Primary Biliary CirrhosisPhase 1/2NCT02193360
Pilot Study of FFP104 Dose Escalation in PBC Subjects
A Phase 1/2 study testing FFP104 in people with Primary Biliary Cirrhosis, run by Fast Forward Pharmaceuticals at 5 sites in 2 countries.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Primary Biliary Cirrhosis
- What is being tested?
- FFP104
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 5 sitesin 2 countries
- Study dates
- May 2015to Dec 2017
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 28Show fewer
- 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)
- 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 first dose 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 first dose)
- 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 immunisations 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 study) 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 to 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
Trial locations and contacts
5 sites in 2 countries.
5 sites in 2 countries
United Kingdom3 sites, 3 recruiting
- Recruiting
University Hospital Birmingham
Birmingham
G Hirschfield, MD, G.Hirschfield@bham.ac.uk
- Recruiting
Royal Free Hospital
London
D Thorburn, MD, douglas.thorburn@nhs.net
- Recruiting
Newcastle upon Tyne Hospitals
Newcastle upon Tyne
D Jones, MD, 0191 213 7210
Netherlands2 sites, 1 recruiting
- Active, not recruiting
Amsterdam Medical Center
Amsterdam, 1100 DD
- Recruiting
Erasmus University Medical Center
Rotterdam
H R van Buuren, MD, mdlpoli@erasmusmc.nl
H R van Buuren, MD
About this study
Official title: A Phase I/II, Open Label, Multicenter, Pilot Dose Escalation Study to Evaluate the Safety, Tolerability and Pharmacodynamics of FFP104 in Subjects Previously Diagnosed With Primary Biliary Cirrhosis (PBC)
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
- Being tested
- FFP104
- Keywords
- Inflammation, PBC
- Medical subject headings
- Liver Cirrhosis, Biliary, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FFP104Drug
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.
| Study group | Role | What they receive |
|---|---|---|
| Single arm Dose Escalation | Experimental | Not described Receives: Drug: FFP104 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Measured: Week 12
Proportion of subjects with a 25 and 40% decrease in ALP from baseline
Measured: 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
Measured: 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
Measured: Weeks 4, 8, 12 and 24
To evaluate the individual and mean changes in serum liver biochemistry from baseline
Evaluation of individual and mean changes in lab values (serum ALP, AST, bilirubin, albumin and gamma glutamyl transpeptidase (GGT)) over time from baseline values
Measured: Weeks 2, 4, 8, 12, 16 and 24
To evaluate changes from baseline with Mayo Risk Score
Measured: Weeks 4, 8, 12 and 24
To evaluate changes from baseline in the Patient Report Outcome PBC-40 Quality of Life
Measured: Weeks 12 and 24
To evaluate changes from baseline in pruritus using the Visual Analog Scale (VAS)
Measured: Weeks 12 and 24
To evaluate changes from baseline in fatigue using the VAS
Measured: Weeks 12 and 24
To evaluate changes in serum FFP104 levels from baseline
Measured: over time
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jul 2014 (estimated)
- Study startMay 2015
- Primary completionAug 2017 (estimated)
- Study completionDec 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Primary Biliary CirrhosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fast Forward Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02193360
- Sponsor's protocol ID
- FFP104-001
- Other IDs
- 2014-001638-27, 2014
- Status last verified
- Aug 2016
- First submitted
- 11 Jul 2014
- Last updated
- 24 Aug 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 24 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II, Open Label, Multicenter, Pilot Dose Escalation Study to Evaluate the Safety, Tolerability and Pharmacodynamics of FFP104 in Subjects Previously Diagnosed With Primary Biliary Cirrhosis (PBC)
- ClinicalTrials.gov ID
- NCT02193360
- Acronym / sponsor ID
- FFP104-001
- Conditions
- Primary Biliary Cirrhosis
- Keywords
- Inflammation, PBC
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- Fast Forward PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- May 2015
- Primary completion
- Aug 2017 (estimated)
- Study completion
- Dec 2017 (estimated)
- First posted
- 17 Jul 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine the initial safety, tolerability and pharmacodynamics of the CD40-antagonist Mab, FFP104, in subjects with PBC
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single arm Dose Escalation | Experimental | Drug: FFP104 |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (28 listed)
- Laboratory screening results
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FFP104Cohorts 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. | Drug | Single arm Dose Escalation |
Primary outcome
Safety and tolerability of FFP104 in PBC subjects following repeat doses of FFP104
Time frame: Days 1, 3, 5 and weeks 2 - 12, 14, 16 and 24
Safety outcomes include abbreviated physical examination, treatment emergent adverse events (TEAE), clinically significant changes in clinical haematology, clinical chemistry, and urinalysis.
10 secondary outcomes
Proportion of subjects with a 10% decrease in Alkaline Phosphatase (ALP) from baseline values
Time frame: Week 12
Proportion of subjects with a 25 and 40% decrease in ALP from baseline
Time frame: 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
Time frame: 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
Time frame: Weeks 4, 8, 12 and 24
To evaluate the individual and mean changes in serum liver biochemistry from baseline
Time frame: Weeks 2, 4, 8, 12, 16 and 24
To evaluate changes from baseline with Mayo Risk Score
Time frame: Weeks 4, 8, 12 and 24
To evaluate changes from baseline in the Patient Report Outcome PBC-40 Quality of Life
Time frame: Weeks 12 and 24
To evaluate changes from baseline in pruritus using the Visual Analog Scale (VAS)
Time frame: Weeks 12 and 24
To evaluate changes from baseline in fatigue using the VAS
Time frame: Weeks 12 and 24
To evaluate changes in serum FFP104 levels from baseline
Time frame: over time
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Aug 2016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
5 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing FFP104 in people with Primary Biliary Cirrhosis, run by Fast Forward Pharmaceuticals at 5 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 24 Aug 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United Kingdom, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and tolerability of FFP104 in PBC subjects following repeat doses of FFP104 (time frame: Days 1, 3, 5 and weeks 2 - 12, 14, 16 and 24). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Aug 2016.