Ofatumumab in AQP4-IgG Seropositive NMOSD

Neuromyelitis Optica Spectrum Disorder Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05504694
• Other study ID #: K202206-13
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: June 28, 2022
• Est. completion date: December 2024

Study information

• Verified date: August 2022
• Source: Tang-Du Hospital
• Contact: Jun Guo, M.D.
• Phone: 86-29-8477 8844
• Email: guojun_81[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 5
• Est. completion date: December 2024
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Neuromyelitis Optica
• Neuromyelitis Optica Spectrum Disorder

Intervention

Drug:
• Ofatumumab
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.

Locations

Country	Name	City	State
China	Tangdu Hospital	Xi'an	Shaanxi

Sponsors (2)

Lead Sponsor	Collaborator
Tang-Du Hospital	Henan Provincial People's Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	baseline, 12 months
Secondary	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.	baseline, 3 months, 6 months, 9 months, 12 months
Secondary	Change from baseline in lesion burden on MRI T2-weighted images	MRI is conducted to measure the lesion burden on T2-weighted images.	baseline, 6 months, 12 months
Secondary	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.	baseline, 6 months, 12 months
Secondary	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.	baseline, 1 week, 2 weeks, 1 month, 3 months, 6 months, 9 months, 12 months
Secondary	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-1ß, IL-2, IL-4, etc.	baseline, 1 week, 2 weeks, 1 month, 3 months, 6 months, 9 months, 12 months
Secondary	Biochemical indicators monitoring	Blood routine test, liver and kidney function, immunoglobulins, complement, and serum AQP4-IgG titer.	baseline, 1 month, 3 months, 6 months, 9 months, 12 months
Secondary	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.	baseline, 1 month, 3 months, 6 months, 9 months, 12 months
Secondary	Adverse events	Ofatumumab-related adverse events (AEs) are evaluated and the rate of AEs is recorded.	1 week, 2 weeks, 1 month, 3 months, 6 months, 9 months, 12 months