Clinical trial NCT01585766: Safety and Tolerability Study of MEDI-551, a B-cell Depleting Agent, to Treat Relapsing Forms of Multiple Sclerosis
Official title: A Phase 1 Randomized Study of MEDI-551 in Subjects With Relapsing Forms of Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Multiple Sclerosis, Relapsing Forms
Keywords: MAb, B cell, depletion, RMS
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2012-04-26
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).

Detailed description: This is a Phase 1, multicenter, multinational, randomized, blinded, placebo-controlled, dose-escalation study to evaluate the safety and tolerability of IV and SC doses of MEDI-551 in adult subjects with relapsing forms of MS.

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

Primary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: From study drug administration (Day 1) through the end of treatment period (Day 169)
measure: Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs)
timeFrame: From study drug administration (Day 1) through the long term follow up period (up to 18 months after early discontinuation visit or 24 week treatment period).
measure: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs
timeFrame: From study drug administration (Day 1) through the end of treatment period (Day 169)
measure: Number of Participants With Vital Sign Abnormalities Reported as TEAEs
timeFrame: From study drug administration (Day 1) through the end of treatment period (Day 169)
Secondary outcomes:
measure: Time to Reach Maximum Observed Serum Concentration (Tmax) of MEDI-551
timeFrame: Predose (Day 1) and Postdose (IV Cohorts only), Days 4 (SC Cohorts only), 8, 15 Predose and Postdose (IV Cohorts only), 29, 57, 85, 113, 141, and 169
measure: Maximum Observed Serum Concentration (Cmax) of MEDI-551
timeFrame: Predose (Day 1) and Postdose (IV Cohorts only), Days 4 (SC Cohorts only), 8, 15 Predose and Postdose (IV Cohorts only), 29, 57, 85, 113, 141, and 169
measure: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC 0-last) of MEDI-551
timeFrame: Predose (Day 1) and Postdose (IV Cohorts only), Days 4 (SC Cohorts only), 8, 15 Predose and Postdose (IV Cohorts only), 29, 57, 85, 113, 141, and 169
measure: Area Under the Plasma Concentration-time Curve From Zero to Infinity (AUC 0-infinity) of MEDI-551
timeFrame: Predose (Day 1) and Postdose (IV Cohorts only), Days 4 (SC Cohorts only), 8, 15 Predose and Postdose (IV Cohorts only), 29, 57, 85, 113, 141, and 169
measure: Dose Normalized Area Under the Plasma Concentration-time Curve From Zero to Infinity (AUC 0-infinity/D) of MEDI-551
timeFrame: Predose (Day 1) and Postdose (IV Cohorts only), Days 4 (SC Cohorts only), 8, 15 Predose and Postdose (IV Cohorts only), 29, 57, 85, 113, 141, and 169
measure: Clearance of MEDI-551
timeFrame: Predose (Day 1) and Postdose (IV Cohorts only), Days 4 (SC Cohorts only), 8, 15 Predose and Postdose (IV Cohorts only), 29, 57, 85, 113, 141, and 169
measure: Terminal Elimination Half-life (t1/2) of MEDI-551
timeFrame: Predose (Day 1) and Postdose (IV Cohorts only), Days 4 (SC Cohorts only), 8, 15 Predose and Postdose (IV Cohorts only), 29, 57, 85, 113, 141, and 169
measure: Absolute Subcutaneous Bioavailability (F%) of MEDI-551
timeFrame: Predose (Day 1) and Days 4, 8, 15, 29, 57, 85, 113, 141, and 169
measure: Absolute CD20 B-cell Count at Baseline
timeFrame: Baseline (Days -28 to -1)
measure: Time to 90 Percent (%) CD20 B-cell Depletion
timeFrame: Baseline (Days -28 to -1) to long-term follow-up (LTFU) (Up to 18 months after EDV or 24 Week treatment period)
measure: Duration of Suppression Greater Than or Equal to 90 % of CD20 B-cell Count
timeFrame: Baseline (Days -28 to -1) to LTFU (Up to 18 months after EDV or 24 Week treatment period)
measure: Maximum Change From Baseline in Absolute CD20 of Peripheral Blood B-cell Count to LTFU
timeFrame: Baseline (Days -28 to -1) to LTFU (Up to 18 months after EDV or 24 Week treatment period)
measure: Number of Participants Positive for Anti-Drug Antibodies to MEDI-551
timeFrame: Days 1, 29, 85 and 169
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Research Site
state: Arizona
city: Long Beach
country: United States
facility: Research Site
state: California
city: Sacramento
country: United States
facility: Research Site
state: California
city: Denver
country: United States
facility: Research Site
state: Colorado
city: Tampa
country: United States
facility: Research Site
state: Florida
city: Marlton
country: United States
facility: Research Site
state: New Jersey
city: Winston-Salem
country: United States
facility: Research Site
state: North Carolina
city: Cordova
country: United States
facility: Research Site
state: Tennessee
city: Houston
country: United States
facility: Research Site
state: Texas
city: Katowice
country: Poland
facility: Research Site
city: Szczecin
country: Poland
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Girona
country: Spain
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
city: Donetsk
country: Ukraine
facility: Research Site
city: Kyiv
country: Ukraine
facility: Research Site
Study officials:
affiliation: MedImmune LLC
name: Armando Flor
role: STUDY_DIRECTOR
References: