An Open-label, One-arm, Proof of Concept Trial to Evaluate the Safety of ATX-MS-1467 (MSC2358825A) and its Effect on Immune Tolerance in Subjects with Relapsing Multiple Sclerosis

• Register: EUCTR
• Last refreshed on: 8 August 2022
• Main ID: EUCTR2013-002916-28-LV
• Date of registration: 16/10/2013
• Prospective Registration: Yes
• Primary sponsor: Merck KGaA
• Public title: An Open-label, One-arm, Proof of Concept Trial to Evaluate the Safety of ATX-MS-1467 (MSC2358825A) and its Effect on Immune Tolerance in Subjects with Relapsing Multiple Sclerosis
• Scientific title: An Open-label, One-arm, Proof of Concept Trial to Evaluate the Safety of ATX-MS-1467 (MSC2358825A) and its Effect on Immune Tolerance in Subjects with Relapsing Multiple Sclerosis
• Date of first enrolment: 12/12/2013
• Target sample size: 20
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-002916-28
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no; Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Latvia, Russian Federation

Contacts

• Name: Communication Center Merck KGaA
• Affiliation: Merck KGaA

• Name: Communication Center Merck KGaA
• Affiliation: Merck KGaA

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male or female out-patients (except where an in-patient stay is required according to standard local practice for lumbar puncture) aged 18 to 65 years of age inclusive at the time of informed consent
2. Willing and able to provide written informed consent and to comply with the requirements of the protocol assessments/procedures
3. Relapsing MS
4. Clinical evidence of recent MS activity defined as either
- at least one documented relapse in the previous 12 months prior to Visit 2, or
- at least two documented relapses in the previous 24 months prior to Visit 2.
5. Radiological activity on Gd-enhanced MRI defined as both
- at least one CEL on MRI at Visit 2, and
- an increase of at least one CEL from Visit 2 to Visit 4, i.e., over the 8-week Baseline Control Period.
6. EDSS score 0-5.5
7. HLA-DRB1*15 positive
8. Neurological stability in the 30 days prior to Visit 5 (Study Day 1)
9. Prior vaccination against tuberculosis (TB)
10. If female, unless post-menopausal (for at least 2 years) or surgically sterilized, must be willing to use two highly effective methods of contraception throughout the entire duration of
the trial and for 90 days following the last dose of ATX-MS-1467
11. If male, must be willing to use two highly effective methods of contraception throughout the entire duration of the trial and for 90 days following the last dose of ATX-MS-1467.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 19
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1

Exclusion criteria:
1. Primary progressive MS
2. Inability to comply with MRI scanning, including contra-indications to MRI such as known allergy to gadolinium contrast dyes, claustrophobia, presence of a pacemaker, cochlear
implants, ferromagnetic devices or clips, intracranial vascular clips, insulin pumps, nerve stimulators
3. Previous treatment with ß-interferon, plasma exchange, intravenous gamma globulin within the 8 weeks prior to Study Day 1 (Visit 5); subjects receiving such treatment at Visit 2 (i.e.,
at the start of the Baseline Control Period) must discontinue treatment and commence washout as soon as it has been confirmed that they are eligible for the trial based on their
Visit 2 MRI scan
4. Previous treatment with steroids (administered via the oral and/or parenteral routes) or adrenocorticotropic hormone within the 30 days prior to the Visit 2 MRI scan; subjects
receiving such treatment at screening (Visit 1) must have completed treatment 30 days prior to the Visit 2 MRI scan
5. Previous treatment with glatiramer acetate
6. Previous treatment with: cytotoxic agents (including but not limited to cladribine, mitoxantrone, cyclophosphamide, azathioprine, methotrexate), fingolimod, laquinimod,
teriflunomide, total lymphoid irradiation, stem cell or bone marrow transplantation, or monoclonal antibody therapy (including natalizumab, daclizumab, alemtuzumab, ocrelizumab)
7. Prior exposure to dimethyl fumurate (BG-12) or dirucotide
8. Prior exposure to any disease-related T cell vaccine or peptide-tolerizing agent for the treatment of MS, including ATX-MS-1467
9. Use of any investigational drug or experimental procedure for MS (including cytokine or anticytokine therapy) within the 30 days prior to screening (Visit 1)
10. Inadequate liver function, defined by aspartate aminotransferase or alanine aminotransferase (ALT) > 3 times the upper limit of normal at screening or at any of the pre-treatment visits (Visits 2-4)
11. Lymphocyte count < 500/µL or neutrophil count < 1500/µL at screening or at any of the pre-treatment visits (Visits 2-4)
12. Major medical illness such as cardiac, endocrinological, hepatic, immunological (other than MS), metabolic, genito-urinary, pulmonary, gastrointestinal, dermatological, or other major
disease that would preclude participation in the trial
13. Known history of active or chronic infectious disease or any disease which compromises immune function (e.g., positive for human immunodeficiency virus, human T-lymphotrophic
virus-1, untreated Lyme disease, untreated TB or hepatic viral disease [hepatitis B and C])
14. Any renal condition that would preclude the administration of gadolinium, e.g., acute or chronic severe renal insufficiency (glomerular filtration rate [GFR] < 30 mL/min/1.73 m2)
15. History of malignancy, including both solid tumor and hematological malignancies, but excluding basal cell and in situ squamous cell carcinomas of the skin that have been excised
and resolved, in situ cervical cancer or prostatic cancer with normal prostatic specific antigen
16. Clinical evidence of severe uncontrolled depression, active suicidal ideation or suicide attempt
17. Any other significant medical or psychiatric conditions that, in the opinion of the Investigator, would preclude participation in the trial or impair the ability to give informed consent
18. Major surgery in the 4 weeks prior to screening (Visit 1)
19. Known hypersensitivity to the trial medication or diluents
20. Participa

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

Health Condition(s) or Problem(s) studied

Relapsing Multiple Sclerosis
MedDRA version: 20.0 Level: PT Classification code 10067063 Term: Progressive relapsing multiple sclerosis System Organ Class: 10029205 - Nervous system disorders

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

Intervention(s)

Product Name: ATX-MS-1467
Product Code: MSC2358825A
Pharmaceutical Form: Solution for injection/infusion
INN or Proposed INN: MSC2304479A
CAS Number: 1147979-29-0
Current Sponsor code: ATX-MS-01
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 200-
INN or Proposed INN: MSC2304480A
CAS Number: 1147979-31-4
Current Sponsor code: ATX-MS-04
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 200-
INN or Proposed INN: MSC2304481A
CAS Number: 1147979-32-5
Current Sponsor code: ATX-MS-06
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 200-
INN or Proposed INN: MSC2304482A
CAS Number: 1147979-30-3
Current Sponsor code: ATX-MS-07
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 200-

Primary Outcome(s)

Secondary Objective: - To evaluate the effects of ATX-MS-1467 administered intradermally, titrated to a dose of 800 µg biweekly, for a total period of 20 weeks on other MRI parameters
- To evaluate the effects of ATX-MS-1467 administered intradermally, titrated to a dose of 800 µg biweekly, for a total period of 20 weeks on clinical parameters
- To evaluate the safety of ATX-MS-1467 administered intradermally, titrated to a dose of 800 µg biweekly, for a total period of 20 weeks

Main Objective: The primary objective of the trial is to evaluate the effects of ATX-MS-1467 administered intradermally, titrated to a dose of 800 µg every 2 weeks (biweekly), for a total period of 20 weeks on 1.5T MRI parameters compared to a Baseline Control Period off treatment in subjects with relapsing MS.

Primary end point(s): The primary endpoint is the change in the average number of T1 CEL at the last three on-treatment scans (Weeks 12, 16 and 20) compared to the average number of T1 CEL at the three baseline scans (Visits, 2, 3 and 4).

Timepoint(s) of evaluation of this end point: Weeks 2, 3, 4, 12, 16 and 20

Secondary Outcome(s)

Secondary end point(s): - Total number of T1 CEL at each scheduled post-baseline MRI visit
- Change from baseline (average of the three baseline scans, Visits 2, 3 and 4) in total number of T1 CEL at each scheduled post-baseline MRI visit
- Change from baseline (average of the three baseline scans, Visits 2, 3 and 4) in total volume of T1 CEL at each scheduled post-baseline MRI visit
- Total number of new or newly enlarging T2 lesions at each scheduled post-baseline MRI visit
- Change from Visit 4 in total number of T1 CEL at each scheduled post-baseline MRI visit
- Change from Visit 4 in total volume of T1 CEL at each scheduled post-baseline MRI visit
- Mean ARR at Week 20
- Time to first relapse
- Change from baseline in total EDSS score at Week 20
- Change from baseline in total MSFC score at Week 20
- Nature, frequency and severity of TEAEs
- Frequency and severity of ISRs
- Vital signs, physical examination, clinical laboratory variables, and ECGs, as well as the frequency and timing of premature termination from the trial.

Timepoint(s) of evaluation of this end point: Wweeks 2, 3, 4 and 20

Secondary ID(s)

EMR200166-001

Source(s) of Monetary Support

Merck KGaA

Ethics review

Status: Approved
Approval date: 01/11/2013
Contact:

Results

• Results available: Yes
• Date Posted: 17/03/2017
• Date Completed: 11/04/2016
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2013-002916-28/results