Clinical trial NCT06510283: Efficacy and Safety of Taitacept in Treatment of Refractory or Recurrent Anti-NMDAR/anti-LGI1 Encephalitis
Official title: Efficacy and Safety of Taitacept in Treatment of Refractory or Recurrent Anti-NMDAR/anti-LGI1 Encephalitis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Anti-N-Methyl-D-Aspartate Receptor Encephalitis
Lead sponsor: Beijing Tongren Hospital
Sponsor class: OTHER
First posted: 2024-07-19
Enrollment: 10
Sex: ALL
Minimum age (years): 14
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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).

Primary outcomes:
measure: the change of mRS score
timeFrame: from baseline at week 24
Secondary outcomes:
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Tongren Hospital,Capital Medical University
state: Beijing
Study officials:
affiliation: Beijing Tong Ren Hospital
name: Jiawei Wang
role: STUDY_DIRECTOR
References: