Optic Neuritis
Conditions
Keywords
atacicept, neuritis
Brief summary
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.
Interventions
DRUGAtacicept
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.
Placebo matched to atacicept will be administered subcutaneously twice a week for initial 4 weeks, followed by once a week for subsequent 32 weeks.
Sponsors
Merck KGaA, Darmstadt, Germany
EMD Serono
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Retinal Nerve Fiber Layer (RNFL) Thickness in the Affected Eye at Last Observed Value (LOV) | Baseline, LOV (Week 48) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Difference in Retinal Nerve Fibre Layer (RNFL) Thickness Between the Affected Eye and Fellow Eye | Weeks 12, 24 and 36 | 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. |
| Change From Baseline in Retinal Nerve Fiber Layer (RNFL) Thickness in the Affected Eye at Weeks 12 and 24 | Baseline, 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. |
| Change From Baseline in Macular Thickness at 3 Millimeter (mm) Around Fovea in the Affected Eye at Weeks 12, 24 and 36 | Baseline, 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. |
| Change From Baseline in Macular Thickness at 6 Millimeter (mm) Around Fovea in the Affected Eye at Weeks 12, 24 and 36 | Baseline, 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. |
| Change From Baseline in Macular Volume in the Affected Eye at Weeks 12, 24 and 36 | Baseline, 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. |
| Low-Contrast Letter Acuity: Total Number of Letters Correctly Identified | Weeks 12, 24 and 36 | 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. |
| Contrast Sensitivity: Total Number of Letters Correctly Identified | Weeks 12, 24 and 36 | 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. |
| Contrast Sensitivity: Score Line | Weeks 12, 24 and 36 | 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). |
| Percentage of Participants Converting to Clinically Definite Multiple Sclerosis (CDMS) Second Clinical Attack | From baseline (Study Day 1) up to Week 36 | 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. |
Countries
Australia, Belgium, Canada, Czechia, France, Germany, Lebanon, Spain, Switzerland, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo: Double-blind Period Placebo matched to atacicept was administered subcutaneously twice a week for initial 4 weeks, followed by once a week for subsequent 32 weeks. | 17 |
| Atacicept: Double-blind Period Atacicept was 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. | 17 |
| Total | 34 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Double-blind Period | Early Termination Initiated by Sponsor | 13 | 12 | 0 | 0 |
| Double-blind Period | Withdrew Prematurely | 1 | 1 | 0 | 0 |
| Safety Follow-up (SFU) Period | Lost to Follow-up | 0 | 0 | 1 | 2 |
| Safety Follow-up (SFU) Period | Other | 0 | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Placebo: Double-blind Period | Atacicept: Double-blind Period | Total |
|---|---|---|---|
| Age, Continuous | 32.3 years STANDARD_DEVIATION 7.1 | 30.6 years STANDARD_DEVIATION 10.2 | 31.4 years STANDARD_DEVIATION 8.7 |
| Sex: Female, Male Female | 14 Participants | 13 Participants | 27 Participants |
| Sex: Female, Male Male | 3 Participants | 4 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 14 / 17 | 16 / 17 | 6 / 13 | 10 / 14 |
| serious Total, serious adverse events | 0 / 17 | 0 / 17 | 1 / 13 | 2 / 14 |
Outcome results
Primary
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.
Time frame: Baseline, LOV (Week 48)
Population: ITT population included all randomized participants. Here, n signifies those participants who were evaluable for the specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo: Double-blind Period | Change From Baseline in Retinal Nerve Fiber Layer (RNFL) Thickness in the Affected Eye at Last Observed Value (LOV) | Baseline (n = 17, 17) | 103.893 micrometer | Standard Deviation 17.271 |
| Placebo: Double-blind Period | Change From Baseline in Retinal Nerve Fiber Layer (RNFL) Thickness in the Affected Eye at Last Observed Value (LOV) | Change at LOV (n = 16, 15) | -17.317 micrometer | Standard Deviation 15.158 |
| Atacicept: Double-blind Period | Change From Baseline in Retinal Nerve Fiber Layer (RNFL) Thickness in the Affected Eye at Last Observed Value (LOV) | Baseline (n = 17, 17) | 104.170 micrometer | Standard Deviation 8.832 |
| Atacicept: Double-blind Period | Change From Baseline in Retinal Nerve Fiber Layer (RNFL) Thickness in the Affected Eye at Last Observed Value (LOV) | Change at LOV (n = 16, 15) | -8.636 micrometer | Standard Deviation 10.056 |
Secondary
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.
Time frame: Baseline, Weeks 12, 24 and 36
Population: ITT population included all randomized participants. Here, n signifies those participants who were evaluable for the specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo: Double-blind Period | Change From Baseline in Macular Thickness at 3 Millimeter (mm) Around Fovea in the Affected Eye at Weeks 12, 24 and 36 | Baseline (n = 17, 17) | 1054.4 micrometer | Standard Deviation 76.5 |
| Placebo: Double-blind Period | Change From Baseline in Macular Thickness at 3 Millimeter (mm) Around Fovea in the Affected Eye at Weeks 12, 24 and 36 | Change at Week 24 (n = 4, 5) | -72.5 micrometer | Standard Deviation 47 |
| Placebo: Double-blind Period | Change From Baseline in Macular Thickness at 3 Millimeter (mm) Around Fovea in the Affected Eye at Weeks 12, 24 and 36 | Change at Week 12 (n = 13, 13) | -29.3 micrometer | Standard Deviation 34.4 |
| Placebo: Double-blind Period | Change From Baseline in Macular Thickness at 3 Millimeter (mm) Around Fovea in the Affected Eye at Weeks 12, 24 and 36 | Change at Week 36 (n = 3, 4) | -32.7 micrometer | Standard Deviation 30.7 |
| Atacicept: Double-blind Period | Change From Baseline in Macular Thickness at 3 Millimeter (mm) Around Fovea in the Affected Eye at Weeks 12, 24 and 36 | Change at Week 12 (n = 13, 13) | -34.0 micrometer | Standard Deviation 21.8 |
| Atacicept: Double-blind Period | Change From Baseline in Macular Thickness at 3 Millimeter (mm) Around Fovea in the Affected Eye at Weeks 12, 24 and 36 | Baseline (n = 17, 17) | 1070.6 micrometer | Standard Deviation 72.7 |
| Atacicept: Double-blind Period | Change From Baseline in Macular Thickness at 3 Millimeter (mm) Around Fovea in the Affected Eye at Weeks 12, 24 and 36 | Change at Week 36 (n = 3, 4) | -40.0 micrometer | Standard Deviation 51.3 |
| Atacicept: Double-blind Period | Change From Baseline in Macular Thickness at 3 Millimeter (mm) Around Fovea in the Affected Eye at Weeks 12, 24 and 36 | Change at Week 24 (n = 4, 5) | -50.4 micrometer | Standard Deviation 47.7 |
Secondary
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.
Time frame: Baseline, Weeks 12, 24 and 36
Population: ITT population included all randomized participants. Here, n signifies those participants who were evaluable for the specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo: Double-blind Period | Change From Baseline in Macular Thickness at 6 Millimeter (mm) Around Fovea in the Affected Eye at Weeks 12, 24 and 36 | Baseline (n = 17, 17) | 954.4 micrometer | Standard Deviation 57.4 |
| Placebo: Double-blind Period | Change From Baseline in Macular Thickness at 6 Millimeter (mm) Around Fovea in the Affected Eye at Weeks 12, 24 and 36 | Change at Week 12 (n = 13, 13) | -36.1 micrometer | Standard Deviation 28.4 |
| Placebo: Double-blind Period | Change From Baseline in Macular Thickness at 6 Millimeter (mm) Around Fovea in the Affected Eye at Weeks 12, 24 and 36 | Change at Week 24 (n = 4, 5) | -63.8 micrometer | Standard Deviation 32.7 |
| Placebo: Double-blind Period | Change From Baseline in Macular Thickness at 6 Millimeter (mm) Around Fovea in the Affected Eye at Weeks 12, 24 and 36 | Change at Week 36 (n = 3, 4) | -33.3 micrometer | Standard Deviation 33.7 |
| Atacicept: Double-blind Period | Change From Baseline in Macular Thickness at 6 Millimeter (mm) Around Fovea in the Affected Eye at Weeks 12, 24 and 36 | Change at Week 36 (n = 3, 4) | -34.8 micrometer | Standard Deviation 46 |
| Atacicept: Double-blind Period | Change From Baseline in Macular Thickness at 6 Millimeter (mm) Around Fovea in the Affected Eye at Weeks 12, 24 and 36 | Baseline (n = 17, 17) | 947.5 micrometer | Standard Deviation 61.3 |
| Atacicept: Double-blind Period | Change From Baseline in Macular Thickness at 6 Millimeter (mm) Around Fovea in the Affected Eye at Weeks 12, 24 and 36 | Change at Week 24 (n = 4, 5) | -46.2 micrometer | Standard Deviation 36.5 |
| Atacicept: Double-blind Period | Change From Baseline in Macular Thickness at 6 Millimeter (mm) Around Fovea in the Affected Eye at Weeks 12, 24 and 36 | Change at Week 12 (n = 13, 13) | -32.8 micrometer | Standard Deviation 25.2 |
Secondary
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.
Time frame: Baseline, Weeks 12, 24 and 36
Population: ITT population included all randomized participants. Here, n signifies those participants who were evaluable for the specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo: Double-blind Period | Change From Baseline in Macular Volume in the Affected Eye at Weeks 12, 24 and 36 | Change at Week 36 (n = 3, 4) | -0.2353 cubic micrometer | Standard Deviation 0.2253 |
| Placebo: Double-blind Period | Change From Baseline in Macular Volume in the Affected Eye at Weeks 12, 24 and 36 | Change at Week 12 (n = 13, 13) | -0.2389 cubic micrometer | Standard Deviation 0.1991 |
| Placebo: Double-blind Period | Change From Baseline in Macular Volume in the Affected Eye at Weeks 12, 24 and 36 | Change at Week 24 (n = 4, 5) | -0.4630 cubic micrometer | Standard Deviation 0.2466 |
| Placebo: Double-blind Period | Change From Baseline in Macular Volume in the Affected Eye at Weeks 12, 24 and 36 | Baseline (n = 17, 17) | 6.8865 cubic micrometer | Standard Deviation 0.4199 |
| Atacicept: Double-blind Period | Change From Baseline in Macular Volume in the Affected Eye at Weeks 12, 24 and 36 | Baseline (n = 17, 17) | 6.8794 cubic micrometer | Standard Deviation 0.4372 |
| Atacicept: Double-blind Period | Change From Baseline in Macular Volume in the Affected Eye at Weeks 12, 24 and 36 | Change at Week 36 (n = 3, 4) | -0.2533 cubic micrometer | Standard Deviation 0.3205 |
| Atacicept: Double-blind Period | Change From Baseline in Macular Volume in the Affected Eye at Weeks 12, 24 and 36 | Change at Week 24 (n = 4, 5) | -0.3292 cubic micrometer | Standard Deviation 0.2674 |
| Atacicept: Double-blind Period | Change From Baseline in Macular Volume in the Affected Eye at Weeks 12, 24 and 36 | Change at Week 12 (n = 13, 13) | -0.2301 cubic micrometer | Standard Deviation 0.1612 |
Secondary
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.
Time frame: Baseline, Weeks 12 and 24
Population: ITT population included all randomized participants. Here, N (number of participants analyzed) signifies those participants who were evaluable for this outcome measure and n signifies those participants who were evaluable for the specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo: Double-blind Period | Change From Baseline in Retinal Nerve Fiber Layer (RNFL) Thickness in the Affected Eye at Weeks 12 and 24 | Baseline (n=17, 17) | 103.893 micrometer | Standard Deviation 17.271 |
| Placebo: Double-blind Period | Change From Baseline in Retinal Nerve Fiber Layer (RNFL) Thickness in the Affected Eye at Weeks 12 and 24 | Change at Week 12 (n = 13, 13) | -17.036 micrometer | Standard Deviation 13.919 |
| Placebo: Double-blind Period | Change From Baseline in Retinal Nerve Fiber Layer (RNFL) Thickness in the Affected Eye at Weeks 12 and 24 | Change at Week 24 (n = 4, 5) | -17.815 micrometer | Standard Deviation 16.505 |
| Atacicept: Double-blind Period | Change From Baseline in Retinal Nerve Fiber Layer (RNFL) Thickness in the Affected Eye at Weeks 12 and 24 | Baseline (n=17, 17) | 104.170 micrometer | Standard Deviation 8.832 |
| Atacicept: Double-blind Period | Change From Baseline in Retinal Nerve Fiber Layer (RNFL) Thickness in the Affected Eye at Weeks 12 and 24 | Change at Week 12 (n = 13, 13) | -9.356 micrometer | Standard Deviation 9.532 |
| Atacicept: Double-blind Period | Change From Baseline in Retinal Nerve Fiber Layer (RNFL) Thickness in the Affected Eye at Weeks 12 and 24 | Change at Week 24 (n = 4, 5) | -11.234 micrometer | Standard Deviation 14.23 |
Secondary
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).
Time frame: Weeks 12, 24 and 36
Population: ITT population included all randomized participants. Here, N (number of participants analyzed) signifies those participants who were evaluable for this outcome measure and n signifies those participants who were evaluable for the specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo: Double-blind Period | Contrast Sensitivity: Score Line | Affected eye: Week 12 (n = 15, 14) | 12.1 units on a scale | Standard Deviation 1.5 |
| Placebo: Double-blind Period | Contrast Sensitivity: Score Line | Affected eye: Week 24 (n = 5, 5) | 11.4 units on a scale | Standard Deviation 2.6 |
| Placebo: Double-blind Period | Contrast Sensitivity: Score Line | Affected eye: Week 36 (n = 3, 3) | 12.3 units on a scale | Standard Deviation 2.1 |
| Placebo: Double-blind Period | Contrast Sensitivity: Score Line | Fellow eye: Week 12 (n = 15, 14) | 12.9 units on a scale | Standard Deviation 1.5 |
| Placebo: Double-blind Period | Contrast Sensitivity: Score Line | Fellow eye: Week 24 (n = 5, 5) | 11.8 units on a scale | Standard Deviation 3.3 |
| Placebo: Double-blind Period | Contrast Sensitivity: Score Line | Fellow eye: Week 36 (n = 3, 3) | 13.3 units on a scale | Standard Deviation 1.2 |
| Atacicept: Double-blind Period | Contrast Sensitivity: Score Line | Fellow eye: Week 24 (n = 5, 5) | 12.4 units on a scale | Standard Deviation 0.5 |
| Atacicept: Double-blind Period | Contrast Sensitivity: Score Line | Affected eye: Week 12 (n = 15, 14) | 10.9 units on a scale | Standard Deviation 2.9 |
| Atacicept: Double-blind Period | Contrast Sensitivity: Score Line | Fellow eye: Week 12 (n = 15, 14) | 12.7 units on a scale | Standard Deviation 1.1 |
| Atacicept: Double-blind Period | Contrast Sensitivity: Score Line | Affected eye: Week 24 (n = 5, 5) | 11.2 units on a scale | Standard Deviation 1.6 |
| Atacicept: Double-blind Period | Contrast Sensitivity: Score Line | Fellow eye: Week 36 (n = 3, 3) | 13.3 units on a scale | Standard Deviation 0.6 |
| Atacicept: Double-blind Period | Contrast Sensitivity: Score Line | Affected eye: Week 36 (n = 3, 3) | 11.7 units on a scale | Standard Deviation 1.5 |
Secondary
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.
Time frame: Weeks 12, 24 and 36
Population: ITT population included all randomized participants. Here, N (number of participants analyzed) signifies those participants who were evaluable for this outcome measure and n signifies those participants who were evaluable for the specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo: Double-blind Period | Contrast Sensitivity: Total Number of Letters Correctly Identified | Fellow eye: Week 24 (n = 5, 5) | 36.2 letters | Standard Deviation 9.4 |
| Placebo: Double-blind Period | Contrast Sensitivity: Total Number of Letters Correctly Identified | Affected eye: Week 24 (n = 5, 5) | 34.2 letters | Standard Deviation 6.9 |
| Placebo: Double-blind Period | Contrast Sensitivity: Total Number of Letters Correctly Identified | Affected eye: Week 36 (n = 3, 3) | 37.0 letters | Standard Deviation 5.3 |
| Placebo: Double-blind Period | Contrast Sensitivity: Total Number of Letters Correctly Identified | Fellow eye: Week 12 (n = 15, 14) | 38.3 letters | Standard Deviation 4.1 |
| Placebo: Double-blind Period | Contrast Sensitivity: Total Number of Letters Correctly Identified | Fellow eye: Week 36 (n = 3, 3) | 39.7 letters | Standard Deviation 4 |
| Placebo: Double-blind Period | Contrast Sensitivity: Total Number of Letters Correctly Identified | Affected eye: Week 12 (n = 15, 14) | 35.4 letters | Standard Deviation 5.9 |
| Atacicept: Double-blind Period | Contrast Sensitivity: Total Number of Letters Correctly Identified | Fellow eye: Week 36 (n = 3, 3) | 40.0 letters | Standard Deviation 1 |
| Atacicept: Double-blind Period | Contrast Sensitivity: Total Number of Letters Correctly Identified | Affected eye: Week 12 (n = 15, 14) | 32.4 letters | Standard Deviation 8.8 |
| Atacicept: Double-blind Period | Contrast Sensitivity: Total Number of Letters Correctly Identified | Fellow eye: Week 24 (n = 5, 5) | 37.4 letters | Standard Deviation 2.4 |
| Atacicept: Double-blind Period | Contrast Sensitivity: Total Number of Letters Correctly Identified | Affected eye: Week 24 (n = 5, 5) | 33.0 letters | Standard Deviation 4.7 |
| Atacicept: Double-blind Period | Contrast Sensitivity: Total Number of Letters Correctly Identified | Fellow eye: Week 12 (n = 15, 14) | 37.6 letters | Standard Deviation 3.3 |
| Atacicept: Double-blind Period | Contrast Sensitivity: Total Number of Letters Correctly Identified | Affected eye: Week 36 (n = 3, 3) | 34.7 letters | Standard Deviation 3.2 |
Secondary
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.
Time frame: Weeks 12, 24 and 36
Population: ITT population included all randomized participants. Here, N (number of participants analyzed) signifies those participants who were evaluable for this outcome measure and n signifies those participants who were evaluable for the specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo: Double-blind Period | Difference in Retinal Nerve Fibre Layer (RNFL) Thickness Between the Affected Eye and Fellow Eye | Change at Week 36 (n = 3, 4) | -7.5 micrometer | Standard Error 8.8 |
| Placebo: Double-blind Period | Difference in Retinal Nerve Fibre Layer (RNFL) Thickness Between the Affected Eye and Fellow Eye | Change at Week 12 (n = 13, 13) | -14 micrometer | Standard Error 4 |
| Placebo: Double-blind Period | Difference in Retinal Nerve Fibre Layer (RNFL) Thickness Between the Affected Eye and Fellow Eye | Change at Week 24 (n = 4, 5) | -7 micrometer | Standard Error 6.9 |
| Atacicept: Double-blind Period | Difference in Retinal Nerve Fibre Layer (RNFL) Thickness Between the Affected Eye and Fellow Eye | Change at Week 24 (n = 4, 5) | -10.6 micrometer | Standard Error 3.7 |
| Atacicept: Double-blind Period | Difference in Retinal Nerve Fibre Layer (RNFL) Thickness Between the Affected Eye and Fellow Eye | Change at Week 12 (n = 13, 13) | -7.9 micrometer | Standard Error 1.5 |
| Atacicept: Double-blind Period | Difference in Retinal Nerve Fibre Layer (RNFL) Thickness Between the Affected Eye and Fellow Eye | Change at Week 36 (n = 3, 4) | -9.4 micrometer | Standard Error 6.6 |
Secondary
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.
Time frame: Weeks 12, 24 and 36
Population: ITT population included all randomized participants. Here, N (number of participants analyzed) signifies those participants who were evaluable for this outcome measure and n signifies those participants who were evaluable for the specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo: Double-blind Period | Low-Contrast Letter Acuity: Total Number of Letters Correctly Identified | Sloan chart 1.25%, affected eye: Week 12 (n=15,14) | 14.7 letters | Standard Deviation 14.7 |
| Placebo: Double-blind Period | Low-Contrast Letter Acuity: Total Number of Letters Correctly Identified | Sloan chart 1.25%, affected eye: Week 24 (n = 5,5) | 16.2 letters | Standard Deviation 13.6 |
| Placebo: Double-blind Period | Low-Contrast Letter Acuity: Total Number of Letters Correctly Identified | Sloan chart 1.25%, affected eye: Week 36 (n = 3,4) | 24.7 letters | Standard Deviation 8.1 |
| Placebo: Double-blind Period | Low-Contrast Letter Acuity: Total Number of Letters Correctly Identified | Sloan chart 2.5%, affected eye: Week 12 (n=15, 14) | 25.6 letters | Standard Deviation 16.7 |
| Placebo: Double-blind Period | Low-Contrast Letter Acuity: Total Number of Letters Correctly Identified | Sloan chart 2.5%, affected eye: Week 24 (n = 5, 5) | 26.8 letters | Standard Deviation 15.2 |
| Placebo: Double-blind Period | Low-Contrast Letter Acuity: Total Number of Letters Correctly Identified | Sloan chart 2.5%, affected eye: Week 36 (n = 3, 4) | 38.7 letters | Standard Deviation 4.7 |
| Placebo: Double-blind Period | Low-Contrast Letter Acuity: Total Number of Letters Correctly Identified | Sloan chart 1.25%, fellow eye: Week 12 (n=15,14) | 25.7 letters | Standard Deviation 13.1 |
| Placebo: Double-blind Period | Low-Contrast Letter Acuity: Total Number of Letters Correctly Identified | Sloan chart 1.25%, fellow eye: Week 24 (n = 5,5) | 22.2 letters | Standard Deviation 16.1 |
| Placebo: Double-blind Period | Low-Contrast Letter Acuity: Total Number of Letters Correctly Identified | Sloan chart 1.25%, fellow eye: Week 36 (n = 3,4) | 35.3 letters | Standard Deviation 4.2 |
| Placebo: Double-blind Period | Low-Contrast Letter Acuity: Total Number of Letters Correctly Identified | Sloan chart 2.5%, fellow eye: Week 12 (n=15, 14) | 35.3 letters | Standard Deviation 13.4 |
| Placebo: Double-blind Period | Low-Contrast Letter Acuity: Total Number of Letters Correctly Identified | Sloan chart 2.5%, fellow eye: Week 24 (n = 5, 5) | 33.6 letters | Standard Deviation 18.2 |
| Placebo: Double-blind Period | Low-Contrast Letter Acuity: Total Number of Letters Correctly Identified | Sloan chart 2.5%, fellow eye: Week 36 (n = 3, 4) | 45.7 letters | Standard Deviation 4.5 |
| Atacicept: Double-blind Period | Low-Contrast Letter Acuity: Total Number of Letters Correctly Identified | Sloan chart 2.5%, fellow eye: Week 24 (n = 5, 5) | 35.8 letters | Standard Deviation 15.4 |
| Atacicept: Double-blind Period | Low-Contrast Letter Acuity: Total Number of Letters Correctly Identified | Sloan chart 1.25%, affected eye: Week 12 (n=15,14) | 15.7 letters | Standard Deviation 19 |
| Atacicept: Double-blind Period | Low-Contrast Letter Acuity: Total Number of Letters Correctly Identified | Sloan chart 1.25%, fellow eye: Week 12 (n=15,14) | 25.9 letters | Standard Deviation 16.5 |
| Atacicept: Double-blind Period | Low-Contrast Letter Acuity: Total Number of Letters Correctly Identified | Sloan chart 1.25%, affected eye: Week 24 (n = 5,5) | 13.4 letters | Standard Deviation 18.4 |
| Atacicept: Double-blind Period | Low-Contrast Letter Acuity: Total Number of Letters Correctly Identified | Sloan chart 2.5%, fellow eye: Week 12 (n=15, 14) | 36.4 letters | Standard Deviation 12.7 |
| Atacicept: Double-blind Period | Low-Contrast Letter Acuity: Total Number of Letters Correctly Identified | Sloan chart 1.25%, affected eye: Week 36 (n = 3,4) | 9.8 letters | Standard Deviation 18.8 |
| Atacicept: Double-blind Period | Low-Contrast Letter Acuity: Total Number of Letters Correctly Identified | Sloan chart 1.25%, fellow eye: Week 24 (n = 5,5) | 24.6 letters | Standard Deviation 18.4 |
| Atacicept: Double-blind Period | Low-Contrast Letter Acuity: Total Number of Letters Correctly Identified | Sloan chart 2.5%, affected eye: Week 12 (n=15, 14) | 22.1 letters | Standard Deviation 19.5 |
| Atacicept: Double-blind Period | Low-Contrast Letter Acuity: Total Number of Letters Correctly Identified | Sloan chart 2.5%, fellow eye: Week 36 (n = 3, 4) | 32.5 letters | Standard Deviation 19.1 |
| Atacicept: Double-blind Period | Low-Contrast Letter Acuity: Total Number of Letters Correctly Identified | Sloan chart 2.5%, affected eye: Week 24 (n = 5, 5) | 21.4 letters | Standard Deviation 19.3 |
| Atacicept: Double-blind Period | Low-Contrast Letter Acuity: Total Number of Letters Correctly Identified | Sloan chart 1.25%, fellow eye: Week 36 (n = 3,4) | 19.8 letters | Standard Deviation 20.6 |
| Atacicept: Double-blind Period | Low-Contrast Letter Acuity: Total Number of Letters Correctly Identified | Sloan chart 2.5%, affected eye: Week 36 (n = 3, 4) | 20.3 letters | Standard Deviation 18.7 |
Secondary
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.
Time frame: From baseline (Study Day 1) up to Week 36
Population: ITT population included all randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo: Double-blind Period | Percentage of Participants Converting to Clinically Definite Multiple Sclerosis (CDMS) Second Clinical Attack | 17.6 percentage of participants |
| Atacicept: Double-blind Period | Percentage of Participants Converting to Clinically Definite Multiple Sclerosis (CDMS) Second Clinical Attack | 35.3 percentage of participants |