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Safety and Tolerability Study of MEDI-551, a B-cell Depleting Agent, to Treat Relapsing Forms of Multiple Sclerosis

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ClinicalTrials.gov Identifier: NCT01585766
Recruitment Status : Completed
First Posted : April 26, 2012
Results First Posted : October 29, 2018
Last Update Posted : October 29, 2018
Sponsor:
Information provided by (Responsible Party):
MedImmune LLC

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).

Condition or disease Intervention/treatment Phase
Multiple Sclerosis, Relapsing Forms Drug: MEDI-551 30 MG-IV Drug: MEDI-551 60 MG-SC Drug: PLACEBO-IV-SC Drug: MEDI-551 100 MG-IV Drug: MEDI-551 300 MG-SC Drug: MEDI-551 600 MG-IV Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 56 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 1 Randomized Study of MEDI-551 in Subjects With Relapsing Forms of Multiple Sclerosis
Actual Study Start Date : April 24, 2012
Actual Primary Completion Date : January 2, 2015
Actual Study Completion Date : June 20, 2016

Resource links provided by the National Library of Medicine


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.
Drug: MEDI-551 30 MG-IV
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.
Drug: MEDI-551 60 MG-SC
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.
Drug: MEDI-551 100 MG-IV
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.
Drug: MEDI-551 300 MG-SC
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.
Drug: MEDI-551 600 MG-IV
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.
Drug: 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




Primary Outcome Measures :
  1. 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

  2. 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

  3. 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.

  4. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01585766


Locations
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United States, Arizona
Research Site
Scottsdale, Arizona, United States
United States, California
Research Site
Long Beach, California, United States
Research Site
Sacramento, California, United States
United States, Colorado
Research Site
Denver, Colorado, United States
United States, Florida
Research Site
Tampa, Florida, United States
United States, New Jersey
Research Site
Marlton, New Jersey, United States
United States, North Carolina
Research Site
Winston-Salem, North Carolina, United States
United States, Tennessee
Research Site
Cordova, Tennessee, United States
United States, Texas
Research Site
Houston, Texas, United States
Poland
Research Site
Katowice, Poland
Research Site
Szczecin, Poland
Spain
Research Site
Barcelona, Spain
Research Site
Girona, Spain
Research Site
Sevilla, Spain
Ukraine
Research Site
Donetsk, Ukraine
Research Site
Kyiv, Ukraine
Sponsors and Collaborators
MedImmune LLC
Investigators
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Study Director: Armando Flor MedImmune LLC
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Responsible Party: MedImmune LLC
ClinicalTrials.gov Identifier: NCT01585766    
Other Study ID Numbers: CD-IA-MEDI-551-1102
First Posted: April 26, 2012    Key Record Dates
Results First Posted: October 29, 2018
Last Update Posted: October 29, 2018
Last Verified: February 2018

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by MedImmune LLC:
MAb, B cell, depletion, RMS
Additional relevant MeSH terms:
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Multiple Sclerosis
Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases