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

Primary Purpose

Multiple Sclerosis, Relapsing Forms

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

MEDI-551 30 MG-IV

MEDI-551 60 MG-SC

PLACEBO-IV-SC

MEDI-551 100 MG-IV

MEDI-551 300 MG-SC

MEDI-551 600 MG-IV

About this trial

This is an interventional treatment trial for Multiple Sclerosis, Relapsing Forms focused on measuring MAb, B cell, depletion, RMS

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Placebo Comparator

Arm Label

MEDI-551 30 MG-IV

MEDI-551 60 MG-SC

MEDI-551 100 MG-IV

MEDI-551 300 MG-SC

MEDI-551 600 MG-IV

PLACEBO-IV-SC

Arm Description

Participants received a fixed IV dose of 30 milligram (mg) MEDI-551 infused on Days 1 and 15.

Participants received SC injection of 60 mg MEDI-551 on Day 1.

Participants received a fixed IV dose of 100 mg MEDI-551 infused on Days 1 and 15.

Participants received SC injection of 300 mg MEDI-551 on Day 1.

Participants received a fixed IV dose of 600 mg MEDI-551 infused on Days 1 and 15.

Participants received either a fixed IV dose of placebo matching with MEDI- 551 on Days 1 and 15 or SC injection on Day 1.

Outcomes

Primary Outcome Measures

Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

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

Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs)

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

Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs

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.

Number of Participants With Vital Sign Abnormalities Reported as TEAEs

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

Time to Reach Maximum Observed Serum Concentration (Tmax) of MEDI-551

The time to reach the maximum observed serum concentration of MEDI-551.

Maximum Observed Serum Concentration (Cmax) of MEDI-551

The maximum observed serum concentration (Cmax) of MEDI-551.

Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC 0-last) of MEDI-551

The area under the concentration time curve from time 0 (dosing time) to the last measurable concentration (AUC 0-last) of MEDI-551.

Area Under the Plasma Concentration-time Curve From Zero to Infinity (AUC 0-infinity) of MEDI-551

The area under the concentration-time curve from dosing extrapolated to infinity (AUC 0-infinity) of MEDI-551.

Dose Normalized Area Under the Plasma Concentration-time Curve From Zero to Infinity (AUC 0-infinity/D) of MEDI-551

The AUC (0-infinity)/D is the area under concentration-time curve extrapolated to infinity post dose normalized by MEDI-551.

Clearance of MEDI-551

Systemic clearance (CL) for MEDI-551 IV cohorts and apparent clearance (CL/F) for MEDI-551 SC cohorts were calculated

Terminal Elimination Half-life (t1/2) of MEDI-551

The terminal elimination half-life (t1/2) was estimated based on the plasma concentrations of MEDI-551.

Absolute Subcutaneous Bioavailability (F%) of MEDI-551

Bioavailability (F%) is the fraction of the study drug absorbed through non-intravenous administration compared with the corresponding intravenous administration of the same drug.

Absolute CD20 B-cell Count at Baseline

Baseline absolute CD20 count is measured as the average between screening and predose on Day 1.

Time to 90 Percent (%) CD20 B-cell Depletion

Time in days of first observation where CD20 counts fall to or below 10 percent (%) of baseline.

Duration of Suppression Greater Than or Equal to 90 % of CD20 B-cell Count

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.

Maximum Change From Baseline in Absolute CD20 of Peripheral Blood B-cell Count to LTFU

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.

Number of Participants Positive for Anti-Drug Antibodies to MEDI-551

A participant was considered anti-drug antibody positive across the study if they had a positive reading at any time point during the study.

Full Information

NCT ID

NCT01585766

First Posted

April 9, 2012

Last Updated

February 8, 2018

Sponsor

MedImmune LLC

1. Study Identification

Unique Protocol Identification Number

NCT01585766

Brief Title

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

2. Study Status

Record Verification Date

February 2018

Overall Recruitment Status

Completed

Study Start Date

April 24, 2012 (Actual)

Primary Completion Date

January 2, 2015 (Actual)

Study Completion Date

June 20, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

MedImmune LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Multiple Sclerosis, Relapsing Forms

Keywords

MAb, B cell, depletion, RMS

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

56 (Actual)

8. Arms, Groups, and Interventions

Arm Title

MEDI-551 30 MG-IV

Arm Type

Experimental

Arm Description

Participants received a fixed IV dose of 30 milligram (mg) MEDI-551 infused on Days 1 and 15.

Arm Title

MEDI-551 60 MG-SC

Arm Type

Experimental

Arm Description

Participants received SC injection of 60 mg MEDI-551 on Day 1.

Arm Title

MEDI-551 100 MG-IV

Arm Type

Experimental

Arm Description

Participants received a fixed IV dose of 100 mg MEDI-551 infused on Days 1 and 15.

Arm Title

MEDI-551 300 MG-SC

Arm Type

Experimental

Arm Description

Participants received SC injection of 300 mg MEDI-551 on Day 1.

Arm Title

MEDI-551 600 MG-IV

Arm Type

Experimental

Arm Description

Participants received a fixed IV dose of 600 mg MEDI-551 infused on Days 1 and 15.

Arm Title

PLACEBO-IV-SC

Arm Type

Placebo Comparator

Arm Description

Participants received either a fixed IV dose of placebo matching with MEDI- 551 on Days 1 and 15 or SC injection on Day 1.

Intervention Type

Drug

Intervention Name(s)

MEDI-551 30 MG-IV

Intervention Description

Participants received a fixed IV dose of 30 milligram (mg) MEDI-551 infused on Days 1 and 15.

Intervention Type

Drug

Intervention Name(s)

MEDI-551 60 MG-SC

Intervention Description

Participants received SC injection of 60 mg MEDI-551 on Day 1.

Intervention Type

Drug

Intervention Name(s)

PLACEBO-IV-SC

Intervention Description

Participants received either a fixed IV dose of placebo matching with MEDI- 551 on Days 1 and 15 or SC injection on Day 1

Intervention Type

Drug

Intervention Name(s)

MEDI-551 100 MG-IV

Intervention Description

Participants received a fixed IV dose of 100 mg MEDI-551 infused on Days 1 and 15.

Intervention Type

Drug

Intervention Name(s)

MEDI-551 300 MG-SC

Intervention Description

Participants received SC injection of 300 mg MEDI-551 on Day 1.

Intervention Type

Drug

Intervention Name(s)

MEDI-551 600 MG-IV

Intervention Description

Participants received a fixed IV dose of 600 mg MEDI-551 infused on Days 1 and 15.

Primary Outcome Measure Information:

Title

Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

Description

Time Frame

From study drug administration (Day 1) through the end of treatment period (Day 169)

Title

Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs)

Description

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).

Title

Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs

Description

Time Frame

From study drug administration (Day 1) through the end of treatment period (Day 169)

Title

Number of Participants With Vital Sign Abnormalities Reported as TEAEs

Description

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.

Time Frame

From study drug administration (Day 1) through the end of treatment period (Day 169)

Secondary Outcome Measure Information:

Title

Time to Reach Maximum Observed Serum Concentration (Tmax) of MEDI-551

Description

The time to reach the maximum observed serum concentration of MEDI-551.

Time Frame