Phase 1
Completed N=28
Safety and Tolerability Study of MEDI-551, a B-cell Depleting Agent, to Treat Relapsing Forms of Multiple Sclerosis
Multiple Sclerosis, Relapsing Forms
Source: ClinicalTrials.gov NCT01585766 ↗
Enrolled (actual)
28
Serious AEs
14.3%
Results posted
Oct 2018
Primary outcomePrimary: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) — 6; 5; 3; 3 Participants
Summary
The purpose of this study is to evaluate the safety and tolerability of ascending intravenous (IV) and subcutaneous (SC) doses of MEDI-551 in adult subjects with relapsing forms of multiple sclerosis (MS).
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Treatment-Emergent Adverse Events (TEAEs) |
6; 5; 3; 3; 3; 6 | — |
| PRIMARY Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs) |
1; 1; 0; 0; 1; 1 | — |
| PRIMARY Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs |
1; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Vital Sign Abnormalities Reported as TEAEs |
1; 0; 1; 0; 0; 2 | — |
| SECONDARY Time to Reach Maximum Observed Serum Concentration (Tmax) of MEDI-551 |
0.14; 2.98; 0.07; 7.92; 0.12 | — |
| SECONDARY Maximum Observed Serum Concentration (Cmax) of MEDI-551 |
17.9; 6.67; 43.1; 24.7; 248 | — |
| SECONDARY Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC 0-last) of MEDI-551 |
436; 197; 1140; 788; 6850 | — |
| SECONDARY Area Under the Plasma Concentration-time Curve From Zero to Infinity (AUC 0-infinity) of MEDI-551 |
440; 201; 1150; 794; 6950 | — |
| SECONDARY Dose Normalized Area Under the Plasma Concentration-time Curve From Zero to Infinity (AUC 0-infinity/D) of MEDI-551 |
7.34; 3.35; 5.75; 2.65; 5.79 | — |
| SECONDARY Clearance of MEDI-551 |
139; 351; 181; 457; 180 | — |
| SECONDARY Terminal Elimination Half-life (t1/2) of MEDI-551 |
17.7; 12.3; 17.7; 15.1; 18.7 | — |
| SECONDARY Absolute Subcutaneous Bioavailability (F%) of MEDI-551 |
58; 46 | — |
| SECONDARY Absolute CD20 B-cell Count at Baseline |
190; 173; 180; 183; 366; 201 | — |
| SECONDARY Time to 90 Percent (%) CD20 B-cell Depletion |
15.0; 88.0; 25.0; 15.0; 14.5 | — |
| SECONDARY Duration of Suppression Greater Than or Equal to 90 % of CD20 B-cell Count |
149; 100; 180; 211; 254 | — |
| SECONDARY Maximum Change From Baseline in Absolute CD20 of Peripheral Blood B-cell Count to LTFU |
25.0; 99.8; 99.2; 99.7; 99.8; 99.8 | — |
| SECONDARY Number of Participants Positive for Anti-Drug Antibodies to MEDI-551 |
0; 0; 0; 0; 0; 0 | — |
Eligibility Criteria
Inclusion Criteria
- Confirmed relapsing form of MS (ie, RRMS, SPMS, PRMS, or CIS) according to revised 2010 McDonald criteria and MRI brain lesions consistent with MS on screening
- At least 1 documented relapse within the past 3 years prior to screening
- EDSS between 0.0 and 6.5 at screening
- Have no more than 20 Gd-enhancing T1 brain lesions detected by cranial MRI scan
Exclusion Criteria
- Subjects with impaired renal function
- Major surgery within 8 weeks of the screening visit
- Subjects who are unable to undergo cranial MRI scan
- A history of hypersensitivity to Gd-containing MRI contrast agents
- Has received within 1 year prior to screening: monoclonal antibodies, experimental B-cell depleting agents, or treatment with natalizumab (Tysabri) for greater than 3 months
- Receiving monthly methylprednisone or equivalent glucocorticoid for disease modification of a relapsing form of MS
- Known sensitivity to acetaminophen/paracetamol, diphenhydramine or equivalent antihistamine, methylprednisolone or equivalent glucocorticoid, or to any component of the investigational drug
- Diagnosis of PPMS, neuromyelitis optica, or other non-MS variant of neuro-inflammatory or demyelinating diseases
- Any history of opportunistic infection or the presence of active infection within two months prior to screening or any herpes zoster infection that has not resolved within 12 weeks prior to screening
- Any clinically significant findings during the screening phase, including physical, neurological, laboratory, or ECG examination as per protocol
Data sourced from ClinicalTrials.gov (NCT01585766). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.