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Safety, Tolerability, and Efficacy of a Combination Treatment of Tropifexor (LJN452) and Cenicriviroc (CVC) in Adult Patients With Nonalcoholic Steatohepatitis (NASH) and Liver Fibrosis. (TANDEM) (TANDEM)

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ClinicalTrials.gov Identifier: NCT03517540
Recruitment Status : Recruiting
First Posted : May 7, 2018
Last Update Posted : January 9, 2019
Sponsor:
Collaborator:
Allergan
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
The purpose of this study is to assess the safety, tolerability, and efficacy of a combination treatment of tropifexor (LJN452) and cenicriviroc (CVC) in adult patients with nonalcoholic steatohepatitis (NASH) and liver fibrosis.

Condition or disease Intervention/treatment Phase
Non-alcoholic Steatohepatitis Drug: Tropifexor (LJN452) Drug: Cenicriviroc (CVC) Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Multicenter Study to Assess the Safety, Tolerability, and Efficacy of a Combination Treatment of Tropifexor (LJN452) and Cenicriviroc (CVC) in Adult Patients With Nonalcoholic Steatohepatitis (NASH) and Liver Fibrosis
Actual Study Start Date : September 11, 2018
Estimated Primary Completion Date : July 27, 2020
Estimated Study Completion Date : July 27, 2020


Arm Intervention/treatment
Experimental: Arm A: Tropifexor (LJN452) - Dose 1 Drug: Tropifexor (LJN452)
Comparison with monotherapy and different combination doses

Experimental: Arm B: Cenicriviroc (CVC) Drug: Cenicriviroc (CVC)
Comparison with monotherapy and different combination doses

Experimental: Arm C: Tropifexor (LJN452) Dose 1 + CVC Drug: Tropifexor (LJN452)
Comparison with monotherapy and different combination doses

Drug: Cenicriviroc (CVC)
Comparison with monotherapy and different combination doses

Experimental: Arm D: Tropifexor Dose 2 + CVC Drug: Tropifexor (LJN452)
Comparison with monotherapy and different combination doses

Drug: Cenicriviroc (CVC)
Comparison with monotherapy and different combination doses




Primary Outcome Measures :
  1. Number of participants with Adverse Events [ Time Frame: 48 Weeks ]
    Occurrence of adverse events and serious adverse events


Secondary Outcome Measures :
  1. Proportion of participants who have at least a one point improvement in fibrosis [ Time Frame: baseline to 48 Weeks ]
    Efficacy of tropifexor + CVC in patients with Nonalcoholic steatohepatitis (NASH) with fibrosis stage F2/F3 as assessed by histological improvement after 48 weeks of treatment compared to monotherapies (tropifexor and CVC) compared to baseline biopsy

  2. Proportion of participants with resolution of steatohepatitis [ Time Frame: baseline to 48 weeks ]
    Efficacy of tropifexor + CVC in patients with Nonalcoholic steatohepatitis (NASH) with fibrosis stage F2/F3 as assessed by histological improvement after 48 weeks of treatment compared to monotherapies (tropifexor and CVC) compared to baseline biopsy



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Written informed consent Male and female patients 18 years or older (at the time of the screening visit). Patients must weigh at least 50 kg (110 lb) and no more than 200 kg (440 lb) to participate in the study.

Able to communicate well with the investigator, to understand and comply with the requirements of the study.

Adequate liver biopsy sample for evaluation by Central Reader. Presence of NASH as demonstrated by histologic evidence based on liver biopsy - NASH with fibrosis stage F2/F3, demonstrated on liver biopsy during the screening period. Alternatively, a historical biopsy can be used if performed within 6 months prior to screening.

Exclusion Criteria:

Use of other investigational drugs within 5 half-lives of enrollment or within 30 days whichever is longer.

History of hypersensitivity to any of the study drugs or its excipients or to drugs of similar chemical classes.

Previous exposure to elafibranor, CVC, tropifexor, obeticholic acid (OCA), LMB763 or other FXR agonist.

Participated in a clinical trial and treated with any investigational product being evaluated for the treatment of liver fibrosis or NASH in the 6 months before screening.

Patients taking medications prohibited by the protocol. History of treated or untreated malignancy of any organ system, other than localized basal cell carcinoma of the skin or treated cervical intraepithelial neoplasia, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases .

Pregnant or nursing (lactating) women. Women of child-bearing potential. Current or history of significant alcohol consumption for a period of more than 3 consecutive months within 1 year prior to screening (significant alcohol consumption is defined as more than 20 g/day in females and more than 30 g/day in males, on average) and/or a score on the modified AUDIT questionnaire ≥ 8.

Inability to reliably quantify alcohol consumption. History or evidence of ongoing drug abuse, within the last 6 months prior to randomization.

Prior or planned (during the study) bariatric surgery. Uncontrolled diabetes defined as HbA1c ≥ 9% at screening Clinical evidence of hepatic decompensation or severe liver impairment. Previous diagnosis of other forms of chronic liver disease. Calculated eGFR less than 60 mL/min (using the MDRD formula). History of biliary diversion History of liver transplantation or planned liver transplant. Known positivity for HIV. History or current diagnosis of ECG abnormalities indicating significant risk of safety for the patient to participate.

History of inflammatory bowel disease. Patients who are not candidates for liver biopsy. Presence of cirrhosis on liver biopsy (F4 by NASH CRN System) or medical history Patients with an abnormal platelet count (referring to reference ranges from the central lab).


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03517540


Contacts
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Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111

  Show 29 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Allergan

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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03517540     History of Changes
Other Study ID Numbers: CLJC242A2201J
2017-004208-24 ( EudraCT Number )
LJC242A2201J ( Other Identifier: Novartis )
First Posted: May 7, 2018    Key Record Dates
Last Update Posted: January 9, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com


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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Steatohepatitis
NASH
NAFLD
Fatty Liver Disease
Liver

Additional relevant MeSH terms:
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Fatty Liver
Liver Cirrhosis
Non-alcoholic Fatty Liver Disease
Liver Diseases
Digestive System Diseases
TAK-652
CCR5 Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents