E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Liver fibrosis in Subjects with Nonalcoholic Steatohepatitis |
|
E.1.1.1 | Medical condition in easily understood language |
Fatty Liver where the cells in the liver have abnormal fat built-up and
built-up of scar tissue in the liver. |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10053219 |
E.1.2 | Term | Non-alcoholic steatohepatitis |
E.1.2 | System Organ Class | 10019805 - Hepatobiliary disorders |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is to provide open-label treatment with CVC to subjects who have previously participated in CVC studies. |
|
E.2.2 | Secondary objectives of the trial |
The secondary objective of this study is to assess the long-term safety of continued treatment with CVC for subjects who have previously participated in CVC studies. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
For a subject to be eligible for participation in this study, all of the following criteria must apply.
1. Subjects who have either:
• Completed both Treatment Period 1 and Treatment Period 2, of the
CENTAUR study (652-2-203), including a Year 2 liver biopsy
• Completed the AURORA study (3152-301-002) as a result of reaching
an adjudicated liver-related clinical outcome in Part 1 or Part 2 of the
study of:
o Histopathologic progression to cirrhosis
o Model for end-stage liver disease (MELD) score ≥ 15
o Ascites (requiring intervention, ie, large volume paracentesis ≥ 1L
or initiation of a diuretic)
o Hospitalization (as defined by a stay of ≥ 24 hours) for onset of:
variceal bleed, hepatic encephalopathy (defined by a West Haven Stage
of ≥ 2), spontaneous bacterial peritonitis (confirmed by diagnostic paracentesis with positive ascitic fluid bacterial culture)
2. Has been determined to be in a stable medical condition (minimum of 3 months from the date of the clinical event in AURORA to the Baseline Visit of this study) based on medical history or physical examination, in the opinion of investigator. Inclusion criterion applies only to subjects coming from the AURORA study (3152-301-002).
3. Must provide a signed written informed consent form
4. Females of child-bearing potential and males participating in the study must agree to use at least 2 approved barrier methods of contraception throughout the duration of the study and for 30 days after stopping study drug. Females who are postmenopausal must have documentation of cessation of menses for ≥ 12 months without an alternative medical cause. Follicle stimulating hormone (FSH) level in the postmenopausal range (≥ 30 mU/mL) may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy (HRT). However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.
a) Females on HRT and whose menopausal status is in doubt will be
required to use the contraception methods in Section 20.3 if they wish to continue their HRT during the
study. Otherwise, they must temporarily discontinue HRT to enable
confirmation of postmenopausal status before study enrollment. |
|
E.4 | Principal exclusion criteria |
A subject will not be eligible for participation in this study if any of the following criteria apply.
1. Any clinically significant change in the subject’s medical history or condition which, in the opinion of the investigator, would preclude administration of open-label CVC, including laboratory tests
2. Prior or planned liver transplantation
3. Other known causes of chronic liver disease, such as the following:
• Alcoholic liver disease
• Primary biliary cirrhosis
• Primary sclerosing cholangitis
• Autoimmune hepatitis
• Wilson’s disease, hemochromatosis, or iron overload
• Alpha-1-antitrypsis (A1AT) deficiency
4. Females who are pregnant or breastfeeding
5. Any other clinically significant disorders or prior therapy that, in the opinion of the investigator, would make the subject unsuitable for the
study or unable to comply with the dosing and protocol requirements.
6. Currently receiving or planning to use any other investigational NASH
treatment during the study
7. Known history of hepatocellular carcinoma (HCC) at any time, history
of malignancy within the past 5 years or ongoing malignancy other than:
basal cell carcinoma, resected noninvasive cutaneous squamous cell
carcinoma, or treated stage II or lower colorectal or breast cancer in
remission for ≥ 2 years and with low risk of recurrence (ie, Oncotype DX
12 gene recurrence score < 30 for stage II or lower colon cancer; earlystage, estrogen-receptor positive, HER2-negative breast cancers that haven't spread to the lymph nodes; Oncotype DX 21 gene recurrence score < 18 for early-stage invasive breast cancer; or Oncotype DX ductal carcinoma in situ [DCIS] 12 gene recurrence score < 39 for noninvasive breast cancer) |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Long-term safety assessment of CVC administration |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Once Cenicriviroc is commercially available or if development is discontinued |
|
E.5.2 | Secondary end point(s) |
Safety assessments including adverse events, hematology profile, chemistry profile, coagulation profile and serum chemistry |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
At baseline, and every 3 months thereafter until study discontinued |
|
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 | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
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 | 1 |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 150 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Australia |
Austria |
Belgium |
Brazil |
Canada |
Chile |
France |
Germany |
Greece |
Hong Kong |
Hungary |
Israel |
Italy |
Mexico |
New Zealand |
Peru |
Poland |
Portugal |
Singapore |
Spain |
Switzerland |
Taiwan |
United Kingdom |
United States |
|
E.8.7 | Trial has a data monitoring committee | No |
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
|
When the drug product becomes commercially available or if the study is discontinued by the Sponsor |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 6 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |