Relapsing Remitting Multiple Sclerosis
Conditions
Keywords
Multiple sclerosis, Immunomodulation, Phase 1
Brief summary
Phase 1 study to assess the safety and biological activity of ATX-MS-1467 in patients with relapsing forms of multiple sclerosis. This will be an open label upward dose titration involving injections on 9 occasions, each two weeks apart. After dosing is complete there will be a 22 week follow up period. Blood samples will be drawn throughout the study to monitor safety and the body's response to the injections and MRI scans will be performed on several occasions to follow the course of the multiple sclerosis during the trial.
Interventions
BIOLOGICALATX-MS-1467
Disease specific immune modulating treatment for multiple sclerosis
Sponsors
Aptiv Solutions
ClinStar, LLC
Apitope Technology (Bristol) Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* 1\. Patients who have definite relapsing multiple sclerosis disease as defined by the McDonald criteria (McDonald et al., 2001 and 2005) and as assessed by a neurologist. 2\. HLA DRB1\*15 positive. 3\. High baseline levels of T-cell proliferation in response to myelin basic protein, defined as \>1000 cpm with a \>3 stimulation index compared to background. 4\. Disease duration equal to or less than 10 years (from the first clinical event). 5\. At least one documented relapse in the previous 12 months or two relapses within the previous 24 months prior to screening. 6\. Must be in a clinically stable or improving neurological state during the 28 days preceding Screening. 7\. EDSS score \< 5.5.
Exclusion criteria
* 1\. Subjects treated with β-interferon, plasma exchange, intravenous gamma globulin within the 3 months prior to Study Day 1 2. Subjects treated with glatiramer acetate at any time in the past 3. Subjects who have been treated with parenteral steroids or adrenocorticotropic hormone within 3 months days prior to Study Day 1 4. Prior 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) 5. Prior use of disease related T-cell vaccine or peptide-tolerising agent to treat MS 6. Use of any investigational drug or experimental procedure within 6 months prior to Study Day 1 including cytokine or anti-cytokine therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability | 48 weeks | Occurrence of treatment emergent Adverse Events (AE), Serious Adverse Events, and laboratory abnormalities up to week 48 compared to baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Effect of ATX-MS-1467 on Brain Magnetic Resonance Imaging (MRI). | 16 and 20 weeks | Number of new or persisting Gadolinium-enhancing lesions at week 16 and 20 when compared to baseline. |
Countries
Russia, United Kingdom
Participant flow
Recruitment details
Screening and study procedures were performed at hospital clinics within the United Kingdom and Russian Federation.
Pre-assignment details
Subjects were human lymphocyte antigen (HLA)-DRB1\*15 positive with relapsing-remitting multiple sclerosis as defined by the McDonald criteria and as assessed by a neurologist.
Participants by arm
| Arm | Count |
|---|---|
| Intradermal Injection Injections of ATX-MS-1467 given by the intradermal route | 21 |
| Subcutaneous Injection Injections of ATX-MS-1467 given by the subcutaneous route | 22 |
| Total | 43 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | Subcutaneous Injection | Total | Intradermal Injection |
|---|---|---|---|
| Age, Continuous | 31.6 years | 32.3 years | 33.0 years |
| Region of Enrollment Russian Federation | 20 participants | 34 participants | 14 participants |
| Region of Enrollment United Kingdom | 2 participants | 9 participants | 7 participants |
| Sex: Female, Male Female | 13 Participants | 30 Participants | 17 Participants |
| Sex: Female, Male Male | 9 Participants | 13 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 17 / 21 | 16 / 22 | 7 / 21 | 5 / 22 |
| serious Total, serious adverse events | 1 / 21 | 0 / 22 | 2 / 21 | 1 / 22 |
Outcome results
Primary
Safety and Tolerability
Occurrence of treatment emergent Adverse Events (AE), Serious Adverse Events, and laboratory abnormalities up to week 48 compared to baseline.
Time frame: 48 weeks
Population: The Safety population will be denoted as the 'ITT population' for the summarisation of safety endpoints.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intradermal Injection | Safety and Tolerability | 21 participants |
| Subcutaneous Injection | Safety and Tolerability | 22 participants |
Secondary
The Effect of ATX-MS-1467 on Brain Magnetic Resonance Imaging (MRI).
Number of new or persisting Gadolinium-enhancing lesions at week 16 and 20 when compared to baseline.
Time frame: 16 and 20 weeks
Population: ITT population at week 16 and 20 n=21 (Intradermal injection) ITT population at week 16 and 20 n=22 (Subcutaneous injection) MRI population at week 16 and 20 n=17 (Intradermal injection) MRI population at week 16 and 20 n=20 (Subcutaneous injection)
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Intradermal Injection | The Effect of ATX-MS-1467 on Brain Magnetic Resonance Imaging (MRI). | ITT poulation at baseline | 5.05 MRI lesions |
| Intradermal Injection | The Effect of ATX-MS-1467 on Brain Magnetic Resonance Imaging (MRI). | ITT population at Week 16 | 0.74 MRI lesions |
| Intradermal Injection | The Effect of ATX-MS-1467 on Brain Magnetic Resonance Imaging (MRI). | ITT population at Week 20 | 1.65 MRI lesions |
| Intradermal Injection | The Effect of ATX-MS-1467 on Brain Magnetic Resonance Imaging (MRI). | MRI population at baseline | 3.41 MRI lesions |
| Intradermal Injection | The Effect of ATX-MS-1467 on Brain Magnetic Resonance Imaging (MRI). | MRI population at Week 16 | 0.73 MRI lesions |
| Intradermal Injection | The Effect of ATX-MS-1467 on Brain Magnetic Resonance Imaging (MRI). | MRI population at Week 20 | 1.51 MRI lesions |
| Subcutaneous Injection | The Effect of ATX-MS-1467 on Brain Magnetic Resonance Imaging (MRI). | MRI population at Week 16 | 1.71 MRI lesions |
| Subcutaneous Injection | The Effect of ATX-MS-1467 on Brain Magnetic Resonance Imaging (MRI). | ITT poulation at baseline | 2.09 MRI lesions |
| Subcutaneous Injection | The Effect of ATX-MS-1467 on Brain Magnetic Resonance Imaging (MRI). | MRI population at baseline | 2.3 MRI lesions |
| Subcutaneous Injection | The Effect of ATX-MS-1467 on Brain Magnetic Resonance Imaging (MRI). | ITT population at Week 16 | 1.85 MRI lesions |
| Subcutaneous Injection | The Effect of ATX-MS-1467 on Brain Magnetic Resonance Imaging (MRI). | MRI population at Week 20 | 1.20 MRI lesions |
| Subcutaneous Injection | The Effect of ATX-MS-1467 on Brain Magnetic Resonance Imaging (MRI). | ITT population at Week 20 | 1.47 MRI lesions |
Comparison: Comparison of the baseline 'ITT population' MRI data with week 16 data.p-value: <0.001negative binomial model
Comparison: Comparison of the baseline 'MRI population' data with data from week 16.p-value: 0.03negative binomial model