Trial Outcomes & Findings for An Open Label Study of the Effects of Eculizumab in Neuromyelitis Optica (NCT NCT00904826)

NCT ID: NCT00904826

Last Updated: 2013-11-04

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 14 participants
• Primary outcome timeframe: baseline, after 12 months of treatment
• Results posted on: 2013-11-04

Participant Flow

Between October 2009 and November 2010, subjects were directly recruited at the Mayo Clinics in Rochester, Minnesota and Scottsdale, Arizona, or identified through the Mayo Clinic study-specific repository or clinicoserological database.

Participant milestones

Measure	Eculizumab The patient will receive eculizumab at a dose of 600mg intravenously (an infusion given into the vein) each week for 4 weeks, then 900mg intravenously at the fifth week, then 900mg every 2 weeks for 48 weeks. Subjects will receive therapy for a total of 12 months.
Overall Study STARTED	14
Overall Study COMPLETED	14
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

An Open Label Study of the Effects of Eculizumab in Neuromyelitis Optica

Baseline characteristics by cohort

Measure	Eculizumab n=14 Participants The patient will receive eculizumab at a dose of 600mg intravenously (an infusion given into the vein) each week for 4 weeks, then 900mg intravenously at the fifth week, then 900mg every 2 weeks for 48 weeks. Subjects will receive therapy for a total of 12 months.
Age Continuous	41.1 years n=5 Participants
Sex: Female, Male Female	14 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Region of Enrollment United States	14 participants n=5 Participants
Ethnic origin African American	2 participants n=5 Participants
Ethnic origin Hispanic	3 participants n=5 Participants
Ethnic origin White	9 participants n=5 Participants
Diagnosis Neuromyelitis optica	8 participants n=5 Participants
Diagnosis Relapsing optic neuritis	2 participants n=5 Participants
Diagnosis Relapsing transverse myelitis	4 participants n=5 Participants
Coexisting autoimmune diseases Myasthenia gravis	2 participants n=5 Participants
Coexisting autoimmune diseases Idiopathic thrombocytopenic purpura	2 participants n=5 Participants
Coexisting autoimmune diseases Mixed connective tissue disease	2 participants n=5 Participants
Coexisting autoimmune diseases No coexisting autoimmune disease	10 participants n=5 Participants
Type of previous attacks at enrollment Optic neuritis	28 attacks n=5 Participants
Type of previous attacks at enrollment Transverse myelitis	52 attacks n=5 Participants
Type of previous attacks at enrollment Brainstem	1 attacks n=5 Participants
Type of previous attacks at enrollment Multifocal optic neuritis and transverse myelitis	3 attacks n=5 Participants
Type of previous attacks at enrollment Other multifocal	2 attacks n=5 Participants
Number of previous attacks per subject	5.5 attacks per subject n=5 Participants
Expanded Disability Status Scale (EDSS) Score	4.8 units on a scale n=5 Participants

PRIMARY outcome

Timeframe: baseline, after 12 months of treatment

Outcome measures

Measure	Eculizumab n=14 Participants The patient will receive eculizumab at a dose of 600mg intravenously (an infusion given into the vein) each week for 4 weeks, then 900mg intravenously at the fifth week, then 900mg every 2 weeks for 48 weeks. Subjects will receive therapy for a total of 12 months.
Median Number of Neuromyelitis Optica (NMO) Attacks Per Year Baseline	3 attacks per year Interval 2.0 to 4.0
Median Number of Neuromyelitis Optica (NMO) Attacks Per Year After 12 months of treatment	0 attacks per year Interval 0.0 to 1.0

SECONDARY outcome

Timeframe: 12 months

Outcome measures

Measure	Eculizumab n=14 Participants The patient will receive eculizumab at a dose of 600mg intravenously (an infusion given into the vein) each week for 4 weeks, then 900mg intravenously at the fifth week, then 900mg every 2 weeks for 48 weeks. Subjects will receive therapy for a total of 12 months.
Number Subjects Experiencing an NMO Attack in 12 Months of Eculizumab Treatment	2 participants

SECONDARY outcome

Timeframe: baseline, 12 months

The EDSS is an ordinal clinical rating scale ranging from 0 (normal neurologic examination) to 10 (death) in half-point increments.

Outcome measures

Measure	Eculizumab n=14 Participants The patient will receive eculizumab at a dose of 600mg intravenously (an infusion given into the vein) each week for 4 weeks, then 900mg intravenously at the fifth week, then 900mg every 2 weeks for 48 weeks. Subjects will receive therapy for a total of 12 months.
Change in Expanded Disability Status Scale (EDDS) Score	-0.7 units on a scale Interval -1.2 to -0.2

SECONDARY outcome

Timeframe: 12 months

Visual acuity was measured using the the Visual Acuity subscale of the Opticospinal Impairment Score (OSIS) for Exacerbations. This subscale ranges from 0 (normal) to 8 (no light perception).

Outcome measures

Measure	Eculizumab n=14 Participants The patient will receive eculizumab at a dose of 600mg intravenously (an infusion given into the vein) each week for 4 weeks, then 900mg intravenously at the fifth week, then 900mg every 2 weeks for 48 weeks. Subjects will receive therapy for a total of 12 months.
Number of Subjects With Change in Visual Acuity in at Least One Eye by at Least One Point	5 participants

SECONDARY outcome

Timeframe: 12 months

Ambulation was measured by the Hauser Ambulation Index, which ranges from 0 (asymptomatic; fully active) to 9 (restricted to wheelchair; unable to transfer self independently.)

Outcome measures

Measure	Eculizumab n=14 Participants The patient will receive eculizumab at a dose of 600mg intravenously (an infusion given into the vein) each week for 4 weeks, then 900mg intravenously at the fifth week, then 900mg every 2 weeks for 48 weeks. Subjects will receive therapy for a total of 12 months.
Number of Subjects With Change in Ambulation by at Least 1 Point	3 participants

SECONDARY outcome

Timeframe: 6 weeks, 3 months, 6 months, 9 months, 12 months

Population: Patient 13 was excluded from the 3 months measurement because she had temporarily discontinued treatment.

Outcome measures

Measure	Eculizumab n=14 Participants The patient will receive eculizumab at a dose of 600mg intravenously (an infusion given into the vein) each week for 4 weeks, then 900mg intravenously at the fifth week, then 900mg every 2 weeks for 48 weeks. Subjects will receive therapy for a total of 12 months.
Mean Serum Concentration of Eculizumab 6 weeks	206 micrograms/mL Standard Deviation 77
Mean Serum Concentration of Eculizumab 3 months	187 micrograms/mL Standard Deviation 91.2
Mean Serum Concentration of Eculizumab 9 months	230 micrograms/mL Standard Deviation 85.3
Mean Serum Concentration of Eculizumab 12 months	246 micrograms/mL Standard Deviation 102

SECONDARY outcome

Timeframe: baseline, 6 weeks, 3 months, 6 months, 9 months, 12 months

Population: Subject 13 was excluded at 3 months visit because she had temporarily discontinued treatment.

Percentage of hemolysis is a measure of complement activity. Less than 20% lysis is deemed to be complete complement inhibition.

Outcome measures

Measure	Eculizumab n=14 Participants The patient will receive eculizumab at a dose of 600mg intravenously (an infusion given into the vein) each week for 4 weeks, then 900mg intravenously at the fifth week, then 900mg every 2 weeks for 48 weeks. Subjects will receive therapy for a total of 12 months.
Percentage Hemolysis 12 months	0.9 percentage of hemolysis Standard Deviation 1.5
Percentage Hemolysis Baseline	88.5 percentage of hemolysis Standard Deviation 13.2
Percentage Hemolysis 6 weeks	0.4 percentage of hemolysis Standard Deviation 0.8
Percentage Hemolysis 3 months	0 percentage of hemolysis Standard Deviation 0
Percentage Hemolysis 6 months	0.2 percentage of hemolysis Standard Deviation 0.6
Percentage Hemolysis 9 months	0.4 percentage of hemolysis Standard Deviation 0.9

SECONDARY outcome

Timeframe: 3 months

Population: 12 subjects including subject 13 agreed to have CSF draw at the 3 month visit, but subject 13 was excluded because she had temporarily discontinued treatment.

Outcome measures

Measure	Eculizumab n=11 Participants The patient will receive eculizumab at a dose of 600mg intravenously (an infusion given into the vein) each week for 4 weeks, then 900mg intravenously at the fifth week, then 900mg every 2 weeks for 48 weeks. Subjects will receive therapy for a total of 12 months.
Mean Eculizumab Concentration in Cerebrospinal Fluid (CSF)	34.7 ng/mL Standard Deviation 18.7

SECONDARY outcome

Timeframe: baseline, 3 months

Population: At 3 months, C5 was undetectable in 6 subjects; patient 13 was excluded because she had temporarily discontinued treatment.

Outcome measures

Measure	Eculizumab n=14 Participants The patient will receive eculizumab at a dose of 600mg intravenously (an infusion given into the vein) each week for 4 weeks, then 900mg intravenously at the fifth week, then 900mg every 2 weeks for 48 weeks. Subjects will receive therapy for a total of 12 months.
Mean Complement Protein 5 (C5) Concentration in CSF Baseline	144 ng/mL Standard Deviation 75.5
Mean Complement Protein 5 (C5) Concentration in CSF 3 months	60.8 ng/mL Standard Deviation 23.3

Adverse Events

Eculizumab

Serious events: 1 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Measure	Eculizumab n=14 participants at risk The patient will receive eculizumab at a dose of 600mg intravenously (an infusion given into the vein) each week for 4 weeks, then 900mg intravenously at the fifth week, then 900mg every 2 weeks for 48 weeks. Subjects will receive therapy for a total of 12 months.
Infections and infestations Meningococcal infection	7.1% 1/14 • Number of events 1

Other adverse events

Measure	Eculizumab n=14 participants at risk The patient will receive eculizumab at a dose of 600mg intravenously (an infusion given into the vein) each week for 4 weeks, then 900mg intravenously at the fifth week, then 900mg every 2 weeks for 48 weeks. Subjects will receive therapy for a total of 12 months.
General disorders Headache	64.3% 9/14 • Number of events 23
Gastrointestinal disorders Nausea	42.9% 6/14 • Number of events 18
General disorders Dizziness	42.9% 6/14 • Number of events 13
Gastrointestinal disorders Diarrhea	42.9% 6/14 • Number of events 7
Respiratory, thoracic and mediastinal disorders Coughing	35.7% 5/14 • Number of events 6
General disorders Abdominal Pain	28.6% 4/14 • Number of events 5
Skin and subcutaneous tissue disorders Rash	21.4% 3/14 • Number of events 3
Musculoskeletal and connective tissue disorders Muscle cramps	14.3% 2/14 • Number of events 9
Infections and infestations Urinary tract infection	14.3% 2/14 • Number of events 6
General disorders Flu like symptoms	14.3% 2/14 • Number of events 3
Blood and lymphatic system disorders Swelling or ankle swelling	14.3% 2/14 • Number of events 2
General disorders Fatigue	14.3% 2/14 • Number of events 3
General disorders Nasal congestion or watery eyes	14.3% 2/14 • Number of events 3

Additional Information

Dr. Sean J. Pittock

Mayo Clinic

Phone: 507-284-4741

Email: pittock.sean@mayo.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place