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

• Register: EUCTR
• Last refreshed on: 29 October 2012
• Main ID: EUCTR2011-001326-26-IT
• Date of registration: 19/01/2012
• Prospective Registration: No
• Primary sponsor: NOVIMMUNE BV
• Public title: Primary Biliary Cirrhosis: Investigating A New Treatment Option using NI 0801, a fully human anti-CXCL10 monoclonal antibody.
• Scientific title: 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: 21/06/2011
• Target sample size: 40
• 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: Placebo: Other: Number of treatment arms in the trial: 1

Countries of recruitment

Italy

Contacts

• Name: Centro Malattie Autoimmuni Fegato
• Affiliation: IRCCS Istituto Clinico Humanitas

• Name: Centro Malattie Autoimmuni Fegato
• Affiliation: IRCCS Istituto Clinico Humanitas

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 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:
• 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


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

Health Condition(s) or Problem(s) studied

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

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: Hepatobiliary disorders System Organ Class: 10019805 - Hepatobiliary disorders

Intervention(s)

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 type: equal
Concentration number: 10-

Primary Outcome(s)

Primary end point(s): Change in liver enzyme measurements from baseline to Week 12 (SD85)

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

Timepoint(s) of evaluation of this end point: Week 12 (SD85)

Secondary Outcome(s)

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 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

Secondary ID(s)

NI-0801-03

Source(s) of Monetary Support

NOVIMMUNE BV