Efficacy and Safety of Taitacept in Treatment of Refractory or Recurrent Anti-NMDAR/anti-LGI1 Encephalitis

The main objective is to explore the efficacy and safety of Telitacicept in the treatment of refractory/recurrent anti-NMDAR and anti-LGI1 encephalitis.

Through this prospective, single-center, open-label clinical trial, we aim to investigate the effectiveness and safety of Telitacicept in refractory/recurrent anti-NMDAR and anti-LGI1 encephalitis by add-on therapy of Telitacicept combined with traditional treatment.

Study Overview

• Status: Recruiting
• Conditions: Anti-N-Methyl-D-Aspartate Receptor Encephalitis
• Intervention / Treatment: Drug: Taitacept

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jiawei Wang, PHD; Phone Number: 010-58266091; Email: pengyujing1206@163.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100730
      • Recruiting
      • Beijing Tongren Hospital,Capital Medical University
      • Contact: Jiawei Wang, doctor; Phone Number: 18811612263; Email: pengyujing1206@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥14 years old, male or female;
2. Symptoms of autoimmune encephalitis (AE) ≤ 9 months prior to enrollment;

3. Diagnosed as autoimmune encephalitis, diagnostic criteria as follows:

   1. Rapid onset (<3 months) of at least four of the following six major symptoms:

      • Abnormal (mental) behavior or cognitive dysfunction
      • Speech dysfunction (verbal urgency, hypospeech, mutism)
      • Seizures
      • Movement disorders, dyskinesias, or postural rigidity/abnormalities
      • Decreased level of consciousness
      • Autonomic dysfunction or central hypoventilation in the presence of one or more of the six major symptoms;
   2. Positive anti-NMDAR (GluN1) IgG antibody detected in CSF or positive serum and/or cerebrospinal fluid LGI1 antibody; c．Reasonable exclusion of other etiologies and other well-defined encephalitis syndromes (e.g., Bickerstaff brainstem encephalitis, acute disseminated encephalomyelitis, Hashimoto encephalopathy, primary CNS vasculitis, Rasmussen encephalitis);
4. Refractory AE: ineffective treatment with steroids and rituximab or other immunosuppressants, post-treatment mRS score≥2 (stable for at least 24 hours）;Recurrent AE: at least 2 months after 1st or 2nd line treatment, new symptoms or worsening of existing symptoms (mRS increase>1); 5）Doses of steroids and other immunosuppressants (e.g. azathioprine, mycophenolate mofetil, cyclophosphamide) should be stabilised for 4 weeks prior to enrolment; 6）Ability to obtain patient or proxy consent; 7）Women of childbearing potential should use effective contraception during treatment or avoid heterosexual intercourse for at least 3 months after the last dose of talitacicept;

Exclusion Criteria:

1. History of other autoimmunity such as SLE, RA, SS. Patients with hyperthyroidism and hypothyroidism cannot be excluded;

2. Abnormal laboratory indicators, including but not limited to the following indicators:

   White blood cell count<3×10^9 /L Neutrophil count<1.5×10^9 /L Hemoglobin<85g/L Blood platelet count<80×10^9 /L Serum creatinine>1.5×ULN TBil(total bilirubin) >1.5×ULN ALT>3× ULN AST>3× ULN Alkaline phosphatase>2× ULN Creatine kinase>5× ULN

3. Evidence of active infection such as shingles, HIV or active tuberculosis, etc.

4. Currently have active hepatitis or have severe liver disease and a history of it.

   • Patiens with abnormal Hepatitis B test as follows should be excluded: HbsAg positive; HbsAg negative but HbcAb positive, and HBV-DNA positive. Whereas patients with HbsAg negative but HbcAb positive, and HBV-DNA negative can be included.
   • Exclude patients who are positive for hepatitis C antibodies ;
5. Uncontrolled diabetes mellitus: Glycosylated hemoglobin>9.0% or fasting blood glucose≥11.1mmol/L;
6. Received any live vaccine within 3 months prior to enrollment or planned to receive any vaccine during the study;
7. Received rituximab or other biological therapies within 1 month prior to enrollment;
8. Malignancy;
9. Allergic to human biological products;
10. Participated in any clinical trial within 28 days prior to enrollment or within 5 times the half-life of the investigational drug participating in the clinical trial
11. Patients who plan to have children during the trial, or who are pregnant or breastfeeding;
12. Alcohol or drug abuse/addiction is known to have an impact on compliance with trial requirements;
13. Patients who are deemed unsuitable for the trial by the investigator (e.g., those with severe mental disorders).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Taitacept treatment group; Telitacicept will be subcutaneously injected at a dose of 240mg per week, lasting for at least 24 weeks.	Drug: Taitacept; Telitacicept will be subcutaneously injected at a dose of 240mg per week, lasting for at least 24 weeks.; Other Names: No other Intervention Names

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the change of mRS score	Refractory encephalitis: rate of patients with mRS score <2 or mRS score improvement of ≥2 points from baseline at week 24; Recurrent encephalitis: proportion of patients with no recurrence and [mRS score <2 or mRS score improvement of ≥2 points from baseline at week 24. mRS score vary from 0-6 score and higher scores mean a worse outcome.	from baseline at week 24

Collaborators and Investigators

• Sponsor: Beijing Tongren Hospital
• Investigators: Study Director: Jiawei Wang, Beijing Tong Ren Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2024
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2028

Study Registration Dates

• First Submitted: July 15, 2024
• First Submitted That Met QC Criteria: July 15, 2024
• First Posted (Actual): July 19, 2024

Study Record Updates

• Last Update Posted (Estimated): November 20, 2024
• Last Update Submitted That Met QC Criteria: November 18, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neuroinflammatory Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Neoplasms; Autoimmune Diseases; Immune System Diseases; Autoimmune Diseases of the Nervous System; Neurodegenerative Diseases; Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Paraneoplastic Syndromes; Encephalitis; Anti-N-Methyl-D-Aspartate Receptor Encephalitis
• Other Study ID Numbers: TREC2024-KY061

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No