A Multi-Center, Randomized, Double-Blinded Phase 3 Study to Evaluate the Efficacy, Safety, and Tolerability of IMU-838 versus Placebo in Adults with Relapsing Multiple Sclerosis (ENSURE-2)

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

18 Mar 2022 → ongoing

Decision date (initial)

2024-10-07

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-514619-88-00

EudraCT number

2021-000029-28

ClinicalTrials.gov

NCT05201638

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Pharmacokinetic, Safety

To demonstrate the efficacy of IMU-838 versus placebo in adult patients with RMS in delaying the occurrences of relapses based on time to first relapse (T2FR)

Conditions and MedDRA coding

Relapsing Multiple Sclerosis

Study design 4 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. 1. Male or female patient (age ≥18 to ≤55 years) 2. Patients with an established diagnosis of MS according to 2017 McDonald Criteria [41] 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.
2. 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 and/or Gd+ MRI lesions must have been assessed and documented by a physician in the patient files.
3. 5. EDSS score between 0 and 5.5 (inclusive) at SV1.
4. 6. 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 (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 trial 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 (i.e., the patient's male partner underwent effective surgical sterilization before the female patient entered the clinical trial and is the sole sexual partner of the female patient during the clinical trial). 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. 7. Male patients must agree not to father a child or to donate sperm starting at SV1, throughout the clinical trial, 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.
6. 8. Willingness and ability to comply with the protocol. 9. Patients are able to read and understand the given information about the trial (including their language capabilities) and provide written informed consent prior to any trial-related procedure.
7. Inclusion criteria for the EP: 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.Active treatment option (ATO) within MP, 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).

Exclusion criteria 2

1. Exclusion Criteria for the Main Period of the Trial: 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 exclusion criteria (Therapy, immune response, other medical history and concomitant disease as well as general exclusion criteria).
2. Exclusion Criteria for the EP: 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. 5. Any treatment mentioned in the Therapy Exclusion Criteria 9, 10, 11, 12, and 13. (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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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)

Secondary endpoints 1

1. Key secondary efficacy: 1) Total number of new and / or enlarging T2-MRI lesions from baseline (BL, SV2) until Week 48

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 14

Locations

4 EU/EEA countries · 14 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 121 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