier contraception during treatment with the IMP and
until at least 30 days after the last intake of the IMP, and
c. if they have a female partner of childbearing potential, the partner
should use a highly effective contraceptive method as outlined in
inclusion criterion 5.
d. if they have a pregnant partner, they must use condoms while taking
the IMP to avoid exposure of the fetus to the IMP.
8. Willingness and ability to comply with the protocol.
9. Patients are able to read and understand the given
information about the study (including their language capabilities) and provide written informed consent prior to any study-related procedure.
Extension period (OL) inclusion criteria:
1.Completed full visit schedule of the MP up to 72 weeks of (with the
V8/EOMP completed and no more than 1 regular study visit omitted),
independent of the patient's treatment:
a.Double-blind treatment, or
b.Open-label rescue IMU-838 treatment, or
c.Rescue treatment outside this trial (observational phase) but with
double-blind treatment of at least 24 weeks in this trial and approved by
the sponsor.
2.Performed a full and complete Week 72 visit (Visit 8; which also serves
as an EOMP visit and includes the Visit 8 MRI examination). |
|
| E.4 | Principal exclusion criteria |
Main period (DB) exclusion criteria:
1. Patients with non-active secondary progressive MS and primary
progressive MS.
2. Any disease other than MS that may better explain the signs and
symptoms, including history of complete transverse myelitis.
3. Clinical signs or presence of laboratory findings suggestive for
neuromyelitis optica (NMO) spectrum disorders or myelin
oligodendrocyte glycoprotein (MOG)-IgG-associated encephalomyelitis.
4. Any MRI finding, which puts in question the MS diagnosis, including
but not limited to a longitudinally extensive spinal cord lesion.
5. History of malignancy of any organ system (other than localized basal
cell carcinoma of the skin or adequately treated cervical cancer), treated
or untreated, within the past 5 years, regardless of whether there is
evidence of full remission at the current time.
6. Any active and uncontrolled coexisting autoimmune disease, other
than MS (except for type 1 diabetes mellitus and inflammatory bowel
disease).
7. An MS relapse ending within 30 days before SV1 and/or during the
Screening Period (until Day 1).
8. Any corticosteroid treatment for relapse given within 30 days before SV2.
Please refer to protocol for further DB exclusion criteria (Therapy,
immune response, other medical history and concomitant disease as well as general exclusion criteria).
Extension period (OL) exclusion criteria:
1.Any ongoing, clinically significant (as assessed by the investigator)
TEAE (started after intake of IMP) or laboratory abnormality (including
blood chemistry and urinalysis) that, upon discretion of the investigator,
should prohibit further treatment with study medication in this trial(a).
2.Significant treatment non-compliance (defined as having taken <70%
of study medication) or study non-compliance during the MP (as
assessed by the investigator, in consultation with the medical monitor),
and/or inability or unwillingness to follow instructions by study
personnel.
3.Multiple significant protocol deviations during the MP that are
assessed by the investigator, in consultation with the medical monitor,
to negatively affect further patient cooperation in this study.
4.Use of experimental/investigational drug (with the exception of
COVID-19 vaccines approved by emergency use authorization) and/or
participation in another clinical trial of an investigational drug
throughout the duration of the EP open-label treatment period.
(a) If a TEAE(s) is the reason for exclusion from the EP open-label
treatment period, the eligibility can be re-assessed up to 12 weeks
following the last treatment in the MP. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Time to first confirmed relapse, as determined by the Independent Neurology Evaluation Committee (INEC), relapse occurred after the start of treatment administration and before the end of the main period (EOMP), censored at a maximum of 72 weeks, Visit 8 (V8)/EOMP |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| at least 2 weeks, maximum 72 weeks |
|
| E.5.2 | Secondary end point(s) |
Key secondary efficacy:
1)Changes in total volume of new T2-lesions from baseline (BL SV2) MRI
until Week 24 MRI;
2)Time to 12-week confirmed disability worsening (12wCDW)
as assessed on Expanded Disability Status Scale (EDSS);; as
defined in this protocol during the MP (censored until at Week 72/EOMP
visit but with confirmation potentially done within EP, if applicable);
3)Time to confirmed clinically relevant changes in Symbol Digit
Modalities Test (SDMT) in the MP (censored Week 72/EOMP;
4)Annualized rate of percentage changes in whole brain volume from BL
MRI to until V8/EOMP MRI;
Please refer to protocol for secondary efficacy, safety, and exploratory endpoints. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Please refer to section 7 of the clinical study Protocol |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 20 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Algeria |
| Colombia |
| North Macedonia |
| Moldova, Republic of |
| Ukraine |
| Albania |
| Georgia |
| India |
| Jordan |
| Lebanon |
| Mexico |
| Montenegro |
| United States |
| Bulgaria |
| Germany |
| Greece |
| Lithuania |
| Poland |
| Spain |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| LVLS at the end of Extension study |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 9 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 9 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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