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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Immunic AG

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

20 Dec 2021 → ongoing

Decision date (initial)

2024-09-16

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-514617-35-00

EudraCT number

2021-000048-23

ClinicalTrials.gov

NCT05054140

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Therapy, Efficacy, Safety, Others

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

Conditions and MedDRA coding

Progressive forms of Multiple Sclerosis

Study design 4 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. 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
2. 3. EDSS score at screening between 3.0 to 6.5 (both inclusive)
3. 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.
4. 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.
5. 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 contraception during treatment with the IMP and until at least 30 days after the last intake of the IMP, and Note: Simultaneous use of male and female condoms with or without any other contraception methods is not permitted. c) If they have a female partner of childbearing potential, the partner should use a highly effective contraceptive method as outlined in inclusion criterion 4. d) If they have a pregnant partner, they must use condoms while taking the IMP to avoid exposure of the fetus to the IMP.
6. 7. Willingness and ability to comply with the protocol.
7. 8. Written informed consent given by the patient before the beginning of any study-related procedure. For more information, please refer to Clinical Study Protocol.
8. Inclusion Criteria for the OLE Period 1. Completed 120 weeks of MT period or have confirmed 24-week disability worsening or the patient was in the MT period when the study reached the MT termination event, at which time, the patient could enter the OLE period.

Exclusion criteria 3

1. 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).
2. 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.
3. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Annualized rate of percent brain volume change (PBVC) during MT period.

Secondary endpoints 1

1. Time to 24-week confirmed disability worsening as assessed on a composite of EDSS, 9-Hole Peg Test (9-HPT), or Timed 25-foot Walk (T25-FW) (24wCDW-Comp) during the MT period

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Immunic AG

Sponsor organisation

Immunic AG

Address

Lochhamer Schlag 21, Lochham Lochham

City

Graefelfing

Postcode

82166

Country

Germany

Scientific contact point

Organisation

Immunic AG

Contact name

Andreas Muehler

Public contact point

Organisation

Immunic AG

Contact name

Andreas Muehler

Third parties 21

Locations

6 EU/EEA countries · 41 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 98 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications