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Efficacy and Safety of BIIB033 (Opicinumab) as an Add-on Therapy to Disease-Modifying Therapies (DMTs) in Relapsing Multiple Sclerosis (MS) (AFFINITY)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03222973
Recruitment Status : Active, not recruiting
First Posted : July 19, 2017
Last Update Posted : December 17, 2019
Sponsor:
Information provided by (Responsible Party):
Biogen

Brief Summary:

The primary objective of Part 1 of this study is to evaluate the effects of BIIB033 versus placebo on disability improvement over 72 weeks. The primary objective of Part 2 of this study is to evaluate the long-term safety profile of BIIB033 as an add-on therapy in participants with MS.

The secondary objective of Part 1 is to evaluate the effects of BIIB033 versus placebo on additional measures of disability improvement. The secondary objective of Part 2 is to investigate long-term efficacy (disability improvement) and additional safety measures of BIIB033 as an add-on therapy in participants with MS.


Condition or disease Intervention/treatment Phase
Multiple Sclerosis Drug: BIIB033 (opicinumab) Drug: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 263 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study With Optional Open-Label Extension in Subjects With Relapsing Multiple Sclerosis to Evaluate the Efficacy and Safety of BIIB033 as an Add-On Therapy to Anti-Inflammatory Disease-Modifying Therapies
Actual Study Start Date : November 14, 2017
Estimated Primary Completion Date : March 3, 2022
Estimated Study Completion Date : May 26, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: BIIB033 (opicinumab) 750 mg
Participants with relapsing multiple sclerosis (RMS) will receive BIIB033 750 milligram (mg) intravenously (IV) as an add-on therapy to a background disease-modifying therapy (DMT) once every 4 weeks over 72 weeks in Part 1 and once every 4 weeks over 96 weeks in Part 2.
Drug: BIIB033 (opicinumab)
Administered as specified in the treatment arm

Placebo Comparator: Placebo
Participants with RMS will receive placebo IV as an add-on therapy to a background DMT once every 4 weeks over 72 weeks in Part 1 and BIIB033 once every 4 weeks over 96 weeks in Part 2. The placebo looks like BIIB033 but does not contain the active ingredient that is thought to have an effect on MS disease. The placebo used in this study is sterile normal saline (water with a small amount of sodium chloride [salt]).
Drug: Placebo
Administered as specified in the treatment arm




Primary Outcome Measures :
  1. Overall Response Score [ Time Frame: Part 1: Assessed every 12 weeks from Baseline to Week 72 ]
    Overall Response Score is a multicomponent score based on 4 components: Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW), 9-Hole Peg Test in the dominant hand (9HPT-D), and 9HPT in the nondominant hand (9HPT-ND). It assesses overall changes in disability over time. Overall Score ranges from +4 to -4. At each visit, each component is given a score relative to baseline: -1 if threshold is met for worsening, 0 if no changes meet threshold criteria, or +1 if threshold is met for improvement. The thresholds for T25FW and 9HPT are defined by a 15% change from baseline (≥15% decrease from baseline for improvement and ≥15% increase from baseline for worsening). For EDSS, improvement is defined as a ≥1.0-point decrease in EDSS from a baseline score of ≤6.0, and worsening is defined as a ≥1-point increase from a baseline score of ≤5.5 or a ≥0.5-point increase from a baseline score equal to 6.0.

  2. Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Part 2: Baseline to Week 96 ]
    An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable andunintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A SAE is any untoward medical occurrence that at any dose results in death, life-threatening event, requires inpatient hospitalization, significant disability/incapacity or congenital anomaly.


Secondary Outcome Measures :
  1. Percentage of Participants with 12-week Confirmed Improvement in at least 1 of the Following Assessments: EDSS, T25FW, 9HPT-D, or 9HPT-ND [ Time Frame: Part 1: Assessed every 12 weeks from Baseline to Week 72 ]
    EDSS measures disability status on a scale ranging from 0 to 10, with higher scores indicating more disability. Scoring is based on measures of impairment in eight functional systems on examination by a neurologist. The T25FW is a quantitative mobility and leg function performance test based on a timed walk over 25 feet. The score for the T25FW is averaged between two completed trials. The 9HPT is a quantitative test of upper extremity function that measures the time it takes to place 9 pegs into 9 holes and then remove the pegs.

  2. Percentage of Participants with 12-week Confirmed Improvement in at least 1 of the Following Assessments: EDSS, T25FW, 9HPT-D, 9HPT-ND, or 3-Second Paced Auditory Serial Addition Test (PASAT-3) [ Time Frame: Part 1: Assessed every 12 weeks from Baseline to Week 72 ]

    EDSS measures disability status on a scale ranging from 0 to 10, with higher scores indicating more disability. Scoring is based on measures of impairment in eight functional systems on examination by a neurologist. The T25FW is a quantitative mobility and leg function performance test based on a timed walk over 25 feet. The score for the T25FW is averaged between two completed trials. The 9HPT is a quantitative test of upper extremity function that measures the time it takes to place 9 pegs into 9 holes and then remove the pegs.

    The PASAT assesses auditory information processing speed. A random series of numbers from 1 to 9, inclusive, are presented and the participant is instructed to consecutively add pairs of numbers so that each number is added to the one that immediately preceded it. In the 3- second PASAT, numbers are presented at a rate of 1 every 3 seconds.


  3. Percentage of Participants with 12-week Confirmed Improvement in at least 1 of the Following Assessments: EDSS, T25FW, 9HPT-D, or 9HPT-ND, and without confirmed worsening in any of the 4 assessments during the 72 weeks of the study [ Time Frame: Part 1: Assessed every 12 weeks from Baseline to Week 72 ]
    EDSS measures disability status on a scale ranging from 0 to 10, with higher scores indicating more disability. Scoring is based on measures of impairment in eight functional systems on examination by a neurologist. The T25FW is a quantitative mobility and leg function performance test based on a timed walk over 25 feet. The score for the T25FW is averaged between two completed trials. The 9HPT is a quantitative test of upper extremity function that measures the time it takes to place 9 pegs into 9 holes and then remove the pegs.

  4. Percentage of Participants with 12-week Confirmed Improvement in at least 1 of the Following Assessments: EDSS, T25FW, 9HPT-D, 9HPT-ND, and Symbol Digit Modalities Test (SDMT) [ Time Frame: Part 1: Assessed every 12 weeks from Baseline to Week 72 ]

    EDSS measures disability status on a scale ranging from 0 to 10, with higher scores indicating more disability. Scoring is based on measures of impairment in eight functional systems on examination by a neurologist. The T25FW is a quantitative mobility and leg function performance test based on a timed walk over 25 feet. The score for the T25FW is averaged between two completed trials. The 9HPT is a quantitative test of upper extremity function that measures the time it takes to place 9 pegs into 9 holes and then remove the pegs.

    The SDMT measures the time to pair abstract geometric symbols with specific numbers. The score is the number of correctly coded items from 0-110 in 90 seconds.


  5. Percentage of Participants with 12-week Confirmed Improvement in at least 1 of the Following Assessments: EDSS, T25FW, 9HPT-D, or 9HPT-ND (20% thresholds for T25FW and 9HPT) [ Time Frame: Part 1: Assessed every 12 weeks from Baseline to Week 72 ]
    EDSS measures disability status on a scale ranging from 0 to 10, with higher scores indicating more disability. Scoring is based on measures of impairment in eight functional systems on examination by a neurologist. The T25FW is a quantitative mobility and leg function performance test based on a timed walk over 25 feet. The score for the T25FW is averaged between two completed trials. The 9HPT is a quantitative test of upper extremity function that measures the time it takes to place 9 pegs into 9 holes and then remove the pegs.

  6. Overall Response Score [ Time Frame: Part 2: Assessed every 24 weeks from Baseline to Week 96 ]
    Overall Response Score is a multicomponent score based on 4 components: EDSS, T25FW, 9HPT-D, and 9HPT-ND. It assesses overall changes in disability over time. Overall Score ranges from +4 to -4. At each visit, each component is given a score relative to baseline: -1 if threshold is met for worsening, 0 if no changes meet threshold criteria, or +1 if threshold is met for improvement. The thresholds for T25FW and 9HPT are defined by a 15% change from baseline (≥15% decrease from baseline for improvement and ≥15% increase from baseline for worsening). For EDSS, improvement is defined as a ≥1.0-point decrease in EDSS from a baseline score of ≤6.0, and worsening is defined as a ≥1-point increase from a baseline score of ≤5.5 or a ≥0.5-point increase from a baseline score equal to 6.0.

  7. Percentage of Participants with 24-week Confirmed Improvement in at least 1 of the Following Assessments: EDSS, T25FW, 9HPT-D, or 9HPT-ND [ Time Frame: Part 2: Assessed every 24 weeks from Baseline to Week 108 ]
    EDSS measures disability status on a scale ranging from 0 to 10, with higher scores indicating more disability. Scoring is based on measures of impairment in eight functional systems on examination by a neurologist. The T25FW is a quantitative mobility and leg function performance test based on a timed walk over 25 feet. The score for the T25FW is averaged between two completed trials. The 9HPT is a quantitative test of upper extremity function that measures the time it takes to place 9 pegs into 9 holes and then remove the pegs.

  8. Percentage of Participants with 24-week Confirmed Improvement in at least 1 of the Following Assessments: EDSS, T25FW, 9HPT-D, 9HPT-ND, or 3-Second Paced Auditory Serial Addition Test (PASAT-3) [ Time Frame: Part 2: Assessed every 24 weeks from Baseline to Week 108 ]

    EDSS measures disability status on a scale ranging from 0 to 10, with higher scores indicating more disability. Scoring is based on measures of impairment in eight functional systems on examination by a neurologist. The T25FW is a quantitative mobility and leg function performance test based on a timed walk over 25 feet. The score for the T25FW is averaged between two completed trials. The 9HPT is a quantitative test of upper extremity function that measures the time it takes to place 9 pegs into 9 holes and then remove the pegs.

    The PASAT assesses auditory information processing speed. A random series of numbers from 1 to 9, inclusive, are presented and the participant is instructed to consecutively add pairs of numbers so that each number is added to the one that immediately preceded it. In the 3- second PASAT, numbers are presented at a rate of 1 every 3 seconds.


  9. Percentage of Participants with 24-week Confirmed Improvement in at least 1 of the Following Assessments: EDSS, T25FW, 9HPT-D, or 9HPT-ND, and without confirmed worsening in any of the 4 assessments during the 96 weeks of the study [ Time Frame: Part 2: Assessed every 24 weeks from Baseline to Week 96 ]
    EDSS measures disability status on a scale ranging from 0 to 10, with higher scores indicating more disability. Scoring is based on measures of impairment in eight functional systems on examination by a neurologist. The T25FW is a quantitative mobility and leg function performance test based on a timed walk over 25 feet. The score for the T25FW is averaged between two completed trials. The 9HPT is a quantitative test of upper extremity function that measures the time it takes to place 9 pegs into 9 holes and then remove the pegs.

  10. Percentage of Participants with 24-week Confirmed Improvement in at least 1 of the Following Assessments: EDSS, T25FW, 9HPT-D, 9HPT-ND, and Symbol Digit Modalities Test (SDMT) [ Time Frame: Part 2: Assessed every 24 weeks from Baseline to Week 108 ]

    EDSS measures disability status on a scale ranging from 0 to 10, with higher scores indicating more disability. Scoring is based on measures of impairment in eight functional systems on examination by a neurologist. The T25FW is a quantitative mobility and leg function performance test based on a timed walk over 25 feet. The score for the T25FW is averaged between two completed trials. The 9HPT is a quantitative test of upper extremity function that measures the time it takes to place 9 pegs into 9 holes and then remove the pegs.

    The SDMT measures the time to pair abstract geometric symbols with specific numbers. The score is the number of correctly coded items from 0-110 in 90 seconds.


  11. Percentage of Participants with 24-week Confirmed Improvement in at least 1 of the Following Assessments: EDSS, T25FW, 9HPT-D, or 9HPT-ND (20% thresholds for T25FW and 9HPT) [ Time Frame: Part 2: Assessed every 24 weeks from Baseline to Week 108 ]
    EDSS measures disability status on a scale ranging from 0 to 10, with higher scores indicating more disability. Scoring is based on measures of impairment in eight functional systems on examination by a neurologist. The T25FW is a quantitative mobility and leg function performance test based on a timed walk over 25 feet. The score for the T25FW is averaged between two completed trials. The 9HPT is a quantitative test of upper extremity function that measures the time it takes to place 9 pegs into 9 holes and then remove the pegs.

  12. Percentage of Participants with Potentially Clinically Significant Abnormal Laboratory Values [ Time Frame: Part 2: Baseline to Week 96 ]
    Laboratory assessments including hematology, blood chemistry, urinalysis and serum and urine pregnancy test only for women of childbearing potential, will be evaluated for safety.

  13. Percentage of Participants with Potentially Clinically Significant Electrocardiogram (ECG) Values [ Time Frame: Part 2: Assessed every 12 weeks from Baseline to Week 96 ]
    ECG measurements will be taken for participants for evaluating safety.

  14. Percentage of Participants with Potentially Clinically Significant Abnormal Vital Signs Values [ Time Frame: Part 2: Baseline to Week 96 ]
    Vital sign measurements including temperature, pulse rate, systolic and diastolic blood pressure, and respiratory rate will be evaluated for safety.

  15. Percentage of Participants with Potentially Clinically Significant Abnormal Weight Values [ Time Frame: Part 2: Baseline, Week 12, 24, 36, 48, 72 and 96 ]
    Body weight measurements will be taken for participants for evaluating safety.

  16. Columbia Suicide Severity Rating Scale (C-SSRS) Score [ Time Frame: Part 2: Assessed every 24 weeks from Baseline to Week 96 ]
    C-SSRS is a suicidal ideation and behavior rating scale. It rates an individual's degree of suicidal ideation on a scale, ranging from "wish to be dead" to "active suicidal ideation with specific plan and intent and behaviors". The scale identifies specific behaviors which may be indicative of an individual's intent to complete suicide.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 58 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria: Part 1

  • Baseline Expanded Disability Status Scale (EDSS) of 2.0 to 6.0, have a diagnosis of relapsing-remitting multiple sclerosis (RRMS) per the 2010 McDonald's criteria or onset of secondary progressive multiple sclerosis (SPMS) per the Lublin and Reingold criteria, and should have experienced their first MS symptom(s) within the previous 20 years.
  • Subjects must have experienced at least 1 of the following within 24 months prior to Day 1/Baseline: a clinical relapse (but not within 24 weeks prior to Day 1/Baseline), gadolinium-enhancing lesions on brain or spinal cord magnetic resonance imaging (MRI), or new T2 lesion(s) on brain or spinal cord MRI.
  • Subjects must be on a stable dose of a protocol-specified anti-inflammatory disease-modifying therapy (DMT) (IFNβ [Avonex, Plegridy, Betaferon/Betaseron, or Rebif], dimethyl fumarate (DMF) [Tecfidera], or natalizumab [Tysabri]) for at least 24 weeks prior to enrollment.
  • In addition, subjects must have met protocol-defined MRI characteristics using magnetization transfer ratio (MTR) and diffusion tensor imaging (DTI) sequences at Screening/Baseline.

Key Inclusion Criteria: Part 2

-Subjects who complete study treatment (BIIB033 or placebo) at Part 1/Week 72 Visit.

Key Exclusion Criteria: Part 1

  • Primary progressive MS
  • An MS relapse that has occurred within 24 weeks prior to Day 1/Baseline or the subject has not stabilized from a previous relapse at the time of Screening.
  • Treatment with any chemotherapeutic agents (e.g., mitoxantrone, cyclophosphamide, cladribine), cell-depleting monoclonal antibodies (mAbs) (e.g., rituximab, ocrelizumab, alemtuzumab), total lymphoid irradiation, T-cell or T-cell receptor vaccination, or teriflunomide within 1 year prior to Day 1/Baseline.
  • Treatment with other anti-inflammatory DMTs (e.g., GA, fingolimod, daclizumab) or plasmapheresis within 24 weeks prior to Day1/Baseline.
  • Treatment with Botox for limb spasticity within 24 weeks before Day 1/Baseline.
  • Contraindications to MRI, for example, presence of pacemakers or other implanted metal devices (excluding dental braces), an allergy to gadolinium renal impairment, or claustrophobia that cannot be medically managed.
  • History of human immunodeficiency virus or other immunodeficient conditions.
  • History of malignancy; however, subjects with a history of excised or treated basal cell carcinoma or fewer than 3 squamous cell carcinomas are eligible to participate in this study.

Key Exclusion Criteria: Part 2

  • Subjects who did not complete study treatment in Part 1/Week 72 Visit
  • Subjects who have a duration >12 weeks between their Part 1/Week 72 Visit and Part 2/Day 1.
  • Contraindications to MRI, for example, presence of pacemakers or other implanted metal devices (excluding dental braces), an allergy to Gd, renal impairment, or claustrophobia that cannot be medically managed.
  • History of human immunodeficiency virus or other immunodeficient conditions not related to DMT treatment.
  • History of malignancy unless enrollment is approved by the Sponsor; subjects with a history of excised or treated basal cell carcinoma or fewer than 3 squamous cell carcinomas are eligible to participate in this study.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply


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): NCT03222973


Locations
Show Show 159 study locations
Sponsors and Collaborators
Biogen
Investigators
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Study Director: Medical Director Biogen

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Biogen
ClinicalTrials.gov Identifier: NCT03222973    
Other Study ID Numbers: 215MS202
2017-001224-22 ( EudraCT Number )
First Posted: July 19, 2017    Key Record Dates
Last Update Posted: December 17, 2019
Last Verified: December 2019

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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 Biogen:
Remyelination
Re-myelination
DMT
LINGO-1
Anti-LINGO-1
Opicinumab
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