An Efficacy and Safety Study of Ravulizumab in Adult Participants With NMOSD

• ClinicalTrials.gov Identifier: NCT04201262
• Recruitment Status: Active, not recruiting
• First Posted: December 17, 2019
• Results First Posted: August 9, 2023
• Last Update Posted: August 9, 2023
• Sponsor: Alexion Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Alexion Pharmaceuticals, Inc.

Tracking Information

• First Submitted Date: December 11, 2019
• First Posted Date: December 17, 2019
• Results First Submitted Date: May 31, 2023
• Results First Posted Date: August 9, 2023
• Last Update Posted Date: August 9, 2023
• Actual Study Start Date: December 13, 2019
• Actual Primary Completion Date: March 15, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 17, 2023)

Number of Participants With an Adjudicated On-trial Relapse in the Primary Treatment Period [ Time Frame: Baseline up to 2.25 years (end of the Primary Treatment Period) ]

An On-trial Relapse was defined as a new onset of neurologic symptoms or worsening of existing neurologic symptoms with an objective change (clinical sign) on neurologic examination that persisted for more than 24 hours as confirmed by the treating physician. An adjudicated On-trial Relapse was defined by the protocol and positively adjudicated by the independent relapse adjudication committee.

• Original Primary Outcome Measures (submitted: December 13, 2019): Time To First Adjudicated On-Trial Relapse [ Time Frame: Baseline, up to 2 years (end of the Primary Treatment Period) ]

Current Secondary Outcome Measures (submitted: July 17, 2023)

• Adjudicated On-trial Annualized Relapse Rate (ARR) in the Primary Treatment Period [ Time Frame: Baseline up to 2.25 years (end of the Primary Treatment Period) ]
  The adjudicated On-trial ARR was computed as the total number of relapses divided by the total number of participant years in the study period. A central independent committee was used to adjudicate all On-trial Relapses as determined by the treating physician. Results reported as adjusted adjudicated On-trial ARR based on a Poisson regression centered on the mean historical ARR in the 24 months prior to screening.
• Number of Participants With Clinically Important Change From Baseline in Hauser Ambulation Index (HAI) Score at the End of Primary Treatment Period [ Time Frame: Baseline up to 2.25 years (end of the Primary Treatment Period) ]
  The HAI is a rating scale developed to assess mobility by evaluating the time and degree of assistance required to walk 25 feet. The scale ranges from 0 to 9, with 0 being the best score (asymptomatic; fully ambulatory with no assistance) and 9 being the worst (restricted to wheelchair; unable to transfer self independently). Clinically important change is conditional on the baseline value: worsening if the baseline HAI is 0 and at least 2 points increase or if the baseline HAI is >0 and at least 1 point increase; improvement if the baseline value is at least 2 and at least 1 point decrease; and stable if baseline is 0 or 1 and a 0- or 1-point increase or decrease or baseline is at least 2 and not change.
• Change From Baseline in European Quality of Life Health 5-dimension Questionnaire (EQ-5D) Index Score at the End of Primary Treatment Period [ Time Frame: Baseline, up to 2.25 years (end of the Primary Treatment Period) ]
  The EQ-5D is a generic, standardized, self-administered instrument that provides a simple, descriptive profile and a single index value for health status. It consists of 2 parts; the EQ-5D descriptive system and the EQ-5D visual analogue scale (VAS). The EQ-5D descriptive system includes 5 dimensions; mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension measured on 3 levels: "no problem" (level 1), "some problems" (level 2), "extreme problems" (level 3). The digits for 5 dimensions can be combined in a 5-digit number describing the respondent's health state. The 5 dimensional 3-level systems was converted into single index utility score that ranges from less than 0 to 1, with higher scores representing a better health status.
• Change From Baseline in EQ-5D Visual Analog Scale (VAS) Score at the End of Primary Treatment Period [ Time Frame: Baseline, up to 2.25 years (end of the Primary Treatment Period) ]
  The EQ-5D is a generic, standardized, self-administered instrument that provides a simple, descriptive profile and a single index value for health status. It consists of 2 parts; the EQ-5D descriptive system and the EQ-5D visual analogue scale (VAS). The EQ-5D VAS is an overall health state scale where the participant selects a number between 0 to 100 to describe the condition of their health, with 100 being 'The best health state you can imagine' and 0 being 'The worst health state you can imagine'. An increase in score indicates improvement.
• Number of Participants With Clinically Important Worsening From Baseline in Expanded Disability Status Scale (EDSS) Score at the End of Primary Treatment Period [ Time Frame: Baseline up to 2.25 years (end of the Primary Treatment Period) ]
  Disease-related disability was measured by the EDSS. The EDSS is an ordinal clinical rating scale that ranges from 0 (normal neurologic examination) to 10 (death) in half-point increments. Clinically important worsening was defined as an increase in EDSS score conditional on the baseline value: If the baseline EDSS was 0 and at least 2-point increase; if the baseline is 1 to 5, and at least 1-point increase; if the baseline is > 5 and at least 0.5 increase.
• Number of Participants With Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Serious Adverse Events (TESAEs), and TEAEs Leading to Study Drug Discontinuation in the Primary Treatment Period [ Time Frame: Baseline up to 2.25 years (end of the Primary Treatment Period) ]
  An AE was as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An SAE was an AE that met at least 1 of the following criteria: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization for the AE, persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, congenital anomaly/birth defect (in the child of a participant who was exposed to the study drug), important medical event or reaction. TEAEs were AEs with a start date on or after the date of the first dose of study drug. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
• Serum Ravulizumab Concentration [ Time Frame: Predose and end of infusion (EOI) at Week 26 ]
• Change From Baseline in Serum Free C5 Concentration at Week 26 and 50 [ Time Frame: Baseline, Week 26 (Predose and EOI) ]
• Number of Participants With Anti-drug Antibodies (ADAs) During the Primary Treatment Period [ Time Frame: Baseline, Weeks 26, 50, 82, and 106 ]

Original Secondary Outcome Measures (submitted: December 13, 2019)

• Incidence Of Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Serious Adverse Events, And TEAEs Leading To Study Drug Discontinuation [ Time Frame: Baseline, up to 2 years (end of the Primary Treatment Period) ]
• Adjudicated On-Trial Annualized Relapse Rate [ Time Frame: Baseline, up to 2 years (end of the Primary Treatment Period) ]
• Clinically Important Worsening In Expanded Disability Status Scale [ Time Frame: Baseline, up to 2 years (end of the Primary Treatment Period) ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: An Efficacy and Safety Study of Ravulizumab in Adult Participants With NMOSD
• Official Title: A Phase 3, External Placebo-Controlled, Open-Label, Multicenter Study to Evaluate the Efficacy and Safety of Ravulizumab in Adult Patients With Neuromyelitis Optica Spectrum Disorder (NMOSD)
• Brief Summary: The primary purpose of this study is to evaluate the efficacy and safety of ravulizumab for the treatment of adult participants with NMOSD.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:

External Placebo-Controlled, Open-Label Design

Masking: None (Open Label)
Primary Purpose: Treatment

Condition

• Neuromyelitis Optica
• Neuromyelitis Optica Spectrum Disorder

Intervention

Biological: Ravulizumab

Participants will receive a weight-based loading dose of ravulizumab via IV infusion on Day 1, followed by weight-based maintenance doses on Day 15, then once every 8 weeks until end of the Long-Term Extension Period.

Other Names:

• ALXN1210
• Ultomiris

Study Arms

Experimental: Ravulizumab

During the Primary Treatment Period, all participants will receive open-label ravulizumab via intravenous (IV) infusion starting on Day 1. The end of the Primary Treatment Period will be triggered when the last enrolled participant completes between 26 and 50 weeks in the study (depending on the number of adjudicated On-Trial Relapse observed).

After completion of the Primary Treatment Period, all participants will have the opportunity to continue receiving ravulizumab in the Long-Term Extension Period of the study. For each participant, the Long-Term Extension Period continues for up to 2 years, or until ravulizumab is approved and/or available (in accordance with country-specific regulations), whichever occurs first.

Intervention: Biological: Ravulizumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: April 13, 2021): 58
• Original Estimated Enrollment (submitted: December 13, 2019): 55
• Estimated Study Completion Date: July 31, 2024
• Actual Primary Completion Date: March 15, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Anti-aquaporin-4 antibody-positive and a diagnosis of NMOSD as defined by the 2015 international consensus diagnostic criteria.
2. At least 1 attack or relapse in the last 12 months prior to the Screening Period.
3. Expanded Disability Status Scale score ≤7.
4. Participants who enter the study receiving supportive immunosuppressive therapy must be on a stable dosing regimen of adequate duration prior to Screening.
5. Body weight ≥40 kilograms.
6. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

Exclusion Criteria:

1. History of neisseria meningitidis infection.
2. Human immunodeficiency virus (HIV) infection (evidenced by HIV-1 or HIV-2 antibody titer).
3. Previously or currently treated with a complement inhibitor.
4. Use of rituximab or mitoxantrone within 3 months prior to Screening.
5. Use of IV immunoglobulin within 3 weeks prior to Screening.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Austria, Canada, Denmark, France, Germany, Italy, Japan, Korea, Republic of, Poland, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT04201262
• Other Study ID Numbers: ALXN1210-NMO-307; CHAMPION-NMO-307 ( Other Identifier: Alexion Pharmaceuticals )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes

• Current Responsible Party: Alexion Pharmaceuticals, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Alexion Pharmaceuticals, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Alexion Pharmaceuticals, Inc.
• Verification Date: July 2023