- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01585766
Safety and Tolerability Study of MEDI-551, a B-cell Depleting Agent, to Treat Relapsing Forms of Multiple Sclerosis
February 8, 2018 updated by: MedImmune LLC
A Phase 1 Randomized Study of MEDI-551 in Subjects With Relapsing Forms of Multiple Sclerosis
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).
Study Overview
Status
Completed
Conditions
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.
Study Type
Interventional
Enrollment (Actual)
56
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
-
Katowice, Poland
- Research Site
-
Szczecin, Poland
- Research Site
-
-
-
-
-
Barcelona, Spain
- Research Site
-
Girona, Spain
- Research Site
-
Sevilla, Spain
- Research Site
-
-
-
-
-
Donetsk, Ukraine
- Research Site
-
Kyiv, Ukraine
- Research Site
-
-
-
-
Arizona
-
Scottsdale, Arizona, United States
- Research Site
-
-
California
-
Long Beach, California, United States
- Research Site
-
Sacramento, California, United States
- Research Site
-
-
Colorado
-
Denver, Colorado, United States
- Research Site
-
-
Florida
-
Tampa, Florida, United States
- Research Site
-
-
New Jersey
-
Marlton, New Jersey, United States
- Research Site
-
-
North Carolina
-
Winston-Salem, North Carolina, United States
- Research Site
-
-
Tennessee
-
Cordova, Tennessee, United States
- Research Site
-
-
Texas
-
Houston, Texas, United States
- Research Site
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 65 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: MEDI-551 30 MG-IV
Participants received a fixed IV dose of 30 milligram (mg) MEDI-551 infused on Days 1 and 15.
|
Participants received a fixed IV dose of 30 milligram (mg) MEDI-551 infused on Days 1 and 15.
|
Experimental: MEDI-551 60 MG-SC
Participants received SC injection of 60 mg MEDI-551 on Day 1.
|
Participants received SC injection of 60 mg MEDI-551 on Day 1.
|
Experimental: MEDI-551 100 MG-IV
Participants received a fixed IV dose of 100 mg MEDI-551 infused on Days 1 and 15.
|
Participants received a fixed IV dose of 100 mg MEDI-551 infused on Days 1 and 15.
|
Experimental: MEDI-551 300 MG-SC
Participants received SC injection of 300 mg MEDI-551 on Day 1.
|
Participants received SC injection of 300 mg MEDI-551 on Day 1.
|
Experimental: MEDI-551 600 MG-IV
Participants received a fixed IV dose of 600 mg MEDI-551 infused on Days 1 and 15.
|
Participants received a fixed IV dose of 600 mg MEDI-551 infused on Days 1 and 15.
|
Placebo Comparator: PLACEBO-IV-SC
Participants received either a fixed IV dose of placebo matching with MEDI- 551 on Days 1 and 15 or SC injection on Day 1.
|
Participants received either a fixed IV dose of placebo matching with MEDI- 551 on Days 1 and 15 or SC injection on Day 1
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Time Frame: From study drug administration (Day 1) through the end of treatment period (Day 169)
|
An adverse event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug.
A TEAE were the events between administration of study drug (Day 1) and Day 169 that were absent before treatment or that worsened relative to pre-treatment state.
The AEs were summarized using Medical Dictionary for Regulatory Activities version 19.0
|
From study drug administration (Day 1) through the end of treatment period (Day 169)
|
Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs)
Time Frame: 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).
|
A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death, life-threatening, initial or prolonged inpatient hospitalization, persistent or significant disability or incapacity, congenital anomaly or birth defect in the offspring of a participant who received the study drug.
The TESAEs were the events between administration of study drug (Day 1) and long term follow up period (up to 18 months after early discontinuation visit or 24-week treatment period) that were absent before treatment or that worsened relative to pre-treatment state.
The AEs were summarized using Medical Dictionary for Regulatory Activities version 19.0
|
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).
|
Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs
Time Frame: From study drug administration (Day 1) through the end of treatment period (Day 169)
|
Any clinically significant change in laboratory evaluations were recorded as AEs.
The following parameters were analyzed for laboratory evaluations: haematology, serum chemistry, and urinalysis.
Number of participants with TEAEs related to laboratory evaluations were reported.
|
From study drug administration (Day 1) through the end of treatment period (Day 169)
|
Number of Participants With Vital Sign Abnormalities Reported as TEAEs
Time Frame: From study drug administration (Day 1) through the end of treatment period (Day 169)
|
Vital sign parameters included blood pressure, temperature, pulse rate, and respiratory rate.
The number of participants with TEAEs related to vital signs in participants were reported.
|
From study drug administration (Day 1) through the end of treatment period (Day 169)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Time to Reach Maximum Observed Serum Concentration (Tmax) of MEDI-551
Time Frame: 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
|
The time to reach the maximum observed serum concentration of MEDI-551.
|
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
|
Maximum Observed Serum Concentration (Cmax) of MEDI-551
Time Frame: 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
|
The maximum observed serum concentration (Cmax) of MEDI-551.
|
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
|
Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC 0-last) of MEDI-551
Time Frame: 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
|
The area under the concentration time curve from time 0 (dosing time) to the last measurable concentration (AUC 0-last) of MEDI-551.
|
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
|
Area Under the Plasma Concentration-time Curve From Zero to Infinity (AUC 0-infinity) of MEDI-551
Time Frame: 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
|
The area under the concentration-time curve from dosing extrapolated to infinity (AUC 0-infinity) of MEDI-551.
|
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
|
Dose Normalized Area Under the Plasma Concentration-time Curve From Zero to Infinity (AUC 0-infinity/D) of MEDI-551
Time Frame: 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
|
The AUC (0-infinity)/D is the area under concentration-time curve extrapolated to infinity post dose normalized by MEDI-551.
|
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
|
Clearance of MEDI-551
Time Frame: 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
|
Systemic clearance (CL) for MEDI-551 IV cohorts and apparent clearance (CL/F) for MEDI-551 SC cohorts were calculated
|
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
|
Terminal Elimination Half-life (t1/2) of MEDI-551
Time Frame: 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
|
The terminal elimination half-life (t1/2) was estimated based on the plasma concentrations of MEDI-551.
|
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
|
Absolute Subcutaneous Bioavailability (F%) of MEDI-551
Time Frame: Predose (Day 1) and Days 4, 8, 15, 29, 57, 85, 113, 141, and 169
|
Bioavailability (F%) is the fraction of the study drug absorbed through non-intravenous administration compared with the corresponding intravenous administration of the same drug.
|
Predose (Day 1) and Days 4, 8, 15, 29, 57, 85, 113, 141, and 169
|
Absolute CD20 B-cell Count at Baseline
Time Frame: Baseline (Days -28 to -1)
|
Baseline absolute CD20 count is measured as the average between screening and predose on Day 1.
|
Baseline (Days -28 to -1)
|
Time to 90 Percent (%) CD20 B-cell Depletion
Time Frame: Baseline (Days -28 to -1) to long-term follow-up (LTFU) (Up to 18 months after EDV or 24 Week treatment period)
|
Time in days of first observation where CD20 counts fall to or below 10 percent (%) of baseline.
|
Baseline (Days -28 to -1) to long-term follow-up (LTFU) (Up to 18 months after EDV or 24 Week treatment period)
|
Duration of Suppression Greater Than or Equal to 90 % of CD20 B-cell Count
Time Frame: Baseline (Days -28 to -1) to LTFU (Up to 18 months after EDV or 24 Week treatment period)
|
Time in days of last observation where CD20 counts remain at or below 10% of baseline.
Participants whose samples are available were analyzed for this outcome measure.
|
Baseline (Days -28 to -1) to LTFU (Up to 18 months after EDV or 24 Week treatment period)
|
Maximum Change From Baseline in Absolute CD20 of Peripheral Blood B-cell Count to LTFU
Time Frame: Baseline (Days -28 to -1) to LTFU (Up to 18 months after EDV or 24 Week treatment period)
|
The maximum degree of depletion (intensity) measured during the course of the study for each participant by subtracting 100 from the lowest observed percent of baseline value.
|
Baseline (Days -28 to -1) to LTFU (Up to 18 months after EDV or 24 Week treatment period)
|
Number of Participants Positive for Anti-Drug Antibodies to MEDI-551
Time Frame: Days 1, 29, 85 and 169
|
A participant was considered anti-drug antibody positive across the study if they had a positive reading at any time point during the study.
|
Days 1, 29, 85 and 169
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Director: Armando Flor, MedImmune LLC
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
April 24, 2012
Primary Completion (Actual)
January 2, 2015
Study Completion (Actual)
June 20, 2016
Study Registration Dates
First Submitted
April 9, 2012
First Submitted That Met QC Criteria
April 24, 2012
First Posted (Estimate)
April 26, 2012
Study Record Updates
Last Update Posted (Actual)
October 29, 2018
Last Update Submitted That Met QC Criteria
February 8, 2018
Last Verified
February 1, 2018
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- CD-IA-MEDI-551-1102
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Multiple Sclerosis, Relapsing Forms
-
BiogenWithdrawnRelapsing-Remitting Multiple Sclerosis | Relapsing Forms of Multiple Sclerosis
-
BiogenCompletedRelapsing Forms of Multiple SclerosisUnited States
-
Novartis PharmaceuticalsCompletedMultiple Sclerosis, Relapsing Forms of Multiple SclerosisSpain, Canada, France, Switzerland, Italy, Portugal, Denmark, Poland, Germany, United Kingdom
-
BiogenRecruitingRelapsing Forms of Multiple SclerosisSpain, United States, Italy, Switzerland, Germany, Bulgaria, Czechia, Poland, Puerto Rico, Romania
-
BiogenRecruitingRelapsing Forms of Multiple SclerosisChina, Japan
-
Novartis PharmaceuticalsCompletedRelapsing Forms of Multiple SclerosisGermany, South Africa, Italy, United States, Austria, Belgium, Czechia, Egypt, Hungary, Malaysia, Turkey, Spain, Australia, Canada, France, Israel, Netherlands, Switzerland, Greece, Korea, Republic of, Romania, Russian Federation, United... and more
-
BiogenCompletedRelapsing Forms of Multiple SclerosisUnited States
-
BiogenCompletedRelapsing Forms of Multiple SclerosisUnited States
-
Novartis PharmaceuticalsCompletedRelapsing Forms of Multiple SclerosisAustralia, United States
-
BiogenCompletedRelapsing Forms of Multiple SclerosisUnited States, Italy, Switzerland, Canada, Australia, Germany, Spain, France, Portugal, Netherlands, United Kingdom, Denmark, Austria, Ireland
Clinical Trials on MEDI-551 30 MG-IV
-
AmgenActive, not recruitingMyasthenia GravisUnited States, Argentina, Belarus, Brazil, Canada, China, Denmark, France, Germany, India, Italy, Japan, Korea, Republic of, Poland, Russian Federation, Spain, Taiwan, Turkey, Ukraine
-
Sidney Kimmel Comprehensive Cancer Center at Johns...TerminatedMultiple MyelomaUnited States
-
MedImmune LLCCompletedRelapsed/Refractory Aggressive B-cell LymphomasUnited States
-
MedImmune LLCCompletedSclerodermaUnited States, United Kingdom, Canada
-
AstraZenecaMedImmune LLCCompletedBlood Cancer | Advanced B Cell MalignanciesJapan
-
MedImmune LLCCompletedNeuromyelitis Optica and Neuromyelitis Optica Spectrum DisordersUnited States, Czechia, Thailand, Germany, Korea, Republic of, Israel, New Zealand, Spain, Taiwan, Japan, Turkey, Hungary, Bulgaria, Mexico, Russian Federation, Colombia, Peru, Poland, Estonia, South Africa, Canada, Australia, Hong... and more
-
MedImmune LLCCompletedDiffuse Large B-Cell LymphomaUnited States, France, Spain, Canada, Turkey, Israel, Germany, Russian Federation, Czechia, Hungary, Poland
-
Crucell Holland BVNational Institutes of Health (NIH); Division of Microbiology and Infectious...WithdrawnInfluenzaUnited States, Australia, Canada, France, Germany, Spain, Belgium, Bulgaria, Netherlands, Brazil, South Africa, Sweden
-
MedImmune LLCAstraZenecaTerminatedLupus Erythematosus, SystemicUnited States, Mexico, Peru, South Africa, Canada
-
Flame BiosciencesWithdrawnGastric Cancer | Solid Tumor | Pancreas Cancer