E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Primary Biliary Cirrhosis (PBC) |
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E.1.1.1 | Medical condition in easily understood language |
Primary biliary cirrhosis is inflammation and destruction of the bile ducts of the liver, which blocks the flow of bile. This obstruction damages liver cells and leads to scarring called cirrhosis. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10036680 |
E.1.2 | Term | Primary biliary cirrhosis |
E.1.2 | System Organ Class | 100000004871 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the safety and tolerability of FFP104 in PBC subjects following repeat doses of FFP104. |
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E.2.2 | Secondary objectives of the trial |
- Proportion of subjects with a 10% decrease in ALP from baseline values at 12 weeks after Day 0 - Proportion of subjects with a 25% and 40% decrease in ALP at Week 4, 8, 12 after Day 0 - Proportion of subjects with ALP < 1.67 from upper level of normal, an ALP decrease >15% and bilirubin within normal levels at Week 4, 8, 12 and 24 after Day 0 - Proportion of subjects with a biochemical response: ALP ≤ 3x ULN and AST ≤2 x ULN and bilirubin ≤1mg/dL at Week 4, 8, 12 and 24 after Day 0 - To evaluate the individual and mean changes in serum ALP, ALT, AST, bilirubin, albumin, and GGT over time after Day 0 at Weeks 2, 4, 8, 12, 16 and 24 - To evaluate changes from baseline with Mayo Risk Score at 4, 8, 12, and 24 weeks - To evaluate changes from baseline in PBC-40 Quality of Life (QoL) at 12 and 24 weeks - To evaluate changes from baseline in pruritus using the Visual Analog Scale at 12 and 24 weeks - To evaluate changes in the Pharmacokinetics over time from baseline
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- 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 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 5 x ULN inclusive. - Be on a stable dose of 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) |
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E.4 | Principal exclusion criteria |
- Laboratory Screening results: a) ALT >5x ULN b) AST >5x ULN c) Total bilirubin >2x ULN. Isolated bilirubin >2x ULN is acceptable if bilirubin is fractionated and direct bilirubin <35% d) Total WBC <3000 cells/mm3 e) Absolute neutrophil count (ANC) <1500 cells/mm3 f) Platelet count <100,000/mm3 g) Prothrombin time (international normalized ratio (INR) >1.2 - 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 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 from Screening 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). - Prohibited medications 12 months prior to Screening: antibodies or immunotherapy directed against interleukins or other cytokines or chemokines. - Subjects with recurrent bacterial infections (as judged by the Investigator) within 6 months prior to Screening of FFP104), active bacterial, fungal or mycobacterial infections observed during - Screening, or any recent episode of infection requiring hospitalizations or treatment with antibiotics (within the 3 months prior to Screening). - History of malignancy, with the exception of resected basal cell carcinoma, squamous cell carcinoma of the skin, or resected cervical atypia or carcinoma in situ. - Immunization with a live vaccine within 4 weeks of Screening, with the exception of influenza vaccine and no planned immunizations within the period of the study - Known clinically significant cardiac disease (e.g., myocardial infarction or stroke, unstable angina, claudication, etc.), or evidence of a clinically significant electrocardiogram (ECG) abnormality within the previous 12 months prior to Screening. - Subjects with evidence of other serious, significant, acute or chronic medical or psychiatric illness that, in the judgment of the Investigator, could compromise subject safety, limit the subject's ability to complete the study, and/or compromise the objectives of the study. - History of recent (within 12 months of Screening) alcohol or drug abuse. - Use of other immunosuppressive medications 4 weeks prior to Screening. - Active tuberculosis (TB) in the past or currently, suspected TB which is presently receiving treatment or prophylactic therapy, has a positive TB test (as defined by local biological requirements), or any significant abnormality on chest X-ray within 3 months prior to Screening. - Subjects who have planned surgery during the study period or have undergone major surgery within the 3 months prior to Screening. - Known clinically significant allergy or known hypersensitivity to drugs that, in the opinion of the Investigator, may affect the patient's safety. - Known sensitivity to any component of the study drug or previous sensitivity reaction or other clinically significant reaction to intravenous medications or biologic therapy. - Participated in another clinical trial within the past 30 days prior to Screening, or is still within a washout period of a previous clinical trial, or has previously received FFP104 (PG102) or ch5D12 in this or any study.
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E.5 End points |
E.5.1 | Primary end point(s) |
This is an exploratory study to evaluate the safety and tolerability, pharmacokinetics and efficacy of FFP104. The general strategy of the analysis will be to examine the data summaries for any trends amongst the dose levels. No formal hypothesis testing will be conducted. Exploratory comparisons between dose cohorts can be performed, using non-parametrical statistical methods. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 19 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 21 |