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

Korábbi kezelés

• Received any live vaccine within 3 months prior to enrollment or planned to receive any vaccine during the study;
• Received rituximab or other biological therapies within 1 month prior to enrollment;
• 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
• Alcohol or drug abuse/addiction is known to have an impact on compliance with trial requirements;

Más betegség

• History of other autoimmunity such as SLE, RA, SS. Patients with hyperthyroidism and hypothyroidism cannot be excluded;
• Evidence of active infection such as shingles, HIV or active tuberculosis, etc.
• 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 ;
• Malignancy;
• Allergic to human biological products;
• Patients who are deemed unsuitable for the trial by the investigator (e.g., those with severe mental disorders).

Laborértékek

• 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
• Uncontrolled diabetes mellitus: Glycosylated hemoglobin>9.0% or fasting blood glucose≥11.1mmol/L;

Egyéb

• Patients who plan to have children during the trial, or who are pregnant or breastfeeding;

• Age ≥14 years old, male or female;
• Symptoms of autoimmune encephalitis (AE) ≤ 9 months prior to enrollment;
• Diagnosed as autoimmune encephalitis, diagnostic criteria as follows:
  • 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;
  • 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);
• 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;