B-Cell Depleting Therapy (Rituximab) as a Treatment for Fatigue in Primary Biliary Cirrhosis (RITPBC)
Fatigue, Primary Biliary Cirrhosis
About this trial
This is an interventional treatment trial for Fatigue focused on measuring Fatigue, Primary Biliary Cirrhosis, Rituximab, PBC-40
Eligibility Criteria
Inclusion Criteria:
- age ≥ 18 years
- patient has capacity and provided written informed consent for participation in the study prior to any study specific procedures
- moderate or severe fatigue as assessed using previously designated cut-offs of the PBC-40 fatigue domain (i.e. fatigue domain score >33)
- presence of AMA (anti-PDH antibody) at a titre of >1:40
- adequate haematological function Hb >9g/L, Absolute neutrophil count >1.5x109/L, platelet count > 50x109/L
- bilirubin ≤ 50 μmol
- INR ≤ 1.5
- Child-Pugh score < 7
- ECOG performance status < 2
- adequate renal function; Cockroft and Gault estimation > 40ml/min
women of childbearing potential should have a negative pregnancy test prior to study entry AND be using an adequate contraception method, which must be continued for 12 months after completion of treatment. Acceptable forms of effective contraception include:
- established use of oral, injected or implanted hormonal methods of contraception
- placement of an intrauterine device (IUD) or intrauterine system (IUS)
- barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository
- male sterilisation (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate)
- true abstinence: when this is in line with the preferred and usual lifestyle of the subject
Exclusion Criteria:
- advanced or decompensated disease (variceal bleed, hepatic encephalopathy or ascites)
- history or presence of other concomitant liver diseases (including hepatitis due to hepatitis B (surface antigen positive or core antibody positive) or C or evidence of chronic viraemia on baseline screening), primary sclerosing cholangitis or biopsy proven non-alcoholic steatohepatitis)
- average alcohol ingestion >21 units/week (male) or >14 units / week (female)
- chronic sepsis or intercurrent condition likely to predispose to chronic sepsis during the study
- previous treatment with B-cell depleting therapy
- previous history of aberrant response or intolerance to immunological agents
- presence of significant untreated intercurrent medical condition itself associated with fatigue
- presence of significant risk of depressive illness (HADS score indicating caseness)
- current statin therapy or statin use within 3 months of enrolment
- ongoing participation in other clinical trials or exposure to any investigational agent 4 weeks prior to baseline or within < 5 half lives of the investigational drug
- major surgery within 4 weeks of study entry
- vaccination within 4 weeks of study entry; patients requiring seasonal flu or travel vaccines will be required to wait a minimum of 4 weeks post vaccination to enrol in the study
- pregnant or lactating women
- psychiatric or other disorder likely to impact on informed consent
- patient is unable and/or unwilling to comply with treatment and study instructions
- any other medical condition that, in the opinion of the investigator would interfere with safe completion of the study
- hypersensitivity to the active substance (Rituximab) or to any of the excipients (sodium citrate, polysorbate 80, sodium chloride, sodium hydroxide, hydrochloric acid, water (for infusion)) or to murine proteins
- active, severe infections (e.g. tuberculosis, sepsis or opportunistic infections)
- known HIV infection
- clinical history of latent TB infection unless the patient has completed adequate antibiotic prophylaxis
- AST/ALT 4 x upper limit of normal
- severe immune-compromised state
- severe heart failure (NYHA Class IV) or severe uncontrolled cardiac disease
- malignancy (other than basal cell carcinoma) within the last 10 years
- demyelinating disease
- previous participation in this study
- any contraindication to Rituximab therapy not covered by other exclusions
Sites / Locations
- Newcastle Clinical Trials Unit
Arms of the Study
Arm 1
Arm 2
Active Comparator
Placebo Comparator
Rituximab infusion
Placebo infusion
Participants will be randomised to Rituximab therapy (1000 mg IV on days 1 and 15) or placebo (0.9% Sodium Chloride 250mls) control.
Participants will be randomised to Rituximab therapy (1000 mg IV on days 1 and 15) or placebo (0.9% Sodium Chloride 250mls) control.