Trial Outcomes & Findings for A Study of the Safety and Activity of Eculizumab in Pediatric Participants With Relapsing Neuromyelitis Optica Spectrum Disorder (NCT NCT04155424)

Last Updated: 2024-09-25

Results Overview

ARR was calculated as the number of relapses for each participant divided by the number of years of treatment for that participant. Baseline ARR was based on 24 months prior to screening.

Recruitment status

TERMINATED

Study phase

PHASE2/PHASE3

Target enrollment

5 participants

Primary outcome timeframe

Baseline, Week 52/53

Results posted on

2024-09-25

Participant Flow

All 5 participants were in the \>=40 kilograms (kg) weight cohort at enrollment. Therefore, all 5 participants received the same dose of study drug for the Induction Period and the Maintenance Period as described in the study arm.

Participant milestones

Participant milestones
Measure	Eculizumab Induction Period: Participants received eculizumab (900 milligrams \[mg\]) via intravenous (IV) infusion once a week for 4 weeks. Maintenance Period: Participants received eculizumab (1200 mg) via IV infusion every 2 weeks from fifth dose (Week 4) onwards and then every 2 weeks.
Overall Study STARTED	5
Overall Study Received at Least 1 Dose of Study Drug	5
Overall Study Number of Participants Who Received Study Drug During the Induction Period	5
Overall Study Number of Participants Who Received Study Drug During the Maintenance Period	5
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Eculizumab Induction Period: Participants received eculizumab (900 milligrams \[mg\]) via intravenous (IV) infusion once a week for 4 weeks. Maintenance Period: Participants received eculizumab (1200 mg) via IV infusion every 2 weeks from fifth dose (Week 4) onwards and then every 2 weeks.
Overall Study Other than specified	3
Overall Study Withdrawal by Subject	1
Overall Study Adverse Event	1

Baseline Characteristics

A Study of the Safety and Activity of Eculizumab in Pediatric Participants With Relapsing Neuromyelitis Optica Spectrum Disorder

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Eculizumab n=5 Participants Induction Period: Participants received eculizumab (900 mg) via IV infusion once a week for 4 weeks. Maintenance Period: Participants received eculizumab (1200 mg) via IV infusion every 2 weeks from fifth dose (Week 4) onwards and then every 2 weeks.
Age, Continuous	12.0 years STANDARD_DEVIATION 4.36 • n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants
Race (NIH/OMB) White	2 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 52/53

Population: Full Analysis Set included all participants who received at least 1 dose of eculizumab. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.

ARR was calculated as the number of relapses for each participant divided by the number of years of treatment for that participant. Baseline ARR was based on 24 months prior to screening.

Outcome measures

Outcome measures
Measure	Eculizumab n=5 Participants Induction Period: Participants received eculizumab (900 mg) via IV infusion once a week for 4 weeks. Maintenance Period: Participants received eculizumab (1200 mg) via IV infusion every 2 weeks from fifth dose (Week 4) onwards and then every 2 weeks.
Change Between the Baseline Annualized Relapse Rate (ARR) and the On-Trial ARR at Week 52/53	-3.01 relapses per participant per year Standard Deviation 2.504

PRIMARY outcome

Timeframe: Baseline up to Week 52/53

Population: Full Analysis Set included all participants who received at least 1 dose of eculizumab. Note that since no participants experienced a On-trial Relapse, data was not collected for this Outcome Measure.

Time to First Relapse was defined as beginning at the time the participant's first dose of eculizumab was administered until the participant's first on-trial relapse was reported by the Investigator. Participants who did not experience an on-trial relapse were censored at the end of the study period.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Week 52/53

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. A decrease in score indicates improvement.

Outcome measures

Outcome measures
Measure	Eculizumab n=4 Participants Induction Period: Participants received eculizumab (900 mg) via IV infusion once a week for 4 weeks. Maintenance Period: Participants received eculizumab (1200 mg) via IV infusion every 2 weeks from fifth dose (Week 4) onwards and then every 2 weeks.
Change From Baseline in Expanded Disability Status Scale (EDSS) Score at Week 52/53	-0.75 score on a scale Standard Deviation 1.708

SECONDARY outcome

Timeframe: Baseline, Weeks 52/53

The HAI evaluates gait and was used to assess the time and effort used by the participant to walk 25 feet (8 meters). The scale ranged from 0 to 9, with 0 being the best score (asymptomatic; fully ambulatory with no assistance) and 9 being the worst (restricted to wheel chair; unable to transfer self independently). A decrease in score indicates improvement.

Outcome measures

Outcome measures
Measure	Eculizumab n=4 Participants Induction Period: Participants received eculizumab (900 mg) via IV infusion once a week for 4 weeks. Maintenance Period: Participants received eculizumab (1200 mg) via IV infusion every 2 weeks from fifth dose (Week 4) onwards and then every 2 weeks.
Change From Baseline in the Hauser Ambulation Index (HAI) Score at Week 52/53	0.0 score on a scale Standard Deviation 0.00

SECONDARY outcome

Timeframe: Baseline, Weeks 52/53

PedsQL included a child self-report for participants 5 to 18 years with a 23-item PedsQL Generic Core Scales report. The PedsQL Generic Core Scales report included 4 scales, physical functioning, emotional functioning, social functioning, and school functioning. Each item used a 5-point rating scale (from 0=never to 4=almost always). Items are reverse scored and linearly transformed to a 0 (almost always) -100 (never) scale. All summary/total scores were mean of specific items where higher score indicated better HRQoL.

Outcome measures

Outcome measures
Measure	Eculizumab n=4 Participants Induction Period: Participants received eculizumab (900 mg) via IV infusion once a week for 4 weeks. Maintenance Period: Participants received eculizumab (1200 mg) via IV infusion every 2 weeks from fifth dose (Week 4) onwards and then every 2 weeks.
Change From Baseline in Pediatric Quality of Life Inventory (PedsQL) Score at Week 52/53	-5.01 score on a scale Standard Deviation 10.401

SECONDARY outcome

Timeframe: Baseline, Week 52/53

The Snellen chart was used to assess VA. The Snellen chart quantifies ability to read letters of varying sizes at a fixed distance in relation to the distance at which a participant with normal vision could read the same letters. The test was performed at a standard distance, typically 6 meters or 20 feet. The Snellen chart is typically recorded as acuity ratio distance (6 meters or 20 feet), so for normal VA it would be recorded as 20/20 or 6/6. Visual acuity was summarized according to the eye with greater worsening at the end of primary treatment period (Week 52/53). Data are presented for number of participants with a shift from baseline in VA presented per the different levels of acuity ratio distance. Baseline was defined as the last available assessment prior to the first IP study drug infusion for all participants regardless of treatment group. Visual Acuity data are only reported for the categories with available data at Baseline and Week 52/53.

Outcome measures

Outcome measures
Measure	Eculizumab n=4 Participants Induction Period: Participants received eculizumab (900 mg) via IV infusion once a week for 4 weeks. Maintenance Period: Participants received eculizumab (1200 mg) via IV infusion every 2 weeks from fifth dose (Week 4) onwards and then every 2 weeks.
Number of Participants With Shift From Baseline in Visual Acuity (VA) Shift from VA 20/20-20/29 to VA 20/20-20/29	3 Participants
Number of Participants With Shift From Baseline in Visual Acuity (VA) Shift from VA 20/30-20/59 to VA 20/20-20/29	1 Participants

SECONDARY outcome

Timeframe: Baseline, Weeks 52/53

Population: Full Analysis Set included all participants who received at least 1 dose of eculizumab.

Confrontational visual fields were summarized according to the number of quadrants with deficits across both eyes. Baseline was defined as the last available assessment prior to the first IP study drug infusion for all participants regardless of treatment group.

Outcome measures

Outcome measures
Measure	Eculizumab n=3 Participants Induction Period: Participants received eculizumab (900 mg) via IV infusion once a week for 4 weeks. Maintenance Period: Participants received eculizumab (1200 mg) via IV infusion every 2 weeks from fifth dose (Week 4) onwards and then every 2 weeks.
Number of Participants With Shift From Baseline in Confrontational Visual Fields (VF) 0 to 0	2 Participants
Number of Participants With Shift From Baseline in Confrontational Visual Fields (VF) 2 to 0	1 Participants

SECONDARY outcome

Timeframe: Baseline, Weeks 52/53

Color vision was evaluated as the shift from baseline and described for participants with normal color vision at baseline in at least one eye. Participants with 13 or less correctly identified Ishihara plates were considered as having abnormal color vision, participants with 14 or more correctly identified plates were considered as having normal color vision. Baseline was defined as the last available assessment prior to the first IP study drug infusion for all participants regardless of treatment group.

Outcome measures

Outcome measures
Measure	Eculizumab n=4 Participants Induction Period: Participants received eculizumab (900 mg) via IV infusion once a week for 4 weeks. Maintenance Period: Participants received eculizumab (1200 mg) via IV infusion every 2 weeks from fifth dose (Week 4) onwards and then every 2 weeks.
Number of Participants With Shift From Baseline in Color Vision No Change from Normal	4 Participants
Number of Participants With Shift From Baseline in Color Vision Worsened from Baseline	0 Participants

SECONDARY outcome

Timeframe: Week 52

Population: Pharmacokinetic/Pharmacodynamic (PK/PD) analysis set included participants who received at least 1 dose of eculizumab and who had evaluable PK/PD data for the endpoint.

Outcome measures

Outcome measures
Measure	Eculizumab n=3 Participants Induction Period: Participants received eculizumab (900 mg) via IV infusion once a week for 4 weeks. Maintenance Period: Participants received eculizumab (1200 mg) via IV infusion every 2 weeks from fifth dose (Week 4) onwards and then every 2 weeks.
Serum Eculizumab Concentration at Week 52 Pre-dose: 5-90 Minutes	460.7 micrograms/milliliters Standard Deviation 65.04
Serum Eculizumab Concentration at Week 52 Post-dose: 60 minutes	971.3 micrograms/milliliters Standard Deviation 198.04

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: PK/PD analysis set included participants who received at least 1 dose of eculizumab and who had evaluable PK/PD data. for the endpoint. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure .

Outcome measures

Outcome measures
Measure	Eculizumab n=3 Participants Induction Period: Participants received eculizumab (900 mg) via IV infusion once a week for 4 weeks. Maintenance Period: Participants received eculizumab (1200 mg) via IV infusion every 2 weeks from fifth dose (Week 4) onwards and then every 2 weeks.
Change From Baseline in Serum Free Complement Protein 5 (C5) Concentrations at Week 52 Baseline	166.67 micrograms/milliliters Standard Deviation 50.203
Change From Baseline in Serum Free Complement Protein 5 (C5) Concentrations at Week 52 Change from Baseline at Week 52	-166.64 micrograms/milliliters Standard Deviation 50.194

Adverse Events

Eculizumab

Serious events: 2 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Eculizumab n=5 participants at risk Induction Period: Participants received eculizumab (900 mg) via IV infusion once a week for 4 weeks. Maintenance Period: Participants received eculizumab (1200 mg) via IV infusion every 2 weeks from fifth dose (Week 4) onwards and then every 2 weeks.
Investigations Liver function test increased	20.0% 1/5 • Baseline up to Week 53 Treatment emergent adverse events (TEAEs) are AEs with a start date on or after the date of the first dose of study intervention. TEAEs were analyzed for Safety Set which included all participants who received at least 1 dose of eculizumab.
Infections and infestations Encephalitis meningococcal	20.0% 1/5 • Baseline up to Week 53 Treatment emergent adverse events (TEAEs) are AEs with a start date on or after the date of the first dose of study intervention. TEAEs were analyzed for Safety Set which included all participants who received at least 1 dose of eculizumab.

Other adverse events

Other adverse events
Measure	Eculizumab n=5 participants at risk Induction Period: Participants received eculizumab (900 mg) via IV infusion once a week for 4 weeks. Maintenance Period: Participants received eculizumab (1200 mg) via IV infusion every 2 weeks from fifth dose (Week 4) onwards and then every 2 weeks.
Gastrointestinal disorders Abdominal pain lower	20.0% 1/5 • Baseline up to Week 53 Treatment emergent adverse events (TEAEs) are AEs with a start date on or after the date of the first dose of study intervention. TEAEs were analyzed for Safety Set which included all participants who received at least 1 dose of eculizumab.
Gastrointestinal disorders Bowel movement irregularity	20.0% 1/5 • Baseline up to Week 53 Treatment emergent adverse events (TEAEs) are AEs with a start date on or after the date of the first dose of study intervention. TEAEs were analyzed for Safety Set which included all participants who received at least 1 dose of eculizumab.
Gastrointestinal disorders Constipation	20.0% 1/5 • Baseline up to Week 53 Treatment emergent adverse events (TEAEs) are AEs with a start date on or after the date of the first dose of study intervention. TEAEs were analyzed for Safety Set which included all participants who received at least 1 dose of eculizumab.
Gastrointestinal disorders Dental caries	20.0% 1/5 • Baseline up to Week 53 Treatment emergent adverse events (TEAEs) are AEs with a start date on or after the date of the first dose of study intervention. TEAEs were analyzed for Safety Set which included all participants who received at least 1 dose of eculizumab.
Gastrointestinal disorders Nausea	20.0% 1/5 • Baseline up to Week 53 Treatment emergent adverse events (TEAEs) are AEs with a start date on or after the date of the first dose of study intervention. TEAEs were analyzed for Safety Set which included all participants who received at least 1 dose of eculizumab.
Gastrointestinal disorders Vomiting	20.0% 1/5 • Baseline up to Week 53 Treatment emergent adverse events (TEAEs) are AEs with a start date on or after the date of the first dose of study intervention. TEAEs were analyzed for Safety Set which included all participants who received at least 1 dose of eculizumab.
General disorders Feeling abnormal	20.0% 1/5 • Baseline up to Week 53 Treatment emergent adverse events (TEAEs) are AEs with a start date on or after the date of the first dose of study intervention. TEAEs were analyzed for Safety Set which included all participants who received at least 1 dose of eculizumab.
General disorders Pyrexia	20.0% 1/5 • Baseline up to Week 53 Treatment emergent adverse events (TEAEs) are AEs with a start date on or after the date of the first dose of study intervention. TEAEs were analyzed for Safety Set which included all participants who received at least 1 dose of eculizumab.
General disorders Vaccination site erythema	20.0% 1/5 • Baseline up to Week 53 Treatment emergent adverse events (TEAEs) are AEs with a start date on or after the date of the first dose of study intervention. TEAEs were analyzed for Safety Set which included all participants who received at least 1 dose of eculizumab.
General disorders Vaccination site pain	20.0% 1/5 • Baseline up to Week 53 Treatment emergent adverse events (TEAEs) are AEs with a start date on or after the date of the first dose of study intervention. TEAEs were analyzed for Safety Set which included all participants who received at least 1 dose of eculizumab.
Infections and infestations COVID-19	20.0% 1/5 • Baseline up to Week 53 Treatment emergent adverse events (TEAEs) are AEs with a start date on or after the date of the first dose of study intervention. TEAEs were analyzed for Safety Set which included all participants who received at least 1 dose of eculizumab.
Infections and infestations Hordeolum	20.0% 1/5 • Baseline up to Week 53 Treatment emergent adverse events (TEAEs) are AEs with a start date on or after the date of the first dose of study intervention. TEAEs were analyzed for Safety Set which included all participants who received at least 1 dose of eculizumab.
Infections and infestations Nasopharyngitis	20.0% 1/5 • Baseline up to Week 53 Treatment emergent adverse events (TEAEs) are AEs with a start date on or after the date of the first dose of study intervention. TEAEs were analyzed for Safety Set which included all participants who received at least 1 dose of eculizumab.
Infections and infestations Oral herpes	20.0% 1/5 • Baseline up to Week 53 Treatment emergent adverse events (TEAEs) are AEs with a start date on or after the date of the first dose of study intervention. TEAEs were analyzed for Safety Set which included all participants who received at least 1 dose of eculizumab.
Infections and infestations Rhinitis	20.0% 1/5 • Baseline up to Week 53 Treatment emergent adverse events (TEAEs) are AEs with a start date on or after the date of the first dose of study intervention. TEAEs were analyzed for Safety Set which included all participants who received at least 1 dose of eculizumab.
Infections and infestations Vulvovaginal candidiasis	20.0% 1/5 • Baseline up to Week 53 Treatment emergent adverse events (TEAEs) are AEs with a start date on or after the date of the first dose of study intervention. TEAEs were analyzed for Safety Set which included all participants who received at least 1 dose of eculizumab.
Musculoskeletal and connective tissue disorders Pain in extremity	40.0% 2/5 • Baseline up to Week 53 Treatment emergent adverse events (TEAEs) are AEs with a start date on or after the date of the first dose of study intervention. TEAEs were analyzed for Safety Set which included all participants who received at least 1 dose of eculizumab.
Musculoskeletal and connective tissue disorders Arthralgia	20.0% 1/5 • Baseline up to Week 53 Treatment emergent adverse events (TEAEs) are AEs with a start date on or after the date of the first dose of study intervention. TEAEs were analyzed for Safety Set which included all participants who received at least 1 dose of eculizumab.
Musculoskeletal and connective tissue disorders Back pain	20.0% 1/5 • Baseline up to Week 53 Treatment emergent adverse events (TEAEs) are AEs with a start date on or after the date of the first dose of study intervention. TEAEs were analyzed for Safety Set which included all participants who received at least 1 dose of eculizumab.
Musculoskeletal and connective tissue disorders Growing pains	20.0% 1/5 • Baseline up to Week 53 Treatment emergent adverse events (TEAEs) are AEs with a start date on or after the date of the first dose of study intervention. TEAEs were analyzed for Safety Set which included all participants who received at least 1 dose of eculizumab.
Musculoskeletal and connective tissue disorders Kyphosis	20.0% 1/5 • Baseline up to Week 53 Treatment emergent adverse events (TEAEs) are AEs with a start date on or after the date of the first dose of study intervention. TEAEs were analyzed for Safety Set which included all participants who received at least 1 dose of eculizumab.
Investigations Weight increased	20.0% 1/5 • Baseline up to Week 53 Treatment emergent adverse events (TEAEs) are AEs with a start date on or after the date of the first dose of study intervention. TEAEs were analyzed for Safety Set which included all participants who received at least 1 dose of eculizumab.
Nervous system disorders Headache	20.0% 1/5 • Baseline up to Week 53 Treatment emergent adverse events (TEAEs) are AEs with a start date on or after the date of the first dose of study intervention. TEAEs were analyzed for Safety Set which included all participants who received at least 1 dose of eculizumab.
Nervous system disorders Hypoaesthesia	20.0% 1/5 • Baseline up to Week 53 Treatment emergent adverse events (TEAEs) are AEs with a start date on or after the date of the first dose of study intervention. TEAEs were analyzed for Safety Set which included all participants who received at least 1 dose of eculizumab.
Eye disorders Chalazion	20.0% 1/5 • Baseline up to Week 53 Treatment emergent adverse events (TEAEs) are AEs with a start date on or after the date of the first dose of study intervention. TEAEs were analyzed for Safety Set which included all participants who received at least 1 dose of eculizumab.
Eye disorders Dry eye	20.0% 1/5 • Baseline up to Week 53 Treatment emergent adverse events (TEAEs) are AEs with a start date on or after the date of the first dose of study intervention. TEAEs were analyzed for Safety Set which included all participants who received at least 1 dose of eculizumab.
Hepatobiliary disorders Hepatic steatosis	20.0% 1/5 • Baseline up to Week 53 Treatment emergent adverse events (TEAEs) are AEs with a start date on or after the date of the first dose of study intervention. TEAEs were analyzed for Safety Set which included all participants who received at least 1 dose of eculizumab.
Injury, poisoning and procedural complications Post vaccination fever	20.0% 1/5 • Baseline up to Week 53 Treatment emergent adverse events (TEAEs) are AEs with a start date on or after the date of the first dose of study intervention. TEAEs were analyzed for Safety Set which included all participants who received at least 1 dose of eculizumab.
Metabolism and nutrition disorders Hypercalcaemia	20.0% 1/5 • Baseline up to Week 53 Treatment emergent adverse events (TEAEs) are AEs with a start date on or after the date of the first dose of study intervention. TEAEs were analyzed for Safety Set which included all participants who received at least 1 dose of eculizumab.
Metabolism and nutrition disorders Lactic acidosis	20.0% 1/5 • Baseline up to Week 53 Treatment emergent adverse events (TEAEs) are AEs with a start date on or after the date of the first dose of study intervention. TEAEs were analyzed for Safety Set which included all participants who received at least 1 dose of eculizumab.
Psychiatric disorders Impulse-control disorder	20.0% 1/5 • Baseline up to Week 53 Treatment emergent adverse events (TEAEs) are AEs with a start date on or after the date of the first dose of study intervention. TEAEs were analyzed for Safety Set which included all participants who received at least 1 dose of eculizumab.
Renal and urinary disorders Urinary incontinence	20.0% 1/5 • Baseline up to Week 53 Treatment emergent adverse events (TEAEs) are AEs with a start date on or after the date of the first dose of study intervention. TEAEs were analyzed for Safety Set which included all participants who received at least 1 dose of eculizumab.
Reproductive system and breast disorders Amenorrhoea	25.0% 1/4 • Baseline up to Week 53 Treatment emergent adverse events (TEAEs) are AEs with a start date on or after the date of the first dose of study intervention. TEAEs were analyzed for Safety Set which included all participants who received at least 1 dose of eculizumab.
Respiratory, thoracic and mediastinal disorders Epistaxis	20.0% 1/5 • Baseline up to Week 53 Treatment emergent adverse events (TEAEs) are AEs with a start date on or after the date of the first dose of study intervention. TEAEs were analyzed for Safety Set which included all participants who received at least 1 dose of eculizumab.
Skin and subcutaneous tissue disorders Erythema	20.0% 1/5 • Baseline up to Week 53 Treatment emergent adverse events (TEAEs) are AEs with a start date on or after the date of the first dose of study intervention. TEAEs were analyzed for Safety Set which included all participants who received at least 1 dose of eculizumab.

Additional Information

Alexion Pharmaceuticals Inc.

Phone: 855-752-2356

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place