Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate Efficacy, Safety, and Tolerability of IMU-838 in Patients with Progressive Multiple Sclerosis

Phase 2

Recruiting

Conditions: Multiple Sclerosis
Progressive Multiple Sclerosis
10012303

Registration Number: NL-OMON54447

Lead Sponsor: Immunic AG

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 10

Inclusion Criteria

1. Adult patients, age 18 to 65 years (inclusive).
2. No evidence of relapse in the last 24 months before randomization,
AND
Patients diagnosed with either
a) SPMS, in patients showing evidence of Gd+ MRI lesions (active SPMS) in the
brain or spinal cord, or without Gd+ MRI lesions (non-active SPMS) in the last
12 months, OR
b) PPMS according to 2017 revised McDonald Criteria and the 2013 revised
classification of disease courses with a disease duration of the progressive
disease of <=10 years
3. EDSS score at screening between 3.0 to 6.5 (both inclusive).
4. Evidence of disability worsening not temporarily related to a relapse in the
last 24 months before randomization, adjudicated by a central independent
reviewer, and documented as:
a) An increase of EDSS of at least 1.0 point with Screening EDSS of up to 5.5
(inclusive) and 0.5 point for Screening EDSS 6.0 or 6.5 (as documented in
patient files in the last 24 months before randomization),
OR
b) A 20% worsening (or more) in 25-foot walk time or 9-hole peg test time in
either hand (as documented in patient files in the last 24 months before
randomization),
OR
c) A written summary of the clinical evidence of disability worsening in the
previous 24 months before randomization through a retrospective assessment of
disease worsening from patient files.

5. Female patients:
a) Must be of non-childbearing potential, i.e., 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 at Day 1 (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 of
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 (i.e., 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 [e.g., 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.
6. 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. M

Exclusion Criteria

MS-related exclusion criteria:
1. Any disease other than MS that may better explain the signs and symptoms,
including a history of complete transverse myelitis.
2. Clinical signs or presence of laboratory findings suggestive for
neuromyelitis optica spectrum disorders (NMOSD) or myelin oligodendrocyte
glycoprotein (MOG)-associated encephalomyelitis (i.e., presence of aquaporin-4
antibodies or anti-MOG antibodies).
3. Any MRI finding, atypical for MS, including but not limited to a
longitudinally extensive spinal cord lesion.
4. Any active and uncontrolled coexisting autoimmune disease, other than MS
(except for type 1 diabetes mellitus and inflammatory bowel disease).

Therapy-related exclusion criteria:
5. Any previous or current use of the following MS treatments:
a) alemtuzumab or belimumab, including their biosimilars,
b) cladribine,
c) total lymphoid irradiation, and
d) bone marrow or stem cell transplantation.
6. Any use of the following MS treatments before the date of randomization (see
table in study protocol)
7. Any use of adrenocorticotrophic hormone (ACTH) or occasional use of systemic
corticosteroids (oral or intravenous) 30 days before SV2.
8. Use of any investigational product within 8 weeks or 5× the respective PK
half-life before the date of informed consent, whichever is longer, and
throughout the study. For some investigational products, prolonged biological
effects beyond 8 weeks should be considered.

For more information, please refer to Clinical Study Protocol.

Exclusion Criteria for the OLE Period:
Patients meeting any of the following criteria will be ineligible to
participate in the OLE
Period of the study:
1. Any ongoing, clinically significant (as assessed by the Investigator)
treatment-emergent AE or laboratory abnormality (including bloodbiochemistry
and urinalysis) that can jeopardize the patient's safety, in agreement with the
medical monitor.
2. Significant study or treatment non-compliance (<80% or >125%) during the MT
period, and/or inability or unwillingness to follow instructions by study
personnel.
3. The lack of interpretable BL or EoMT MRI or the omission of more than one
other MRI during the MT.
4. Use of experimental/investigational drug (except for COVID-19 vaccines
approved by emergency use authorization or similar expanded access schemes)
and/or participation in another clinical study of an investigational drug
throughout the duration of the OLE treatment period.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Primary Objective<br /><br>1. Annualized rate of percent brain volume change (PBVC) during MT period<br /><br><br /><br>The primary endpoint will be analyzed on the mITT analysis set. The annualized<br /><br>rate of PBVC between BL and EoMT (or the last available MRI) will be assessed<br /><br>within a random intercept, random slope mixed model, accounting for treatment<br /><br>effect, and stratified for the same factors for which randomization was<br /><br>stratified. The null hypothesis of equal mean slopes of the 2 treatment arms<br /><br>will be tested (at a two-sided 5% level). Sensitivity analyses will be<br /><br>performed to assess the effect of different ICE handling strategies.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Annualized rate of change in BPF during MT period<br /><br><br /><br>Time to 24-week confirmed disability worsening based on expanded disability<br /><br>status scale (EDSS) during the MT period<br /><br><br /><br>Please refer to section 14.3.4.2 of the clinical study protocol for the<br /><br>timepoints of evaluation for the above mentioned secondary end points</p><br>