Pilot Study of FFP104 Dose Escalation in PBC Subjects

NCT02193360 | Unknown Phase 1 DMC

• 2 other identifiers: FFP104-0012014-001638-27
• Study Type: interventional
• Target: 24
• Locations: 2 countries
• Sites: 5

Brief Summary

The purpose of this study is to determine the initial safety, tolerability and pharmacodynamics of the CD40-antagonist Mab, FFP104, in subjects with PBC

Conditions

Primary Biliary Cirrhosis

Keywords

Inflammation; PBC

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability of FFP104 in PBC subjects following repeat doses of FFP104

  Safety outcomes include abbreviated physical examination, treatment emergent adverse events (TEAE), clinically significant changes in clinical haematology, clinical chemistry, and urinalysis.

  Days 1, 3, 5 and weeks 2 - 12, 14, 16 and 24

Secondary Outcomes (10)

• Proportion of subjects with a 10% decrease in Alkaline Phosphatase (ALP) from baseline values

  Week 12

• Proportion of subjects with a 25 and 40% decrease in ALP from baseline

  Weeks 4, 8 and 12

• Proportion of subjects with ALP<1.67 from upper limit of normal (ULN), an ALP decrease >15% and bilirubin within normal levels

  Weeks 4, 8, 12 and 24

• Proportion of subjects with a biochemical response according to 'Paris I' criteria: ALP≤ 3x ULN and Aspartate Transaminase (AST) ≤2x ULN and bilirubin ≤1mg/dL

  Weeks 4, 8, 12 and 24

• To evaluate the individual and mean changes in serum liver biochemistry from baseline

  Weeks 2, 4, 8, 12, 16 and 24

Study Arms (1)

Single arm Dose Escalation

EXPERIMENTAL

Drug: FFP104

Interventions

FFP104 DRUG

Cohorts receiving multiple weekly or biweekly i.v. doses of FFP104. FFP104 dose levels: 1.0, 2.5 and 5.0 mg/kg. Subjects will be treated for 12 weeks and then followed for safety and efficacy assessments for an additional 12 weeks.

Single arm Dose Escalation

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female Age between 18 and 75 years of age inclusive at the time of signing the informed consent
• Established diagnosis of PBC according to the EASL criteria (European Association for the Study of the Liver 2009): A diagnosis of PBC can be made with confidence in adult patients with otherwise unexplained elevation of ALP and presence of anti-mitochondrial antibody (AMA≥1:40), and/or AMA type M2. A liver biopsy is not essential for the diagnosis of PBC in these patients, but allows activity and stage of the disease to be assessed.
• Having a screening ALP serum level between 1.67 and 5x ULN inclusive.
• Be on a stable dose of ursodeoxycholic acid (UDCA) 12-20 mg/kg/day for at least 3 months prior to Screening or intolerant of UDCA in the opinion of the investigator (no UDCA for at least 8 weeks prior to Screening).
• Are not pregnant or breast feeding and do not plan to become pregnant or father a child during the study. Female subjects (of childbearing potential) must be willing to use two medically accepted forms of contraception throughout the study and must be willing to submit to pregnancy test(s). Male subjects must agree to use medically accepted contraception methods with their partners throughout the study as described above, unless they have had a prior vasectomy.
• Has the ability to communicate adequately with the study staff and to comply with the requirements of the entire study, with the help of a caregiver, if applicable.

You may not qualify if:

• Laboratory screening results
• alanine transaminase (ALT) \>5x ULN
• aspartate transaminase (AST) \>5x ULN
• Total bilirubin \>2x ULN. Isolated bilirubin \>2x ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%
• Total white blood cells (WBC) \<3000 cells/mm3
• Absolute neutrophil count (ANC) \<1500 cells/mm3
• Platelet count \<100,000/mm3
• Prothrombin time (international normalized ratio (INR)\> 1.2
• Body mass index (BMI) ≥35 or suspected to have relevant nonalcoholic fatty liver disease (NAFLD) as based on the judgment of the Investigator at screening
• Subject has a history of, or current viral hepatitis B or C (including hepatitis B surface antigen \[HBsAg\], hepatitis B core antibody and hepatitis C virus (HCV) antibody \[anti-HCV\] positivity), or a positive HIV antibody screen at time of screening
• Recipients of liver or other organ transplantation or anticipated need for orthotropic organ transplantation in one year as determined by the Mayo Risk Score
• Co-existing liver or biliary diseases, such as primary sclerosing cholangitis, choledocholithiasis, acute or chronic hepatitis, autoimmune hepatitis, alcoholic liver disease, nonalcoholic steatohepatitis (NASH), acute infection of bile duct system or gall bladder, history of gastrointestinal bleeding (secondary to portal hypertension), cholangiocarcinoma diagnosed or suspected liver cancers
• Recurrent variceal hemorrhage, uncontrolled encephalopathy, Child-Pugh Class B/C, Esophageal Varices, or refractory ascites within the previous 6 months of Screening (defined as date informed consent signed)
• Have a family history (more than one first degree relative) of multiple thrombotic events or a personal history of any venous or arterial thrombotic event including deep vein thrombosis, stroke, myocardial infarction, pulmonary embolus, or peripheral arterial thromboembolic events
• Prohibited medications 6 months prior to Screening: azathioprine, colchicine, cyclosporine, methotrexate, mycophenolate mofetil, pentoxifylline; fenofibrate or other fibrates; budesonide and other systemic corticosteroids; potentially hepatotoxic drugs (including α-methyl-dopa, sodium valproic acid, isoniazid, or nitrofurantoin)

Sponsors & Collaborators

• Fast Forward Pharmaceuticals: lead

Study Sites (5)

Amsterdam Medical Center

Amsterdam, 1100 DD, Netherlands

ACTIVE NOT RECRUITING

Erasmus University Medical Center

Rotterdam, Netherlands

RECRUITING

University Hospital Birmingham

Birmingham, United Kingdom

RECRUITING

Royal Free Hospital

London, United Kingdom

RECRUITING

Newcastle upon Tyne Hospitals

Newcastle upon Tyne, United Kingdom

RECRUITING

MeSH Terms

Conditions

Liver Cirrhosis, Biliary; Inflammation

Condition Hierarchy (Ancestors)

Cholestasis, Intrahepatic; Cholestasis; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Liver Diseases; Liver Cirrhosis; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 11, 2014
• First Posted: July 17, 2014
• Study Start: May 1, 2015
• Primary Completion: August 1, 2017
• Study Completion: December 1, 2017
• Last Updated: August 24, 2016

Record last verified: 2016-08

Locations

GB (3); NL (2)