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

Neuromyelitis Optica Clinical Trial

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04201262
• Other study ID #: ALXN1210-NMO-307
• Secondary ID: CHAMPION-NMO-307
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: December 13, 2019
• Est. completion date: July 31, 2024

Study information

• Verified date: July 2023
• Source: Alexion
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary purpose of this study is to evaluate the efficacy and safety of ravulizumab for the treatment of adult participants with NMOSD.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 58
• Est. completion date: July 31, 2024
• Est. primary completion date: March 15, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• 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.

Locations

Country	Name	City	State
Australia	Clinical Study Site	Camperdown	New South Wales
Australia	Clinical Study Site	Fitzroy
Australia	Clinical Study Site	New Lambton Heights	New South Wales
Australia	Clinical Study Site	Parkville	Victoria
Austria	Clinical Study Site	Wien
Canada	Clinical Study Site	Burnaby	British Columbia
Canada	Clinical Study Site	Edmonton
Denmark	Clinical Study Site	Aarhus
France	Clinical Study Site	Bron Cedex
France	Clinical Study Site	Montpellier
France	Clinical Study Site	Nîmes
France	Clinical Study Site	Strasbourg
Germany	Clinical Study Site	Berlin
Germany	Clinical Study Site	Dresden
Germany	Clinical Study Site	Leipzig
Germany	Clinical Study Site	Muenchen
Italy	Clinical Study Site	Cefalu
Italy	Clinical Study Site	Gallarate
Italy	Clinical Study Site	Napoli
Italy	Clinical Study Site	Orbassano
Italy	Clinical Study Site	Roma
Italy	Clinical Study Site	Roma
Japan	Clinical Study Site	Chiba
Japan	Clinical Study Site	Fukuoka-shi
Japan	Clinical Study Site	Kawagoe-shi
Japan	Clinical Study Site	Niigata-shi
Japan	Clinical Study Site	Sendai
Japan	Clinical Study Site	Sendai-shi
Korea, Republic of	Clinical Study Site	Goyang-si
Korea, Republic of	Clinical Study Site	Seoul
Korea, Republic of	Clinical Study Site	Seoul
Korea, Republic of	Clinical Study Site	Seoul
Korea, Republic of	Clinical Study Site	Seoul
Korea, Republic of	Clinical Study Site	Seoul
Korea, Republic of	Clinical Study Site	Seoul
Poland	Clinical Study Site	Katowice
Poland	Clinical Study Site	Katowice
Poland	Clinical Study Site	Lodz
Spain	Clinical Study Site	Barakaldo
Spain	Clinical Study Site	Barcelona
Spain	Clinical Study Site	Barcelona
Spain	Clinical Study Site	Madrid
Spain	Clinical Study Site	Madrid
Spain	Clinical Study Site	Malaga
Spain	Clinical Study Site	Valencia
United Kingdom	Clinical Study Site	Liverpool
United Kingdom	Clinical Study Site	Oxford
United States	Clinical Study Site	Atlanta	Georgia
United States	Clinical Study Site	Aurora	Colorado
United States	Clinical Study Site	Birmingham	Alabama
United States	Clinical Study Site	Boston	Massachusetts
United States	Clinical Study Site	Carlsbad	California
United States	Clinical Study Site	Chapel Hill	North Carolina
United States	Clinical Study Site	Cincinnati	Ohio
United States	Clinical Study Site	Dallas	Texas
United States	Clinical Study Site	Fort Collins	Colorado
United States	Clinical Study Site	Houston	Texas
United States	Clinical Study Site	Jackson	Mississippi
United States	Clinical Study Site	Kansas City	Kansas
United States	Clinical Study Site	Lexington	Kentucky
United States	Clinical Study Site	Miami	Florida
United States	Clinical Study Site	Mobile	Alabama
United States	Clinical Study Site	Rochester	Minnesota
United States	Clinical Study Site	Rolling Meadows	Illinois
United States	Clinical Study Site	Round Rock	Texas
United States	Clinical Study Site	Saint Louis	Missouri
United States	Clinical Study Site	Washington	District of Columbia
United States	Clinical Study Site	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Alexion

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Canada,  Denmark,  France,  Germany,  Italy,  Japan,  Korea, Republic of,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With an Adjudicated On-trial Relapse in 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.	Baseline up to 2.25 years (end of the Primary Treatment Period)
Secondary	Adjudicated On-trial Annualized Relapse Rate (ARR) in 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.	Baseline up to 2.25 years (end of the Primary Treatment Period)
Secondary	Number of Participants With Clinically Important Change From Baseline in Hauser Ambulation Index (HAI) Score at the End of 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.	Baseline up to 2.25 years (end of the Primary Treatment Period)
Secondary	Change From Baseline in European Quality of Life Health 5-dimension Questionnaire (EQ-5D) Index Score at the End of 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.	Baseline, up to 2.25 years (end of the Primary Treatment Period)
Secondary	Change From Baseline in EQ-5D Visual Analog Scale (VAS) Score at the End of 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.	Baseline, up to 2.25 years (end of the Primary Treatment Period)
Secondary	Number of Participants With Clinically Important Worsening From Baseline in Expanded Disability Status Scale (EDSS) Score at the End of 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.	Baseline up to 2.25 years (end of the Primary Treatment Period)
Secondary	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	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.	Baseline up to 2.25 years (end of the Primary Treatment Period)
Secondary	Serum Ravulizumab Concentration		Predose and end of infusion (EOI) at Week 26
Secondary	Change From Baseline in Serum Free C5 Concentration at Week 26 and 50		Baseline, Week 26 (Predose and EOI)
Secondary	Number of Participants With Anti-drug Antibodies (ADAs) During the Primary Treatment Period		Baseline, Weeks 26, 50, 82, and 106