Nonalcoholic SteatohepatitisPhase 2NASHNCT02769091
A Study in Adult Patients With Nonalcoholic Steatohepatitis Who Also Have Type 2 Diabetes
A Phase 2 study testing TEV-45478 in people with Nonalcoholic Steatohepatitis and Type 2 Diabetes Mellitus, run by Teva Branded Pharmaceutical Products R&D, Inc..
Trial summary
The purpose of this study is to assess the effect of TEV-45478, as compared with placebo, on liver health and liver fat content in patients with T2DM who also have Nonalcoholic Steatohepatitis (NASH). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Nonalcoholic Steatohepatitis, Type 2 Diabetes Mellitus
- What is being tested?
- TEV-45478
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 30 Sep 2016to 28 Feb 2018
- Phase
- Phase 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- The patient is female or male and aged 18 to 65 years, inclusive with a history of Type 2 Diabetes Mellitus (T2DM) and on stable medication for diabetes or insulin or a combination thereof for at least 3 months prior to screening.
- The patient has a NASH Activity Score (NAS) of ≥4, with or without evidence of fibrosis, with a score of at least 1 in steatosis and lobular inflammation the subcomponents of NAS and a hepatocyte ballooning score of at least 1 score based on historical histological evaluation of liver biopsy within 12 months prior to randomization.
- The patient has a historical diagnosis of NASH, established no more than 12 months prior to randomization based on histology (liver biopsy).
- The patient has an ALT level at screening between 45 and 105 IU/L, inclusive, for women and between 55 and 120 IU/L, inclusive for men, at one other occasion during the 24-weeks prior to screening.
- The patient has an MRI determined liver fat fraction of equal to or higher than 6% at Screening
- Additional criteria apply, please contact the investigator for more information
Who cannot join
- The patient has a history of chronic liver disease other than NASH eg, chronic or acute hepatitis, autoimmune, viral (A, B, C), genetic hepatitis, drug induced hepatotoxicity, Wilson's disease, alcoholic liver diseases, or any other non-NASH active liver disease.
- The patient has active cancer or a history of a malignant disease (except basal cell carcinoma of the skin) within 5 years prior to screening or any history of bladder cancer.
- The patient had an unstable metabolic condition (ie, with a history of weight loss or weight gain of >5 kg within 24 weeks prior to screening)
- The patient has a history of bariatric surgery within 5 years prior to screening.
- The patient has received mercaptopurine or azathioprine previously within 1 year prior to screening
- The patient has taken within 7 days prior to the first dose of study drug (or is anticipated to take during the study) anticholinergic or other drugs known to affect gastrointestinal (GI) motility, proton-pump inhibitors, or other drugs known to affect gastric acidity or use of allopurinol.
Show all 17Show fewer
- The patient has received oral antibiotics within the last 4 weeks prior to randomization (day 1).
- The patient has received treatment within the last 30 days with any drugs known to induce or inhibit endogenous hepatic drug metabolism (eg, barbiturates, phenothiazines, cimetidine, carbamazepine) or anti-coagulant therapy (eg, heparin, warfarin, acenocoumarol).
- The patient has Type 1 Diabetes Mellitus (T1DM) or poorly controlled T2DM
- The patient has a body mass index (BMI) <25 kg/m2.
- The patient has a history of diabetic gastroparesis or has had gastric bypass surgery within the last 5 years.
- The patient has a history of pancreatitis.
- The patient has a history of persistent intestinal obstruction, bowel perforation, uncontrolled GI bleed or abdominal abscess or infection or toxic megacolon or inflammatory bowel disease (IBD)
- The patient has a history of coronary angioplasty, coronary stent placement, coronary bypass surgery, unstable angina, myocardial infarction, transient ischemic events, or stroke within 24-weeks prior to screening.
- The patient is classified as Class II-IV via New York Heart Association
- The patient has a history of drug abuse (defined as illicit drug use) or a history of excessive alcohol abuse (defined as regular or daily consumption of more than 2 alcoholic drinks per day for women or 3 alcoholic drinks per day for men) within 1 year prior to the screening visit.
- Additional criteria apply, please contact the investigator for more information
About this study
Official title: A 24-Week, Randomized, Double-blind, Placebo-controlled, Efficacy and Safety Study of 80 mg TEV-45478 Once Daily as Treatment in Adult Patients With Nonalcoholic Steatohepatitis (NASH) Who Also Have Type 2 Diabetes Mellitus - GN
The purpose of this study is to assess the effect of TEV-45478, as compared with placebo, on liver health and liver fat content in patients with T2DM who also have Nonalcoholic Steatohepatitis (NASH).
- Being tested
- TEV-45478, Placebo
- Medical subject headings
- Non-alcoholic Fatty Liver Disease, Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TEV-45478Drug
80 mg (2x40mg) tablets once daily for up to 24 weeks
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| TEV-45478 | Experimental | 80 mg (2x40mg) tablets once daily for up to 24 weeks Receives: Drug: TEV-45478 |
| Placebo | Placebo comparator | Matching placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
serum Alanine Transaminase (ALT) levels response, defined as ALT value within reference range of <35 IU/L for women and <40 IU/L for men
Measured: Week 24
liver fat response, defined as a reduction of ≥6% at week 24 compared to screening by the MRI-Proton Density Fat Fraction (PDFF)
Measured: Week 24
Percentage of Participants with Adverse Events
Measured: 24 weeks
Secondary outcomes (7)
percent change from baseline in ALT
Measured: Baseline, Week 24
percent change from baseline in ALT
Measured: Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24 (or early withdrawal)
percent change from baseline in Aspartate Aminotransferase (AST)
Measured: Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24 (or early withdrawal)
change from baseline in AST
Measured: Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24 (or early withdrawal)
change from baseline in ALT
Measured: Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24 (or early withdrawal)
Change from baseline in glycosylated hemoglobin ((HbA1c)
Measured: Baseline, Weeks 4, 12, and 24 (or early withdrawal)
Change from baseline in liver fibrosis measured using transient elastography (with Fibroscan)
Measured: Baseline, Week 24 (or early withdrawal)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 May 2016 (estimated)
- Study start30 Sep 2016
- Primary completion31 Jan 2018 (estimated)
- Study completion28 Feb 2018 (estimated)
Why it stopped: Business decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Nonalcoholic SteatohepatitisStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Teva Branded Pharmaceutical Products R&D, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Teva Medical Expert, MD, Study director, Teva Branded Pharmaceutical Products R&D, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02769091
- Sponsor's protocol ID
- TV45478-IMM-20019
- Acronym
- NASH
- Status last verified
- Nov 2021
- First submitted
- 9 May 2016
- Last updated
- 9 Nov 2021
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 9 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A 24-Week, Randomized, Double-blind, Placebo-controlled, Efficacy and Safety Study of 80 mg TEV-45478 Once Daily as Treatment in Adult Patients With Nonalcoholic Steatohepatitis (NASH) Who Also Have Type 2 Diabetes Mellitus - GN
- ClinicalTrials.gov ID
- NCT02769091
- Acronym / sponsor ID
- NASH / TV45478-IMM-20019
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Business decision
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Teva Branded Pharmaceutical Products R&D, Inc.Industry (pharma, biotech, devices)
- Study start
- 30 Sep 2016 (actual)
- Primary completion
- 31 Jan 2018 (estimated)
- Study completion
- 28 Feb 2018 (estimated)
- First posted
- 11 May 2016 (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 assess the effect of TEV-45478, as compared with placebo, on liver health and liver fat content in patients with T2DM who also have Nonalcoholic Steatohepatitis (NASH).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| TEV-45478 | Experimental | Drug: TEV-4547880 mg (2x40mg) tablets once daily for up to 24 weeks |
| Placebo | Placebo comparator | Drug: PlaceboMatching placebo |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- The patient is female or male and aged 18 to 65 years, inclusive with a history of Type 2 Diabetes Mellitus (T2DM) and on stable medication for diabetes or insulin or a combination thereof for at least 3 months prior to screening.
- The patient has a NASH Activity Score (NAS) of ≥4, with or without evidence of fibrosis, with a score of at least 1 in steatosis and lobular inflammation the subcomponents of NAS and a hepatocyte ballooning score of at least 1 score based on historical histological evaluation of liver biopsy within 12 months prior to randomization.
- The patient has a historical diagnosis of NASH, established no more than 12 months prior to randomization based on histology (liver biopsy).
- The patient has an ALT level at screening between 45 and 105 IU/L, inclusive, for women and between 55 and 120 IU/L, inclusive for men, at one other occasion during the 24-weeks prior to screening.
- The patient has an MRI determined liver fat fraction of equal to or higher than 6% at Screening
Key exclusion criteria (17 listed)
- The patient has a history of chronic liver disease other than NASH eg, chronic or acute hepatitis, autoimmune, viral (A, B, C), genetic hepatitis, drug induced hepatotoxicity, Wilson's disease, alcoholic liver diseases, or any other non-NASH active liver disease.
- The patient has active cancer or a history of a malignant disease (except basal cell carcinoma of the skin) within 5 years prior to screening or any history of bladder cancer.
- The patient had an unstable metabolic condition (ie, with a history of weight loss or weight gain of >5 kg within 24 weeks prior to screening)
- The patient has a history of bariatric surgery within 5 years prior to screening.
- The patient has received mercaptopurine or azathioprine previously within 1 year prior to screening
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 |
|---|---|---|
| TEV-4547880 mg (2x40mg) tablets once daily for up to 24 weeks | Drug | TEV-45478 |
| Placebo | Drug | Placebo |
Primary outcome
serum Alanine Transaminase (ALT) levels response, defined as ALT value within reference range of <35 IU/L for women and <40 IU/L for men
Time frame: Week 24
liver fat response, defined as a reduction of ≥6% at week 24 compared to screening by the MRI-Proton Density Fat Fraction (PDFF)
Time frame: Week 24
Percentage of Participants with Adverse Events
Time frame: 24 weeks
7 secondary outcomes
percent change from baseline in ALT
Time frame: Baseline, Week 24
percent change from baseline in ALT
Time frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24 (or early withdrawal)
percent change from baseline in Aspartate Aminotransferase (AST)
Time frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24 (or early withdrawal)
change from baseline in AST
Time frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24 (or early withdrawal)
change from baseline in ALT
Time frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24 (or early withdrawal)
Change from baseline in glycosylated hemoglobin ((HbA1c)
Time frame: Baseline, Weeks 4, 12, and 24 (or early withdrawal)
Change from baseline in liver fibrosis measured using transient elastography (with Fibroscan)
Time frame: Baseline, Week 24 (or early withdrawal)
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Nov 2021.
Related trials for Nonalcoholic Steatohepatitis
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.
Teva Medical Expert, MD study director
Teva Branded Pharmaceutical Products R&D, Inc.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing TEV-45478 in people with Nonalcoholic Steatohepatitis and Type 2 Diabetes Mellitus, run by Teva Branded Pharmaceutical Products R&D, Inc..
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 17 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: withdrawn, as of the sponsor's last update on 9 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. 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?
The study was withdrawn before enrolling participants, so there are no results.
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?
serum Alanine Transaminase (ALT) levels response, defined as ALT value within reference range of <35 IU/L for women and <40 IU/L for men (time frame: Week 24). The study lists 3 primary outcomes in all. 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 9 Nov 2021.