Primary biliary cirrhosis MedDRA version: 14.1 Level: LLT Classification code 10036680 Term: Primary biliary cirrhosis System Organ Class: 10019805 - Hepatobiliary disorders
Conditions
Interventions
Product Code: NI-0801
Pharmaceutical Form: Concentrate for solution for infusion
Current Sponsor code: NI-0801
Other descriptive name: fully human monoclonal antibody directed against CXCL10
Concentra
Sponsors
NovImmune S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female, 18 years or older 2. Proven PBC, as demonstrated by the presence of at least 2 of the following 3 diagnostic factors: - History of increased ALP levels for at least 6 months - Positive serum AMA titer (>1:40) - Liver biopsy consistent with PBC 3. Incomplete response to UDCA defined as failure to normalise ALP levels or to reduce ALP levels by more than 40% after 1 year of therapy with UDCA according to the local recommended dose. 4. Stable dose of UDCA for at least 6 months prior to screening 5. Screening ALP > 1.5 ULN 6. Screening ALT or AST > 1.5 ULN 7. Female patients must be postmenopausal, surgically sterile, or willing to use 2 methods of effective contraception with all sexual partners until 3 months after having received the last dose of study medication 8. Male patients who agree to take the appropriate precautions to avoid fathering a child until 3 months after having received the last dose of study medication 9. Have given written informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 35 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: 1. Screening bilirubin > 2.9 mg/dL (50 µmol/L) 2. Screening creatinine clearance 21 units/week (male) / >14 units/week (female) 7. Have received any immunosuppressants, steroids or peroxisome proliferator activation receptor (PPAR) activators at any time during the 3 months prior to screening for the study 8. Known or previous diagnosis of malignancy 9. Presence of any active infection 10. Presence or history of multiple allergic reactions to drugs 11. Previous history of active TB within 12 months of screening 12. Pregnant or breastfeeding women 13. Have received or plan to receive any vaccines within 6 weeks prior to receiving study drug and throughout the study period
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the efficacy of multiple doses of NI 0801 on hepatic function ;Secondary Objective: To evaluate the safety and tolerability of multiple doses of NI-0801 in primary biliary cirrhosis patients To characterize the pharmacokinetic and pharmacodynamic profile of multiple doses of NI 0801 To assess immunogenicity of NI 0801;Primary end point(s): Change in liver enzyme measurements from baseline to Week 12 (SD85);Timepoint(s) of evaluation of this end point: Week 12 (SD85) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): PBC-related exploratory assessments • Biochemical markers of liver function • Mayo risk score (MRS) • Liver stiffness measurement (LSM) with Transient Elastography (Fibroscan™) • Enhanced Liver Fibrosis (ELF) test • Quality-of-Life assessment: PBC-40 Pharmacokinetic characterisation Pharmacodynamic measurements • The evolution over time of total circulating CXCL10 levels will be measured Extent of the NI 0801 inhibition on CXCL10 chemotactic activity by in vitro chemotaxis • Serum cytokines and chemokines • FACS analysis for the quantification of leukocytes and subsets and CXCR3 expression on these subsets Safety and tolerability • All emerging AEs • The number of subjects withdrawing from the study for safety related reasons • Vital signs and any changes revealed by medical examination. • Laboratory abnormalities in Safety Hematology parameters, Safety Blood Chemistry parameters and Urinalysis parameters Immunogenicity • The presence of anti-drug antibodies ;Timepoint(s) of evaluation of this end point: ELF, Fibroscan, PBC-40: SD1, SD85, W18 PK, blood samples: SD1, SD5, SD15, SD29, SD43, SD57, SD71, SD75, SD85, W18, W24 Chemokines/cytokines: SD1, SD5, SD15, SD29, SD43, SD57, SD71, SD75, SD85, W18, W24 FACS: SD1, SD85 Immunogenicity: SD1, SD15, SD29, SD43, SD57, SD71, W24 Vital signs, hematology and biochemistry blood samples, AEs recording & concomittant medications: SD1, SD5, SD15, SD29, SD43, SD57, SD71, SD75, SD85, W18, W24 | — |
Countries
Italy, United Kingdom
Outcome results
None listed