Primary Biliary Cirrhosis: Investigating A New Treatment Option using NI-0801, a fully human anti-CXCL10 monoclonal antibody.

• Register: EUCTR
• Last refreshed on: 5 November 2012
• Main ID: EUCTR2011-001326-26-GB
• Date of registration: 24/03/2011
• Prospective Registration: Yes
• Primary sponsor: NovImmune S.A.
• Public title: Primary Biliary Cirrhosis: Investigating A New Treatment Option using NI-0801, a fully human anti-CXCL10 monoclonal antibody.
• Scientific title: PIANO. Primary Biliary Cirrhosis: Investigating A New Treatment Option using NI-0801, a fully human anti-CXCL10 monoclonal antibody. An open label single arm study to investigate the safety and efficacy of multiple administrations of NI-0801, a fully human anti-CXCL10 monoclonal antibody in primary biliary cirrhosis patients with an incomplete response to ursodeoxycholic acid. - PIANO
• Date of first enrolment: 27/05/2011
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-001326-26
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no

Countries of recruitment

Italy, United Kingdom

Key inclusion & exclusion 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:
1. Screening bilirubin > 2.9 mg/dL (50 µmol/L)
2. Screening creatinine clearance < 80 ml/min
3. History or presence of hepatic decompensation
4. History or presence of other concomitant liver diseases including hepatitis due to hepatitis B or C virus (HCV, HBV), primary sclerosing cholangitis (PSC), alcoholic liver disease, definite autoimmune liver disease (AIH) and biopsy proven nonalcoholic steatohepatitis (NASH)
5. Positive serology result for Human Immunodeficiency Virus (HIV), Hepatitis B or C
6. Average alcohol ingestion >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


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Primary biliary cirrhosis
MedDRA version: 14.1 Level: LLT Classification code 10036680 Term: Primary biliary cirrhosis System Organ Class: 10019805 - Hepatobiliary disorders

Intervention(s)

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
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Primary Outcome(s)

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 Outcome(s)

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

Secondary ID(s)

NI-0801-03