Atacicept in Subjects With Optic Neuritis

A Two-arm, Randomized, Double-blind, Placebo-controlled, Multicenter Phase II Study to Evaluate Safety and Tolerability and to Explore the Neuroprotective Effect of Atacicept as Assessed by Optical Coherence Tomography (OCT) in Subjects With Optic Neuritis (ON) as Clinically Isolated Syndrome (CIS) Over a 36-week Treatment Course

This study was intended to evaluate the efficacy, safety and tolerability of atacicept compared to placebo and to explore the neuroprotective effect of atacicept as assessed by OCT in subjects with ON as CIS. The study was randomized. Study medication was administered via subcutaneous (under the skin) injections.

Study Overview

• Status: Terminated
• Conditions: Optic Neuritis
• Intervention / Treatment: Drug: Placebo matched to atacicept; Drug: Atacicept

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Parkville, Victoria, Australia
      • Research Site
• Belgium
  • Bruxelles, Belgium
    • Research Site
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada
      • Research Site
  • Ontario
    • Ottawa, Ontario, Canada
      • Research Site
  • Quebec
    • Montreal, Quebec, Canada
      • Research Site
• Czech Republic
  • Hradec Kralove, Czech Republic
    • Research Site
  • Olomouc, Czech Republic
    • Research Site
• France
  • Paris, France
    • Research Site
• Germany
  • Freiburg, Germany
    • Research Site
  • Munich, Germany
    • Research Site
  • Tübingen, Germany
    • Research Site
  • Würzburg, Germany
    • Research Site
• Lebanon
  • Beyrouth, Lebanon
    • Research Site
  • Dbayeh, Lebanon
    • Research Site
• Spain
  • Barcelona, Spain
    • Research Site
  • Sevilla, Spain
    • Research Site
  • Valencia, Spain
    • Research Site
• Switzerland
  • Lausanne, Switzerland
    • Research Site
• United Kingdom
  • London, United Kingdom
    • Research Site
  • Sheffield, United Kingdom
    • Research Site
• United States
  • Alabama
    • Birmingham, Alabama, United States
      • Research Site
  • Colorado
    • Aurora, Colorado, United States
      • Research Site
  • Connecticut
    • Fairfield, Connecticut, United States
      • Research Site
  • Florida
    • Jacksonville, Florida, United States
      • Research Site
  • Michigan
    • East Lansing, Michigan, United States
      • Research Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States
      • Research Site
  • Texas
    • Houston, Texas, United States
      • Research Site
  • Vermont
    • Burlington, Vermont, United States
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of unilateral symptomatic optic neuritis as first clinical manifestation within 28 days between onset of symptoms and study Day 1
• Other protocol defined inclusion criteria could apply

Exclusion Criteria:

• Pre treatment with immunosuppressants and immunomodulating drugs
• Relevant cardiac, hepatic and renal diseases
• Clinical significant abnormalities in blood cell counts and immunoglobulin levels
• Clinical significant acute or chronic infections
• Other protocol defined exclusion criteria could apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo matched to atacicept; Placebo matched to atacicept will be administered subcutaneously twice a week for initial 4 weeks, followed by once a week for subsequent 32 weeks.
Experimental: Atacicept	Drug: Atacicept; Atacicept will be administered subcutaneously at a dose of 150 milligram (mg) twice a week for initial 4 weeks as loading dose, followed by 150 mg once a week for subsequent 32 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Retinal Nerve Fiber Layer (RNFL) Thickness in the Affected Eye at Last Observed Value (LOV)	The RNFL thickness was measured for 12 sectors (every 30 degrees) per eye in triplicate by optical coherence tomography (OCT) measurements and were then averaged over 12 sectors. The change in RNFL thickness at LOV visit was calculated as RNFL thickness at LOV minus RNFL thickness at baseline.	Baseline, LOV (Week 48)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in Retinal Nerve Fibre Layer (RNFL) Thickness Between the Affected Eye and Fellow Eye	The RNFL thickness was measured for 12 sectors (every 30 degrees) per eye in triplicate by optical coherence tomography (OCT) measurements and was then averaged over 12 sectors. Difference was calculated as RNFL thickness in affected eye minus RNFL thickness in fellow eye.	Weeks 12, 24 and 36
Change From Baseline in Retinal Nerve Fiber Layer (RNFL) Thickness in the Affected Eye at Weeks 12 and 24	The RNFL thickness was measured for 12 sectors (every 30 degrees) per eye in triplicate by OCT measurements and was then averaged over 12 sectors. The change in RNFL thickness at Weeks 12 and 24 was calculated as RNFL thickness at Weeks 12 and 24 minus RNFL thickness at baseline, respectively.	Baseline, Weeks 12 and 24
Change From Baseline in Macular Thickness at 3 Millimeter (mm) Around Fovea in the Affected Eye at Weeks 12, 24 and 36	The change in macular thickness at 3 mm around fovea in the affected eye at Weeks 12, 24 and 36 was calculated as macular thickness at 3 mm in the affected eye at Weeks 12, 24 and 36 minus macular thickness at 3 mm in the affected eye at baseline, respectively.	Baseline, Weeks 12, 24 and 36
Change From Baseline in Macular Thickness at 6 Millimeter (mm) Around Fovea in the Affected Eye at Weeks 12, 24 and 36	The change in macular thickness at 6 mm around fovea in the affected eye at Weeks 12, 24 and 36 was calculated as macular thickness at 6 mm in the affected eye at Weeks 12, 24 and 36 minus macular thickness at 6 mm in the affected eye at baseline, respectively.	Baseline, Weeks 12, 24 and 36
Change From Baseline in Macular Volume in the Affected Eye at Weeks 12, 24 and 36	The change in macular volume in the affected eye at Weeks 12, 24 and 36 was calculated as macular volume in the affected eye at Weeks 12, 24 and 36 minus macular volume in the affected eye at baseline, respectively.	Baseline, Weeks 12, 24 and 36
Low-Contrast Letter Acuity: Total Number of Letters Correctly Identified	Low-contrast letter acuity was measured by using the Sloan Charts at 1.25 fraction (%) and 2.5%. Sloan letters are a set of optotypes used to test visual acuity. Total number of letters correctly identified in the affected and fellow eye were reported. The possible Sloan Chart range is 0 to 70. More the number of letters identified, better is the visual acuity.	Weeks 12, 24 and 36
Contrast Sensitivity: Total Number of Letters Correctly Identified	Contrast Sensitivity was measured using the Pelli-Robson Charts. Pelli-Robson chart is used for clinical measurement of contrast sensitivity and determines the contrast required to read large letters of a fixed size. Total number of letters correctly identified in the affected and fellow eye were reported. The total possible range is 0 to 48. More the number of letters identified, better is the contrast sensitivity.	Weeks 12, 24 and 36
Contrast Sensitivity: Score Line	Contrast sensitivity was measured using the Pelli-Robson charts with letters arranged in groups of 3. Pelli-Robson chart is used for clinical measurement of contrast sensitivity and determines the contrast required to read large letters of a fixed size. The possible score line range is 0 (visual disability) to 16 (normal contrast sensitivity).	Weeks 12, 24 and 36
Percentage of Participants Converting to Clinically Definite Multiple Sclerosis (CDMS) Second Clinical Attack	Conversion to CDMS was defined as experiencing a second clinical attack meeting all of the following criteria: (a) Neurological abnormality, either newly appearing or re-appearing, with abnormality specified by both (i) Neurological abnormality separated by at least 30 days from onset of a preceding clinical event, and (ii) Neurological abnormality lasting for at least 24 hours; (b) Absence of fever or known infection (fever with temperature [axillary, orally or intraauricularly] greater than 37.5 degree Celsius/99.5 degree Fahrenheit); (c) Objective neurological impairment, correlating with the participant's reported symptoms, defined as either (i) Increase in at least 1 of the functional systems of the Expanded Disability Status Score (EDSS), or (ii) Increase of the total EDSS score. EDSS assesses disability in 8 functional systems and total score ranges from 0 (normal) to 10 (death due to MS). Percentage of participants converting to CDMS (second clinical attack) was reported.	From baseline (Study Day 1) up to Week 36

Collaborators and Investigators

• Sponsor: EMD Serono
• Collaborators: Merck KGaA, Darmstadt, Germany
• Investigators: Study Director: Medical Responsible, EMD Serono, an affiliate of MerckKGaA, Darmstadt, Germany

Study record dates

Study Major Dates

• Study Start: June 1, 2008
• Primary Completion (Actual): September 1, 2009
• Study Completion (Actual): January 1, 2011

Study Registration Dates

• First Submitted: February 15, 2008
• First Submitted That Met QC Criteria: February 25, 2008
• First Posted (Estimate): February 27, 2008

Study Record Updates

• Last Update Posted (Estimate): February 17, 2016
• Last Update Submitted That Met QC Criteria: January 19, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Keywords: atacicept; neuritis
• Additional Relevant MeSH Terms: Nervous System Diseases; Eye Diseases; Neuromuscular Diseases; Peripheral Nervous System Diseases; Optic Nerve Diseases; Cranial Nerve Diseases; Neuritis; Optic Neuritis
• Other Study ID Numbers: 28156