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Study of Safety, Tolerability, and Efficacy of a Combination Treatment of LJN452 and CVC in Adult Patients With NASH and Liver Fibrosis (TANDEM)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03517540
Recruitment Status : Completed
First Posted : May 7, 2018
Results First Posted : November 12, 2021
Last Update Posted : April 29, 2022
Sponsor:
Collaborator:
Allergan
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE April 9, 2018
First Posted Date  ICMJE May 7, 2018
Results First Submitted Date  ICMJE October 14, 2021
Results First Posted Date  ICMJE November 12, 2021
Last Update Posted Date April 29, 2022
Actual Study Start Date  ICMJE September 11, 2018
Actual Primary Completion Date September 15, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 14, 2021)
Number of Participants With Adverse Events [ Time Frame: AEs were collected from first dose of study treatment until end of study treatment at week 48 and then up to maximum duration of 66 weeks ]
Occurrence of adverse events and serious adverse events Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment and then up to 66 weeks
Original Primary Outcome Measures  ICMJE
 (submitted: April 24, 2018)
Number of participants with Adverse Events [ Time Frame: 48 Weeks ]
Occurrence of adverse events and serious adverse events
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 14, 2021)
  • 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
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: April 24, 2018)
  • 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
  • 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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Safety, Tolerability, and Efficacy of a Combination Treatment of LJN452 and CVC in Adult Patients With NASH and Liver Fibrosis
Official Title  ICMJE 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
Brief Summary The purpose of this study was 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Non-alcoholic Steatohepatitis (NASH)
Intervention  ICMJE
  • Drug: Tropifexor (LJN452)
    Comparison with monotherapy and different combination doses
    Other Name: LJN452
  • Drug: Cenicriviroc (CVC)
    Comparison with monotherapy and different combination doses
    Other Name: CVC
Study Arms  ICMJE
  • Experimental: Arm A: Tropifexor (LJN452) - Dose 1
    tropifexor 140 mcg, once daily; given orally
    Intervention: Drug: Tropifexor (LJN452)
  • Experimental: Arm B: Cenicriviroc (CVC)
    CVC 150 mg, once daily; given orally
    Intervention: Drug: Cenicriviroc (CVC)
  • Experimental: Arm C: Tropifexor (LJN452) Dose 1 + CVC
    tropifexor 140 mcg + CVC 150 mg, once daily; given orally
    Interventions:
    • Drug: Tropifexor (LJN452)
    • Drug: Cenicriviroc (CVC)
  • Experimental: Arm D: Tropifexor Dose 2 + CVC
    tropifexor 90 mcg + CVC 150 mg, once daily; given orally
    Interventions:
    • Drug: Tropifexor (LJN452)
    • Drug: Cenicriviroc (CVC)
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 31, 2020)
193
Original Estimated Enrollment  ICMJE
 (submitted: April 24, 2018)
200
Actual Study Completion Date  ICMJE October 15, 2020
Actual Primary Completion Date September 15, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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).

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Belgium,   Canada,   Czechia,   Egypt,   France,   Germany,   India,   Israel,   Italy,   Latvia,   Russian Federation,   Singapore,   Spain,   Turkey,   United Kingdom,   United States
Removed Location Countries Estonia,   Hong Kong,   Portugal,   Switzerland
 
Administrative Information
NCT Number  ICMJE NCT03517540
Other Study ID Numbers  ICMJE CLJC242A2201J
2017-004208-24 ( EudraCT Number )
LJC242A2201J ( Other Identifier: Novartis )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
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

Current Responsible Party Novartis ( Novartis Pharmaceuticals )
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Novartis Pharmaceuticals
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Allergan
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date April 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP