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Trial record 1 of 1 for:    NCT03315130
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Safety and Efficacy Study of RA101495 in Subjects With Generalized Myasthenia Gravis

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ClinicalTrials.gov Identifier: NCT03315130
Recruitment Status : Completed
First Posted : October 19, 2017
Results First Posted : June 27, 2022
Last Update Posted : July 27, 2022
Sponsor:
Information provided by (Responsible Party):
UCB Pharma ( Ra Pharmaceuticals )

Brief Summary:
The purpose of the study is to evaluate the safety and efficacy of RA101495 in patients with generalized Myasthenia Gravis (gMG). Subjects will be randomized in a 1:1:1 ratio to receive daily SC doses of 0.1 mg/kg RA101495, 0.3 mg/kg RA101495, or matching placebo for 12 weeks.

Condition or disease Intervention/treatment Phase
Generalized Myasthenia Gravis Drug: zilucoplan (RA101495) Drug: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 45 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Preliminary Efficacy of RA101495 in Subjects With Generalized Myasthenia Gravis
Actual Study Start Date : October 11, 2017
Actual Primary Completion Date : December 10, 2018
Actual Study Completion Date : November 19, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 0.1 mg/kg zilucoplan (RA101495) Drug: zilucoplan (RA101495)
Daily subcutaneous (SC) injection

Experimental: 0.3 mg/kg zilucoplan (RA101495) Drug: zilucoplan (RA101495)
Daily subcutaneous (SC) injection

Placebo Comparator: Placebo Drug: Placebo
Daily subcutaneous (SC) injection




Primary Outcome Measures :
  1. Main Portion: Change From Baseline to Week 12 in Quantitative Myasthenia Gravis (QMG) Score [ Time Frame: From Baseline to Week 12 ]
    The QMG is a standardized and validated quantitative strength scoring system that was developed specifically for myasthenia gravis (MG). The scale consists of 13 individual assessments, each scored on a 0-3 point scale (i.e., 0=none, 1=mild, 2=moderate, and 3=severe). The total score is the sum of the individual scores with a range of 0-39. Higher scores are representative of more severe impairment.


Secondary Outcome Measures :
  1. Main Portion: Change From Baseline to Week 12 in the Myasthenia Gravis - Activities of Daily Living (MG-ADL) Scale [ Time Frame: From Baseline to Week 12 ]
    The MG-ADL is a brief 8-item survey designed to evaluate MG symptom severity. The scale consists of 8 items each scored on a 0-3 point scale (i.e., 0=none, 1=mild, 2=moderate, and 3=severe). The total score is the sum of the 8 individual scores with range of 0-24. Higher scores are associated with more severe symptoms of MG.

  2. Main Portion: Change From Baseline to Week 12 in the Myasthenia Gravis - Quality of Life 15r (MG-QOL15r) Survey [ Time Frame: From Baseline to Week 12 ]
    The MG-QOL15r is a 15-item survey that was designed to assess quality of life in participants with MG. The survey consisted of 15 questions and the corresponding responses were each scored on a 0-2 point scale (0=Not much at all, 1=Somewhat, 2=Very Much). The total score is the sum of the 15 individual item scores with a range of 0-30. Higher scores indicate more severe impact of the disease on aspects of the participant's life.

  3. Main Portion: Change From Baseline to Week 12 in the MG Composite Scale Total Score [ Time Frame: From Baseline to Week 12 ]
    The MG Composite is a 10-item scale that has been used to measure the clinical status of participants with MG, in order to evaluate treatment response. It consists of 10 items which included ptosis (score range=0 to 3), double vision on lateral gaze left/right/both (score range=0 to 4), eye closure (score range=0 to 2), talking (score range=0 to 6), chewing (score range=0 to 6), swallowing (score range=0 to 6), breathing (score range=0 to 9), neck flexion or extension (score range=0 to 4), shoulder abduction (score range=0 to 5) and hip flexion (score range= 0 to 5). The total score is the sum of the 10 individual scores with a range of 0-50. Higher scores in the MG Composite indicate more severe impairment due to the disease.

  4. Main Portion: Percentage of Participants With >= 3-point Reduction in QMG Total Score at Week 12 [ Time Frame: Week 12 ]
    The QMG is a standardized and validated quantitative strength scoring system that was developed specifically for MG. The scale consists of 13 individual assessments, each scored on a 0-3 point scale (i.e., 0=none, 1=mild, 2=moderate, and 3=severe). The total score is the sum of the individual scores with a range of 0-39. Higher scores are representative of more severe impairment.

  5. Main Portion: Percentage of Participants Who Required Rescue Therapy Over the 12-week Treatment Period [ Time Frame: Up to Week 12 ]
    Percentage of participants who used at least 1 dose of rescue medication were reported.

  6. Main Portion: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: From Baseline to Week 12 ]
    An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A serious adverse event (SAE) is any untoward medical occurrence that at any dose resulted in death, life-threatening, significant or persistent disability/incapacity, congenital anomaly/birth defect, important medical event, initial inpatient hospitalization or prolongation of hospitalization.

  7. Main Portion: Change From Baseline in Sheep Red Blood Cell (sRBC) Lysis Assay at Week 12 (Pre-dose) [ Time Frame: Baseline and Week 12 (Pre-dose) ]
    A BioTek ELx800 automated microplate reader is used to measure the optical density at 415 nanometer (nm) of human plasma samples to calculate the percent lysis of sheep erythrocytes that has occurred as a result of total complement activity. The measure of complement activity is determined by the degree of hemolysis of the erythrocytes.

  8. Main Portion: Change From Baseline in C5 Levels at Week 12 (Pre-dose) [ Time Frame: Baseline and Week 12 (Pre-dose) ]
    Blood samples were collected from participants to assess Complement Component 5C levels.

  9. Main Portion: Plasma Concentration of RA101495 and Its Major Metabolites [ Time Frame: 1, 3 and 6 hours postdose on Day 1; Pre-dose on Week 1, 2, 4, 8 and 12 ]
    RA102758 and RA103488 are the metabolites of RA101495.

  10. Main Portion: Maximum Plasma Concentration (Cmax) on Day 1 [ Time Frame: Pre-dose, 1, 3 and 6 hours postdose on Day 1 ]
    Cmax is defined as the maximum observed plasma concentration.

  11. Main Portion: Time Corresponding to Cmax (Tmax) on Day 1 [ Time Frame: Pre-dose, 1, 3 and 6 hours postdose on Day 1 ]
    Tmax is defined as the time to observe maximum plasma concentration.

  12. Main Portion: Metabolites (RA102758 and RA103488) to Parent Ratio [ Time Frame: Pre-dose, 1, 3 and 6 hours postdose on Day 1; Pre-dose on Week 1, 2, 4, 8 and 12 ]
    RA102758 and RA103488 are the metabolites of RA101495.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of gMG [Myasthenia Gravis Foundation of America (MGFA) Class II-IVa] at Screening
  • Positive serology for acetylcholine receptor (AChR) autoantibodies
  • QMG score ≥ 12 at Screening and Randomization
  • No change in corticosteroid dose for at least 30 days prior to Randomization or anticipated to occur during the 12-week Treatment Period
  • No change in immunosuppressive therapy, including dose, for at least 30 days prior to Randomization or anticipated to occur during the 12-week Treatment Period

Exclusion Criteria:

  • Thymectomy within 6 months prior to Randomization or scheduled to occur during the 12 week Treatment Period
  • History of meningococcal disease
  • Current or recent systemic infection within 2 weeks prior to Randomization or infection requiring intravenous (IV) antibiotics within 4 weeks prior to Randomization

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): NCT03315130


Locations
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Sponsors and Collaborators
Ra Pharmaceuticals
Investigators
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Study Director: UCB Cares 001 844 599 2273 (UCB)
  Study Documents (Full-Text)

Documents provided by UCB Pharma ( Ra Pharmaceuticals ):
Study Protocol  [PDF] April 10, 2019
Statistical Analysis Plan  [PDF] March 5, 2020

Publications of Results:
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Responsible Party: Ra Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03315130    
Other Study ID Numbers: RA101495-02.201
First Posted: October 19, 2017    Key Record Dates
Results First Posted: June 27, 2022
Last Update Posted: July 27, 2022
Last Verified: July 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Myasthenia Gravis
Muscle Weakness
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Pathologic Processes
Paraneoplastic Syndromes, Nervous System
Nervous System Neoplasms
Neoplasms by Site
Neoplasms
Paraneoplastic Syndromes
Autoimmune Diseases of the Nervous System
Neurodegenerative Diseases
Neuromuscular Junction Diseases
Neuromuscular Diseases
Autoimmune Diseases
Immune System Diseases