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Pilot study of Rituximab for the treatment of fatigue in PBC

Phase 1
Conditions
Severe fatigue in Primary Biliary Cirrhosis
MedDRA version: 18.0 Level: PT Classification code 10004661 Term: Biliary cirrhosis primary System Organ Class: 10019805 - Hepatobiliary disorders
Therapeutic area: Diseases [C] - Digestive System Diseases [C06]
Registration Number
EUCTR2012-000145-12-GB
Lead Sponsor
The Newcastle upon Tyne Hospitals NHS Foundation Trust
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
ot Recruiting
Sex
Not specified
Target Recruitment
57
Inclusion Criteria

• Age 18 years or over
• 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
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 29
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 29

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 trial entry
• Vaccination within 4 weeks of trial entry, patients requiring seasonal flu or travel vaccines will be required to wait a minimum of 4 weeks post vaccination to enroll in the trial
• 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 trial
• 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 trial
•Any contraindication to Rituximab therapy not covered by other exclusions

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Secondary Outcome Measures
NameTimeMethod
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