Non-alcoholic Steatohepatitis (NASH)Phase 2TANDEMNCT03517540
Study of Safety, Tolerability, and Efficacy of a Combination Treatment of LJN452 and CVC in Adult Patients With NASH and Liver Fibrosis
A Phase 2 study testing Tropifexor (LJN452) and Cenicriviroc (CVC) in people with Non-alcoholic Steatohepatitis (NASH), run by Novartis Pharmaceuticals at 65 sites in 17 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-alcoholic Steatohepatitis (NASH)
- What is being tested?
- Tropifexor (LJN452) and Cenicriviroc (CVC)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 193 participants
- Where
- 65 sitesin 17 countries
- Study dates
- 11 Sep 2018to 15 Oct 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 9Show fewer
- 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).
Trial locations and contacts
65 sites in 17 countries.
65 sites in 17 countries
United States27 sites
Novartis Investigative Site
Atlanta, Georgia, 30309
Novartis Investigative Site
Atlanta, Georgia, 30312
Novartis Investigative Site
Chandler, Arizona, 85224
Novartis Investigative Site
Chattanooga, Tennessee, 37404
Novartis Investigative Site
Chicago, Illinois, 60637-1470
Novartis Investigative Site
Concord, North Carolina, 28027
Novartis Investigative Site
Coronado, California, 92118
Novartis Investigative Site
Dallas, Texas, 75208-2312
Novartis Investigative Site
Durham, North Carolina, 27710
Novartis Investigative Site
Germantown, Tennessee, 38138
Novartis Investigative Site
Hermitage, Tennessee, 37076
Novartis Investigative Site
Indianapolis, Indiana, 46237
Novartis Investigative Site
Los Angeles, California, 90048
Novartis Investigative Site
Los Angeles, California, 90057
Novartis Investigative Site
Marietta, Georgia, 30060
Novartis Investigative Site
Metairie, Louisiana, 70006
Novartis Investigative Site
Morehead City, North Carolina, 28557
Novartis Investigative Site
Murray, Utah, 84107
Novartis Investigative Site
North Little Rock, Arkansas, 72117
Novartis Investigative Site
Pasadena, California, 91105
Novartis Investigative Site
Providence, Rhode Island, 02905
Novartis Investigative Site
Rialto, California, 92377
Novartis Investigative Site
Richmond, Virginia, 23249
Novartis Investigative Site
Richmond, Virginia, 23298
Novartis Investigative Site
San Antonio, Texas, 78215
Novartis Investigative Site
Seattle, Washington, 98104
Novartis Investigative Site
Shreveport, Louisiana, 71103
Canada5 sites
Novartis Investigative Site
Chicoutimi, Quebec, G7H 7K9
Novartis Investigative Site
Montreal, Quebec, H4A 3J1
Novartis Investigative Site
Toronto, Ontario, M5G 2C4
Novartis Investigative Site
Toronto, Ontario, M6H 3MI
Novartis Investigative Site
Vancouver, British Columbia, V6Z 2K5
Italy5 sites
Novartis Investigative Site
Milan, 20112
Novartis Investigative Site
Modena, Itlay, 41126
Novartis Investigative Site
Palermo, PA, 90127
Novartis Investigative Site
Roma, RM, 00168
Novartis Investigative Site
Verona, VR, 37126
Spain4 sites
Novartis Investigative Site
Barcelona, Catalonia, 08035
Novartis Investigative Site
Barcelona, Catalonia, 08036
Novartis Investigative Site
Santander, Cantabria, 39008
Novartis Investigative Site
Valencia, Valencia, 46026
Argentina3 sites
Novartis Investigative Site
Caba, Buenos Aires, C1280AEB
Novartis Investigative Site
CABA, Buenos Aires, C1181ACH
Novartis Investigative Site
San Juan Bautista, Buenos Aires, C1073ABA
France3 sites
Novartis Investigative Site
Paris, 75651
Novartis Investigative Site
Pessac, 33604
Novartis Investigative Site
Strasbourg, 67098
United Kingdom3 sites
Novartis Investigative Site
Aberdeen, AB25 2ZN
Novartis Investigative Site
High Heaton, Newcastle Upon Tyne, NE7 7DN
Novartis Investigative Site
Torquay, TQ2 7AA
Belgium2 sites
Novartis Investigative Site
Edegem, Antwerpen, 2650
Novartis Investigative Site
Leuven, 3000
Germany2 sites
Novartis Investigative Site
Mainz, 55131
Novartis Investigative Site
Würzburg, 97080
Russia2 sites
Novartis Investigative Site
Moscow, 101990
Novartis Investigative Site
Moscow, 109544
Singapore2 sites
Novartis Investigative Site
Singapore, 117549
Novartis Investigative Site
Singapore, 169608
Turkey (Türkiye)2 sites
Novartis Investigative Site
Izmir, 35100
Novartis Investigative Site
Pendik / Istanbul, Turkey, 34899
India1 site
Novartis Investigative Site
New Delhi, National Capital Territory of Delhi, 110070
About this study
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
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.
- Conditions
- Non-alcoholic Steatohepatitis (NASH)
- Being tested
- Tropifexor (LJN452), Cenicriviroc (CVC)
- Keywords
- Steatohepatitis, NASH, NAFLD, Fatty Liver Disease, Liver, Liver fibrosis
- Medical subject headings
- Non-alcoholic Fatty Liver Disease, Fatty Liver, Liver Cirrhosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tropifexor (LJN452)Drug
Also called LJN452
Comparison with monotherapy and different combination doses
Cenicriviroc (CVC)Drug
Also called CVC
Comparison with monotherapy and different combination doses
| Study group | Role | What they receive |
|---|---|---|
| Arm A: Tropifexor (LJN452) - Dose 1 | Experimental | tropifexor 140 mcg, once daily; given orally Receives: Drug: Tropifexor (LJN452) |
| Arm B: Cenicriviroc (CVC) | Experimental | CVC 150 mg, once daily; given orally Receives: Drug: Cenicriviroc (CVC) |
| Arm C: Tropifexor (LJN452) Dose 1 + CVC | Experimental | tropifexor 140 mcg + CVC 150 mg, once daily; given orally Receives: Drug: Tropifexor (LJN452); Drug: Cenicriviroc (CVC) |
| Arm D: Tropifexor Dose 2 + CVC | Experimental | tropifexor 90 mcg + CVC 150 mg, once daily; given orally Receives: Drug: Tropifexor (LJN452); Drug: Cenicriviroc (CVC) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Adverse Events
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
Measured: 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
Secondary outcomes (2)
Proportion of Participants Who Have at Least a One Point Improvement in Fibrosis
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
Measured: baseline to 48 Weeks
Proportion of Participants With Resolution of Steatohepatitis
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
Measured: baseline to 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 May 2018
- Study start11 Sep 2018
- Primary completion15 Sep 2020
- Study completion15 Oct 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Non-alcoholic Steatohepatitis (NASH)Studies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 193 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Allergan
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03517540
- Sponsor's protocol ID
- CLJC242A2201J
- Other IDs
- 2017-004208-24, LJC242A2201J, 2017
- Acronym
- TANDEM
- Status last verified
- Apr 2022
- First submitted
- 9 Apr 2018
- Last updated
- 29 Apr 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: 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
Publications
Pedrosa M, Seyedkazemi S, Francque S, Sanyal A, Rinella M, Charlton M, Loomba R, Ratziu V, Kochuparampil J, Fischer L, Vaidyanathan S, Anstee QM. A randomized, double-blind, multicenter, phase 2b study to evaluate the safety and efficacy of a combination of tropifexor and cenicriviroc in patients with nonalcoholic steatohepatitis and liver fibrosis: Study design of the TANDEM trial. Contemp Clin Trials. 2020 Jan;88:105889. doi: 10.1016/j.cct.2019.105889. Epub 2019 Nov 13.
PubMed 31731005Parthasarathy G, Malhi H. Macrophage Heterogeneity in NASH: More Than Just Nomenclature. Hepatology. 2021 Jul;74(1):515-518. doi: 10.1002/hep.31790. Epub 2021 May 22. No abstract available.
PubMed 33666272
Study at a glance
From the registry record, last updated by the sponsor on 29 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03517540
- Acronym / sponsor ID
- TANDEM / CLJC242A2201J
- Conditions
- Non-alcoholic Steatohepatitis (NASH)
- Keywords
- Steatohepatitis, NASH, NAFLD, Fatty Liver Disease, Liver, Liver fibrosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 193 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Collaborators
- Allergan
- Study start
- 11 Sep 2018 (actual)
- Primary completion
- 15 Sep 2020 (actual)
- Study completion
- 15 Oct 2020 (actual)
- First posted
- 7 May 2018 (actual)
- Results
- Posted 12 Nov 2021
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 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Arm A: Tropifexor (LJN452) - Dose 1 | Experimental | Drug: Tropifexor (LJN452)tropifexor 140 mcg, once daily; given orally |
| Arm B: Cenicriviroc (CVC) | Experimental | Drug: Cenicriviroc (CVC)CVC 150 mg, once daily; given orally |
| Arm C: Tropifexor (LJN452) Dose 1 + CVC | Experimental | Drug: Tropifexor (LJN452), Drug: Cenicriviroc (CVC)tropifexor 140 mcg + CVC 150 mg, once daily; given orally |
| Arm D: Tropifexor Dose 2 + CVC | Experimental | Drug: Tropifexor (LJN452), Drug: Cenicriviroc (CVC)tropifexor 90 mcg + CVC 150 mg, once daily; given orally |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (9 listed)
- 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 .
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 |
|---|---|---|
| Tropifexor (LJN452)Also: LJN452Comparison with monotherapy and different combination doses | Drug | Arm A: Tropifexor (LJN452) - Dose 1, Arm C: Tropifexor (LJN452) Dose 1 + CVC, Arm D: Tropifexor Dose 2 + CVC |
| Cenicriviroc (CVC)Also: CVCComparison with monotherapy and different combination doses | Drug | Arm B: Cenicriviroc (CVC), Arm C: Tropifexor (LJN452) Dose 1 + CVC, Arm D: Tropifexor Dose 2 + CVC |
Primary outcome
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
2 secondary outcomes
Proportion of Participants Who Have at Least a One Point Improvement in Fibrosis
Time frame: baseline to 48 Weeks
Proportion of Participants With Resolution of Steatohepatitis
Time frame: baseline to 48 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Apr 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 31731005Pedrosa M, Seyedkazemi S, Francque S, Sanyal A, Rinella M, Charlton M, Loomba R, Ratziu V, Kochuparampil J, Fischer L, Vaidyanathan S, Anstee QM. A randomized, double-blind, multicenter, phase 2b study to evaluate the safety and efficacy of a combination of tropifexor and cenicriviroc in patients with nonalcoholic steatohepatitis and liver fibrosis: Study design of the TANDEM trial. Contemp Clin Trials. 2020 Jan;88:105889. doi: 10.1016/j.cct.2019.105889. Epub 2019 Nov 13.
- Derived from this study: PubMed 33666272Parthasarathy G, Malhi H. Macrophage Heterogeneity in NASH: More Than Just Nomenclature. Hepatology. 2021 Jul;74(1):515-518. doi: 10.1002/hep.31790. Epub 2021 May 22. No abstract available.
- A Plain Language Trial Summary is available on novctrd.comLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided. 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
Related trials for Non-alcoholic Steatohepatitis (NASH)
Not yet recruiting
Efficacy of Carnitine Complex in Improving Hepatic Steatosis in Potential Liver Donors
Hepatic Steatosis, Fatty Liver
RecruitingPhase 3
A Study Evaluating Efruxifermin in Subjects With Non-Cirrhotic Nonalcoholic Steatohepatitis (NASH)/Metabolic Dysfunction-Associated Steatohepatitis (MASH) and Fibrosis
NASH With Fibrosis, MASH With Fibrosis
Recruiting
NAFLD Clinical Care Pathway
NAFLD, MASLD
RecruitingPhase 3
Trial to Evaluate ALN-CIDEB in Adults With Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
Metabolic Dysfunction-Associated Steatotic Liver Disease, MASLD
RecruitingPhase 1
A Study of Efimosfermin Alfa in Adults With Hepatic Impairment
Non-alcoholic Fatty Liver Disease
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.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
65 sites in 17 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tropifexor (LJN452) and Cenicriviroc (CVC) in people with Non-alcoholic Steatohepatitis (NASH), run by Novartis Pharmaceuticals at 65 sites in 17 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 3 inclusion and 9 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: finished, as of the sponsor's last update on 29 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 65 sites in United States, Canada, Italy, Spain, Argentina and 12 more countries. 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 phase mean?
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?
Yes. Results are posted in the registry (first posted 12 Nov 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03517540, which also lists 2 linked publications.
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 29 Apr 2022.