Multiple Sclerosis (MS), Relapsing Remitting Multiple Sclerosis
Conditions
Keywords
Autoimmune, Multiple Sclerosis (MS), Relapsing Remitting MS
Brief summary
A safety study of ANK-700 in patients with relapsing remitting multiple sclerosis. The study has two parts: Part A - first in human study in which patients receive a single dose of ANK-700 Part B - patients will receive three doses of either ANK-700 or placebo
Detailed description
Study ANK-700-01 is a Phase 1, FIH study designed to evaluate the safety and tolerability of ANK-700 in patients with relapsing remitting multiple sclerosis (rrms). An overview of the two parts and proposed dose groups is given below: Part A (SAD): Patients will receive a single dose of ANK-700. Part B (MAD): Patients will receive three doses of either ANK-700 or placebo.
Interventions
DRUGANK-700
Intravenous (IV) infusion
DRUGPlacebo
Intravenous (IV) infusion
Sponsors
Anokion SA
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosed with RRMS per revised McDonald criteria (2017) with an EDSS score ≤ 6.5 at screening * Neurologically stable with no evidence of relapse within the 28 days before signing the informed consent form (ICF) * Either not currently receiving disease modifying MS therapy, or currently using fumarate drugs (dimethyl fumarate or diroximel fumarate) * Patients must use a highly effective method of birth control or are sterile or postmenopausal as confirmed by study Investigator * Patient has signed and understands the ICF
Exclusion criteria
* Diagnosis of primary progressive MS or secondary progressive MS * Uncontrolled or significant medical conditions (including active infection or chronic hepatitis) which, in the opinion of the Investigator, preclude participation * Patients treated with glatiramer acetate, parenteral steroids or adrenocorticotropic hormone, β-interferon, plasma exchange within the 3 months prior to first dose * Patients treated with sphingosine-1-phospate receptor modulators such as fingolimod, ozanimod, or siponimod within 6 months prior to first dose * Patients treated with cytotoxic agents (including, but not limited to, cladribine, mitoxantrone, cyclophosphamide, azathioprine, and methotrexate), laquinimod, teriflunomide, or IV gamma globulin within 12 months prior to first dose * Patients treated with monoclonal antibody therapy (including natalizumab, daclizumab, rituximab, ofatumumab, and ocrelizumab) within 24 months prior to first dose * Patients previously treated with alemtuzumab, total lymphoid irradiation, mesenchymal stem cell or hematopoietic stem cell transplantation, or tolerance-inducing therapies for MS * Contraindication to or inability to undergo gadolinium-enhanced magnetic resonance imaging (MRI) scan * Use of any investigational drug or experimental procedure within previous 6 months that would interfere with the assessment of ANK-700 * Patients who are pregnant or breastfeeding * Patients receiving any vaccination within 28 days prior to first dose * Patient does not agree to limit alcohol intake to 2 drink equivalents or less per day during the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Up to 1 year | Incidence and severity of treatment-emergent adverse events (TEAEs) as assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 or higher |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CMAX | Days 1 and 7: One PK sample was taken pre-dose (≥at least 5 min prior to infusion), with all subsequent PK samples taken after end of infusion at the following time points: 0 min, 7min, 15min, 30min, 1h, 2h, 3h, 4h, 6h, 8h | Geometric mean of maximum plasma concentration (Cmax) |
| AUC Last | Days 1 and 7: One PK sample was taken pre-dose (≥at least 5 min prior to infusion), with all subsequent PK samples taken after the end-of-infusion at the following time points: 0 min, 7 min, 15min, 30 min, 1h, 2h, 3h, 4h, 6h, 8h | Area under the plasma concentration-time curve from time 0 to the last measurable time point (AUC last) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Part A SAD Cohort 2, 1.0 mg/kg ANK-700 All enrolled patients will receive one dose of 1.0 mg/kg ANK-700
ANK-700: Intravenous (IV) infusion | 3 |
| Part A SAD Cohort 1, 0.3 mg/kg ANK-700 All enrolled patients will receive one dose of 0.3 mg/kg ANK-700
ANK-700: Intravenous (IV) infusion | 3 |
| Part A SAD Cohort 3, 3.0 mg/kg ANK-700 All enrolled patients will receive one dose of 3.0 mg/kg ANK-700
ANK-700: Intravenous (IV) infusion | 3 |
| Part B MAD Cohort 4, 0.3 mg/kg ANK-700 All enrolled patients will receive three doses of 0.3 mg/kg ANK-700
ANK-700: Intravenous (IV) infusion | 9 |
| Part B MAD Cohort 5, 1.0 mg/kg ANK-700 All enrolled patients will receive three doses of 1.0 mg/kg ANK-700
ANK-700: Intravenous (IV) infusion | 8 |
| Part B MAD Cohort Placebo All enrolled patients will receive three doses of Placebo
Placebo: Intravenous (IV) infusion | 8 |
| Total | 34 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Part A SAD Cohort 1, 0.3 mg/kg ANK-700 | Total | Part A SAD Cohort 2, 1.0 mg/kg ANK-700 | Part B MAD Cohort Placebo | Part B MAD Cohort 5, 1.0 mg/kg ANK-700 | Part B MAD Cohort 4, 0.3 mg/kg ANK-700 | Part A SAD Cohort 3, 3.0 mg/kg ANK-700 |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 34 Participants | 3 Participants | 8 Participants | 8 Participants | 9 Participants | 3 Participants |
| Age, Continuous | 50.3 years STANDARD_DEVIATION 6.43 | 48.2 years STANDARD_DEVIATION 8.18 | 47.0 years STANDARD_DEVIATION 7 | 44 years STANDARD_DEVIATION 9.59 | 50.9 years STANDARD_DEVIATION 7.49 | 49.1 years STANDARD_DEVIATION 8.43 | 48.7 years STANDARD_DEVIATION 9.87 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 3 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Missing | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Mixed | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 3 Participants | 29 Participants | 1 Participants | 8 Participants | 7 Participants | 7 Participants | 3 Participants |
| Region of Enrollment United States | 3 participants | 34 participants | 3 participants | 8 participants | 8 participants | 9 participants | 3 participants |
| Sex: Female, Male Female | 0 Participants | 24 Participants | 1 Participants | 6 Participants | 7 Participants | 7 Participants | 3 Participants |
| Sex: Female, Male Male | 3 Participants | 10 Participants | 2 Participants | 2 Participants | 1 Participants | 2 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 9 | 0 / 8 | 0 / 8 |
| other Total, other adverse events | 2 / 3 | 1 / 3 | 3 / 3 | 9 / 9 | 6 / 8 | 6 / 8 |
| serious Total, serious adverse events | 1 / 3 | 0 / 3 | 0 / 3 | 1 / 9 | 1 / 8 | 0 / 8 |
Outcome results
Primary
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Incidence and severity of treatment-emergent adverse events (TEAEs) as assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 or higher
Time frame: Up to 1 year
Population: All patients who received any amount of study drug with treatment group based on the dose level received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A SAD Cohort 1, 0.3 mg/kg ANK-700 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TEAE | 2 Participants |
| Part A SAD Cohort 1, 0.3 mg/kg ANK-700 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Grade 3 or higher TEAE | 1 Participants |
| Part A SAD Cohort 1, 0.3 mg/kg ANK-700 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | SAE | 1 Participants |
| Part A SAD Cohort 1, 0.3 mg/kg ANK-700 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | no TEAE | 1 Participants |
| Part A SAD Cohort 2, 1.0 mg/kg ANK-700 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | SAE | 0 Participants |
| Part A SAD Cohort 2, 1.0 mg/kg ANK-700 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Grade 3 or higher TEAE | 0 Participants |
| Part A SAD Cohort 2, 1.0 mg/kg ANK-700 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TEAE | 1 Participants |
| Part A SAD Cohort 2, 1.0 mg/kg ANK-700 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | no TEAE | 2 Participants |
| Part A SAD Cohort 3, 3.0 mg/kg ANK-700 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | no TEAE | 0 Participants |
| Part A SAD Cohort 3, 3.0 mg/kg ANK-700 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | SAE | 0 Participants |
| Part A SAD Cohort 3, 3.0 mg/kg ANK-700 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Grade 3 or higher TEAE | 0 Participants |
| Part A SAD Cohort 3, 3.0 mg/kg ANK-700 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TEAE | 3 Participants |
| Part B MAD Cohort 4, 0.3 mg/kg ANK-700 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TEAE | 9 Participants |
| Part B MAD Cohort 4, 0.3 mg/kg ANK-700 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | no TEAE | 0 Participants |
| Part B MAD Cohort 4, 0.3 mg/kg ANK-700 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Grade 3 or higher TEAE | 3 Participants |
| Part B MAD Cohort 4, 0.3 mg/kg ANK-700 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | SAE | 1 Participants |
| Part B MAD Cohort 5, 1.0 mg/kg ANK-700 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | SAE | 1 Participants |
| Part B MAD Cohort 5, 1.0 mg/kg ANK-700 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | no TEAE | 2 Participants |
| Part B MAD Cohort 5, 1.0 mg/kg ANK-700 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Grade 3 or higher TEAE | 1 Participants |
| Part B MAD Cohort 5, 1.0 mg/kg ANK-700 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TEAE | 6 Participants |
| Part B MAD Cohort Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Grade 3 or higher TEAE | 1 Participants |
| Part B MAD Cohort Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | SAE | 0 Participants |
| Part B MAD Cohort Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | no TEAE | 2 Participants |
| Part B MAD Cohort Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TEAE | 6 Participants |
Secondary
AUC Last
Area under the plasma concentration-time curve from time 0 to the last measurable time point (AUC last)
Time frame: Days 1 and 7: One PK sample was taken pre-dose (≥at least 5 min prior to infusion), with all subsequent PK samples taken after the end-of-infusion at the following time points: 0 min, 7 min, 15min, 30 min, 1h, 2h, 3h, 4h, 6h, 8h
Population: PK Analysis Set (PKAS) included all enrolled patients who received ≥ 1 complete dose of study drug and had ≥ 1 pre-dose and 1 post-dose measurement.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Part A SAD Cohort 1, 0.3 mg/kg ANK-700 | AUC Last | Day 1 | NA h*ng/mL |
| Part A SAD Cohort 2, 1.0 mg/kg ANK-700 | AUC Last | Day 1 | 3620 h*ng/mL |
| Part A SAD Cohort 3, 3.0 mg/kg ANK-700 | AUC Last | Day 1 | NA h*ng/mL |
| Part B MAD Cohort 4, 0.3 mg/kg ANK-700 | AUC Last | Day 1 | 309 h*ng/mL |
| Part B MAD Cohort 4, 0.3 mg/kg ANK-700 | AUC Last | Day 7 | 217 h*ng/mL |
| Part B MAD Cohort 5, 1.0 mg/kg ANK-700 | AUC Last | Day 7 | 887 h*ng/mL |
| Part B MAD Cohort 5, 1.0 mg/kg ANK-700 | AUC Last | Day 1 | 1620 h*ng/mL |
Secondary
CMAX
Geometric mean of maximum plasma concentration (Cmax)
Time frame: Days 1 and 7: One PK sample was taken pre-dose (≥at least 5 min prior to infusion), with all subsequent PK samples taken after end of infusion at the following time points: 0 min, 7min, 15min, 30min, 1h, 2h, 3h, 4h, 6h, 8h
Population: PK Analysis Set (PKAS) included all enrolled patients who received ≥ 1 complete dose of study drug and had ≥ 1 pre-dose and 1 post-dose measurement.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Part A SAD Cohort 1, 0.3 mg/kg ANK-700 | CMAX | Day 1 | NA ng/mL |
| Part A SAD Cohort 2, 1.0 mg/kg ANK-700 | CMAX | Day 1 | 7120.7 ng/mL |
| Part A SAD Cohort 3, 3.0 mg/kg ANK-700 | CMAX | Day 1 | NA ng/mL |
| Part B MAD Cohort 4, 0.3 mg/kg ANK-700 | CMAX | Day 1 | 800.28 ng/mL |
| Part B MAD Cohort 4, 0.3 mg/kg ANK-700 | CMAX | Day 7 | 540.99 ng/mL |
| Part B MAD Cohort 5, 1.0 mg/kg ANK-700 | CMAX | Day 7 | 1942.2 ng/mL |
| Part B MAD Cohort 5, 1.0 mg/kg ANK-700 | CMAX | Day 1 | 3816 ng/mL |