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Ofatumumab in AQP4-IgG Seropositive NMOSD

Primary Purpose

Neuromyelitis Optica Spectrum Disorder

Status

Recruiting

Phase

Phase 1

Locations

China

Study Type

Interventional

Intervention

Ofatumumab

About this trial

This is an interventional treatment trial for Neuromyelitis Optica Spectrum Disorder focused on measuring Neuromyelitis Optica Spectrum Disorder, Aquaporin 4, Ofatumumab

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Diagnosis of NMOSD according to the 2015 International Panel Diagnostic Criteria for NMOSD with AQP4-IgG.
Clinical evidence of at least 2 relapses (including first attack) in past 24 months with at least 1 relapse occurring in the preceding 12 months.
Adults aged ≥18 years old.
Expanded disability status scale (EDSS) score between 0 and 7.5 (inclusive).
Provision of written informed consent to participate in this study.
Only oral corticosteroids were permitted at screening (≤10mg equivalent per day), which should be terminated within one month.
Effective contraception was used for female patients with fertility during the treatment or at least 3 months after stopping medication.

Exclusion Criteria:

Progressive neurological deterioration unrelated to relapses of NMOSD, or presence of neurological findings suspected with PML.
Pregnant or breastfeeding patients and those with family planning during the study period.
Patients participating in any other clinical therapeutic study at the screening or within 30 days of screening.
Patients with splenectomy or history of no spleen, and those with planned surgery (excluding minor surgery) during the study period.
Presence of uncontrolled severe concurrent diseases; long-term glucocorticoids or immunosuppressants use due to other autoimmune diseases, or presence of other chronic diseases that cannot receiving immunosuppression.
Active infection at within 4 weeks before baseline.
Positive for HBV or HCV.
Evidence of latent or active tuberculosis (TB).
Have received any live or live-attenuated vaccine within 6 weeks before baseline.
History of malignancy in past 5 years, including solid tumor, malignant hematopathy and carcinoma in situ.
History of severe allergic reactions to biological agents.
Inability to provide written informed consent.

Sites / Locations

Tangdu HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Ofatumumab

Arm Description

Outcomes

Primary Outcome Measures

Change from baseline in annual relapse rate (ARR) at last follow-up visit

Pre-treatment ARR was determined at baseline by the total number of attacks divided by disease course from onset to baseline; post-treatment ARR is determined at 12 months after treatment by the number of relapses divided by 12 months.

Secondary Outcome Measures

Change from baseline in Expanded Disability Status Scale (EDSS) score

Patients are followed up and EDSS score is determined. In general, the minimum and maximum scores of EDSS are 0 and 10, respectively, with higher scores meaning a worse outcome.

Change from baseline in lesion burden on MRI T2-weighted images

MRI is conducted to measure the lesion burden on T2-weighted images.

Change from baseline in optic coherence tomography (OCT) measures

OCT is done to measure peripapillary retinal nerve fiber layer (RNFL) thickness, macular ganglion cell-inner plexiform layer (GCIPL) thickness, and macular inner nuclear layer (INL) thickness.

Change from baseline in the frequencies of circulating B cell subsets

Circulating B cell monitoring is conducted to evaluate the effectiveness of B-cell-depletion therapy. FACS is used to measure the frequencies of CD19+ B cells, CD19+CD27+ memory B cells, and CD19+CD38+CD27+ plasmablasts.

Change from baseline in immune landscape

The dynamic changes of immune cells and cytokines are monitored, such as Th1 cells, Th2 cells, Th17 cells, NK cells, IL-1β, IL-2, IL-4, etc.

Biochemical indicators monitoring

Blood routine test, liver and kidney function, immunoglobulins, complement, and serum AQP4-IgG titer.

Assessment of functional questionnaire

SF-36, Functional Assessment of Chronic Illness Therapy (FACIT), EuroQol Health State (EQ-5D), Visual Analogue Pain Scale (VAPS), Timed 25-foot Walk Test, etc.

Adverse events

Ofatumumab-related adverse events (AEs) are evaluated and the rate of AEs is recorded.

Full Information

NCT ID

NCT05504694

First Posted

August 16, 2022

Last Updated

August 16, 2022

Sponsor

Tang-Du Hospital

Collaborators

Henan Provincial People's Hospital

1. Study Identification

Unique Protocol Identification Number

NCT05504694

Brief Title

Ofatumumab in AQP4-IgG Seropositive NMOSD

Official Title

Efficacy and Safety of Ofatumumab in AQP4-IgG Seropositive NMOSD: an Open-label, Single-arm, Multicentre Prospective Pilot Study

Study Type

Interventional

2. Study Status

Record Verification Date

August 2022

Overall Recruitment Status

Recruiting

Study Start Date

June 28, 2022 (Actual)

Primary Completion Date

June 2024 (Anticipated)

Study Completion Date

December 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Tang-Du Hospital

Collaborators

Henan Provincial People's Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief Summary

This is an open-label, single-arm, multicentre prospective pilot study to assess the efficacy and safety of ofatumumab in patients with AQP4-IgG seropositive neuromyelitis optica spectrum disorder (NMOSD) in China.

Detailed Description

Neuromyelitis optica spectrum disorder (NMOSD) is a rare but severe demyelinating disorder that affects mainly adult patients. It is associated with a pathological B cell-mediated humoral immune response against the aquaporin-4 (AQP4) water channel. Monoclonal antibodies against CD20 have been shown to be effective for prevention of relapses in patients with NMOSD, and therefore been recommended as first-line therapy for this disorder. Ofatumumab (OFA), a fully humanized anti-CD20 monoclonal antibody, has been approved for multiple sclerosis treatment. However, prospective multicenter studies are needed to determine the efficacy and safety of ofatumumab in treating NMOSD.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Neuromyelitis Optica Spectrum Disorder

Keywords

Neuromyelitis Optica Spectrum Disorder, Aquaporin 4, Ofatumumab

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

5 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Ofatumumab

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Ofatumumab

Other Intervention Name(s)

Arzerra

Intervention Description

The enrolled patients will receive ofatumumab (20 mg/0.4 ml) subcutaneously administered at baseline, Day 7, Day 14 and monthly thereafter. Patients will receive ofatumumab therapy for a total of 48 weeks. The first 4 infusions will be administered at study center site; subsequent infusions will be given in the patient's home with a nurse online interview to administer the infusion.

Primary Outcome Measure Information:

Title

Change from baseline in annual relapse rate (ARR) at last follow-up visit

Description

Time Frame

baseline, 12 months

Secondary Outcome Measure Information:

Title

Change from baseline in Expanded Disability Status Scale (EDSS) score

Description

Patients are followed up and EDSS score is determined. In general, the minimum and maximum scores of EDSS are 0 and 10, respectively, with higher scores meaning a worse outcome.

Time Frame

baseline, 3 months, 6 months, 9 months, 12 months

Title

Change from baseline in lesion burden on MRI T2-weighted images

Description

MRI is conducted to measure the lesion burden on T2-weighted images.

Time Frame

baseline, 6 months, 12 months

Title

Change from baseline in optic coherence tomography (OCT) measures

Description

OCT is done to measure peripapillary retinal nerve fiber layer (RNFL) thickness, macular ganglion cell-inner plexiform layer (GCIPL) thickness, and macular inner nuclear layer (INL) thickness.

Time Frame

baseline, 6 months, 12 months

Title

Change from baseline in the frequencies of circulating B cell subsets

Description

Time Frame

baseline, 1 week, 2 weeks, 1 month, 3 months, 6 months, 9 months, 12 months

Title

Change from baseline in immune landscape

Description

The dynamic changes of immune cells and cytokines are monitored, such as Th1 cells, Th2 cells, Th17 cells, NK cells, IL-1β, IL-2, IL-4, etc.

Time Frame

baseline, 1 week, 2 weeks, 1 month, 3 months, 6 months, 9 months, 12 months

Title

Biochemical indicators monitoring

Description

Blood routine test, liver and kidney function, immunoglobulins, complement, and serum AQP4-IgG titer.

Time Frame

baseline, 1 month, 3 months, 6 months, 9 months, 12 months

Title

Assessment of functional questionnaire

Description

SF-36, Functional Assessment of Chronic Illness Therapy (FACIT), EuroQol Health State (EQ-5D), Visual Analogue Pain Scale (VAPS), Timed 25-foot Walk Test, etc.

Time Frame

baseline, 1 month, 3 months, 6 months, 9 months, 12 months

Title

Adverse events

Description

Ofatumumab-related adverse events (AEs) are evaluated and the rate of AEs is recorded.

Time Frame

1 week, 2 weeks, 1 month, 3 months, 6 months, 9 months, 12 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Diagnosis of NMOSD according to the 2015 International Panel Diagnostic Criteria for NMOSD with AQP4-IgG. Clinical evidence of at least 2 relapses (including first attack) in past 24 months with at least 1 relapse occurring in the preceding 12 months. Adults aged ≥18 years old. Expanded disability status scale (EDSS) score between 0 and 7.5 (inclusive). Provision of written informed consent to participate in this study. Only oral corticosteroids were permitted at screening (≤10mg equivalent per day), which should be terminated within one month. Effective contraception was used for female patients with fertility during the treatment or at least 3 months after stopping medication. Exclusion Criteria: Progressive neurological deterioration unrelated to relapses of NMOSD, or presence of neurological findings suspected with PML. Pregnant or breastfeeding patients and those with family planning during the study period. Patients participating in any other clinical therapeutic study at the screening or within 30 days of screening. Patients with splenectomy or history of no spleen, and those with planned surgery (excluding minor surgery) during the study period. Presence of uncontrolled severe concurrent diseases; long-term glucocorticoids or immunosuppressants use due to other autoimmune diseases, or presence of other chronic diseases that cannot receiving immunosuppression. Active infection at within 4 weeks before baseline. Positive for HBV or HCV. Evidence of latent or active tuberculosis (TB). Have received any live or live-attenuated vaccine within 6 weeks before baseline. History of malignancy in past 5 years, including solid tumor, malignant hematopathy and carcinoma in situ. History of severe allergic reactions to biological agents. Inability to provide written informed consent.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Jun Guo, M.D.

Phone

86-29-8477 8844

guojun_81@163.com

First Name & Middle Initial & Last Name or Official Title & Degree

Yan Jia, M.S.

Phone

86-29-8471 7483

neurologist_jiayan@163.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jun Guo, M.D.

Organizational Affiliation

Tang-Du Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Tangdu Hospital

City

Xi'an

State/Province

Shaanxi

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Jun Guo, M.D.

Phone

86-29-8477 8844

guojun_81@163.com

First Name & Middle Initial & Last Name & Degree

Yan Jia, M.S.

Phone

86-29-8471 7483

neurologist_jiayan@163.com

First Name & Middle Initial & Last Name & Degree

Jun Guo, M.D.

12. IPD Sharing Statement

Learn more about this trial

Ofatumumab in AQP4-IgG Seropositive NMOSD

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