Study to test IMU-838 in patients with progressive multiple sclerosis

• Register: EUCTR
• Last refreshed on: 19 April 2022
• Main ID: EUCTR2021-000048-23-BG
• Date of registration: 28/09/2021
• Prospective Registration: Yes
• Primary sponsor: Immunic AG
• Public title: Study to test IMU-838 in patients with progressive multiple sclerosis
• Scientific title: Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate Efficacy, Safety, and Tolerability of IMU-838 in Patients with Progressive Multiple Sclerosis - CALLIPER Study
• Date of first enrolment: 28/10/2021
• Target sample size: 450
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2021-000048-23
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Bulgaria, Czechia, Finland, Germany, Hungary, Moldova, Republic of, Netherlands, North Macedonia, Poland, Romania, Russian Federation, Serbia, Ukraine

Contacts

• Name: Dr. Andreas Muehler, CMO
• Affiliation: Immunic AG

• Name: Dr. Andreas Muehler, CMO
• Affiliation: Immunic AG

Key inclusion & exclusion criteria

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 progression 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 progression 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. 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 contra
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 blood biochemistry 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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Progressive forms of Multiple Sclerosis
MedDRA version: 21.1 Level: PT Classification code 10053395 Term: Progressive multiple sclerosis System Organ Class: 10029205 - Nervous system disorders

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Product Name: IMU-838
Pharmaceutical Form: Tablet
INN or Proposed INN: Vidofludimus calcium
CAS Number: 1354012-90-0
Current Sponsor code: IMU-838
Other descriptive name: IM90838
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 45-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Product Name: IMU-838
Pharmaceutical Form: Tablet
INN or Proposed INN: Vidofludimus calcium
CAS Number: 1354012-90-0
Current Sponsor code: IMU-838
Other descriptive name: IM90838
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 22,5-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: To evaluate the efficacy of IMU-838 versus placebo as measured by quantitative magnetic resonance imaging (MRI) analysis for whole brain atrophy in progressive multiple sclerosis (PMS) patients with the Structural Image Evaluation using Normalization of Atrophy (SIENA) method during the Main Treatment (MT) period

Secondary Objective: To evaluate the efficacy of IMU-838 versus placebo as measured by quantitative MRI analysis for whole-brain atrophy in PMS patients with the Structural Image Evaluation using the Brain Parenchymal Fraction (BPF) method during the MT period.

To evaluate the efficacy of IMU-838 compared to placebo in terms of disability worsening during the MT period.

To evaluate the efficacy of IMU-838 compared to placebo in terms of disability and other clinical assessments during the MT period.

To evaluate the efficacy of IMU-838 compared to placebo in terms of MRI parameters during the MT period.

To evaluate the efficacy of IMU-838 compared to placebo in terms of neurofilament light chain (NfL) level.

To evaluate the safety and tolerability of IMU-838 compared to placebo during the MT period and evaluate the long-term safety and tolerability of IMU-838 during the open-label extension (OLE) period.

Primary end point(s): Annualized rate of percent brain volume change (PBVC) during MT period.

Timepoint(s) of evaluation of this end point: The primary endpoint will be analyzed on the mITT analysis set. The annualized rate of PBVC between BL and EoMT (or the last available MRI) will be assessed within a random intercept, random slope mixed model, accounting for treatment effect, and stratified for the same factors for which randomization was stratified. The null hypothesis of equal mean slopes of the 2 treatment arms will be tested (at a two-sided 5% level).
Sensitivity analyses will be performed to assess the effect of different ICE handling strategies.

Secondary Outcome(s)

Secondary end point(s): Annualized rate of change in BPF during MT period

Time to 24-week confirmed disability progression based on expanded disability status scale (EDSS) during the MT period

Timepoint(s) of evaluation of this end point: Please refer to section 14.3.4.2. of clinical study protocol.

Secondary ID(s)

156,314

P2-IMU-838-PMS

Source(s) of Monetary Support

Immunic AG

Ethics review

Status: Approved
Approval date: 28/10/2021
Contact: