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 Patient should be on incomplete response to UDCA MedDRA version: 14.1 Level: SOC Classification code 10021428 Term: Immune system disorders System Organ Class: 10021428 - Immune system disorders MedDRA version: 14.1 Level: SOC Classification code 10019805 Term: Hepato
Conditions
Interventions
Product Name: NI-0801
Product Code: NI-0801
Pharmaceutical Form: Concentrate for solution for infusion
Current Sponsor code: NI-0801
Concentration unit: mg/ml milligram(s)/millilitre
Concentration typ
Sponsors
NOVIMMUNE BV
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 10. Patients must be able to adhere to the study visits and protocol requirements 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 80 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Screening bilirubin > 2.9 mg/dL (50 µmol/L) • Screening creatinine clearance < 80 ml/min • History or presence of hepatic decompensation (e.g., esophageal variceal bleeding, hepatic encephalopathy, or ascites) • Positive serology result for Human Immunodeficiency Virus (HIV), Hepatitis B or C • Known or previous diagnosis of malignancy • Presence of any active infection • Previous history of active TB within 12 months of screening
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 PBC patients •To characterize the pharmacokinetic and pharmacodynamic profile of multiple doses 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 relatedreasons • 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
Contacts
Public ContactCentro Malattie Autoimmuni Fegato
IRCCS Istituto Clinico Humanitas
Outcome results
None listed