A Multi-part, Double Blind Study to Assess Safety, Tolerability and Efficacy of Tropifexor (LJN452) in PBC Patients

NCT02516605 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: CLJN452X22012015-001590-41
• Study Type: interventional
• Target: 61
• Locations: 6 countries
• Sites: 28

Brief Summary

A multi-part study to assess safety, tolerability and efficacy of tropifexor (LJN452) in patients with primary biliary cholangitis

Conditions

Primary Biliary Cholangitis

Keywords

Primary Biliary Cirrhosis, PBC; Primary Biliary Cholangitis

Outcome Measures

Primary Outcomes (7)

• Fold Change in Serum Gamma-glutamyl Transferase (GGT)

  Fold change in serum gamma-glutamyl transferase (GGT) from baseline to Day 28

  Baseline to Day 28

• Blood Pressure

  Vital signs - Systolic Blood pressure

  Screening, Baseline, day 1, day 7, day 14, day 21, day 28, day 56, day 84

• Pulse Rate

  Vital signs

  Screening, Baseline, day 1, day 7, day 14, day 21, day 28, day 56, day 84

• Body Temperature

  Vital signs

  Screening, Baseline, day 1, day 7, day 14, day 21, day 28, day 56, day 84

• ECG - Heart Rate

  Electrocardiogram (ECG)

  Screening, Baseline, day 1, day 28

• ECG Intervals - PR Interval

  Electrocardiogram (ECG)

  Screening, Baseline, day 1, day 28

• Haemoglobin

  Hematology panel for safety laboratory assessments.

  Screening, Baseline, day 1, day 7, day 14, day 21, day 28, day 56, day 84

Secondary Outcomes (6)

• Plasma PK Parameter - AUC 0-8h

  Day 1, Day 28

• Plasma PK Parameter - Cmax

  Day 1, Day 28

• Plasma PK Parameter - Tmax

  Day 1, Day 28

• Changes From Baseline in Total PBC-40 Score

  Baseline, Day 28, Day 56, Day 84

• Change From Baseline in Itch Subdomain of PBC-40 Score

  Baseline, Day 28, Day 56, Day 84

Study Arms (2)

LJN452

EXPERIMENTAL

Drug: Part 1: LJN452; Drug: Part 2: LJN452 Dose level 1; Drug: Part 2: LJN452 Dose level 2

Placebo

PLACEBO COMPARATOR

Drug: Part 1: Placebo; Drug: Part 2: Placebo

Interventions

Part 1: LJN452 DRUG

LJN452 capsules administered once daily for 28 days

Also known as: tropifexor

LJN452

Part 1: Placebo DRUG

Matching placebo capsules administered once daily for 28 days

Placebo

Part 2: LJN452 Dose level 1 DRUG

LJN452 capsules administered once a day for 12 weeks

Also known as: tropifexor

LJN452

Part 2: Placebo DRUG

Matching placebo to LJN452 administered once a day for 12 weeks

Placebo

Part 2: LJN452 Dose level 2 DRUG

LJN452

Also known as: tropifexor

LJN452

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• Diagnosis of PBC as demonstrated by the presence of at least 2 of the following 3 diagnostic criteria:
• History of alkaline phosphatase (ALP) elevated above upper limit of normal (ULN) for at least 6 months
• Positive antimitochondrial antibodies (AMA) titer or if AMA negative or in low titer (\<1:80) PBC specific antibodies (anti-GP210 and/or anti-SP100 and/or antibodies against the major M2 components (PDC-E2, 2-oxo-glutaric acid dehydrogenase complex))
• Previous liver biopsy findings consistent with PBC
• At least 1 of the following markers of disease severity:
• ALP ≥ 1.67 × ULN
• Total bilirubin \> ULN but \< 1.5 × ULN
• In addition, patients must meet the following biochemical criteria at enrollment:
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 5 × ULN
• Total bilirubin ≤ 1.5 × ULN
• INR ≤ ULN
• Taking UDCA for at least 12 months, or for at least 6 months and has reached maximal response to UDCA with a plateau in alkaline phosphatase, with no changes in dose for ≥ 3 months prior to Day 1.
• Patients must weigh at least 40 kg to participate in the study, and must have a body mass index (BMI) within the range of 18 - 40 kg/m2. BMI = Body weight (kg) / \[Height (m)\]2

You may not qualify if:

• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception for 30 days before randomization, during dosing and for 30 days following the end of treatment.
• Presence of other concomitant liver diseases.
• Cirrhosis with complications, including history or presence of:
• Variceal bleed
• Uncontrolled ascites
• Encephalopathy
• Spontaneous bacterial peritonitis
• Significant hepatic impairment as defined by Child-Pugh classification of B or C, history of liver transplantation, current placement on a liver transplant list or current Model for End Stage Liver Disease (MELD) score ≥15.
• History of conditions that may cause increases in ALP (e.g., Paget's disease).
• Use of investigational drugs, or immunosuppressive drugs at the time of enrollment, or within 5 half-lives, or 30 days of randomization, whichever is longer; or longer if required by local regulations. Use of high dose oral steroids to treat co-morbid conditions (e.g., airways disease) will be allowed but must be properly documented as such in concomitant medications.
• Currently taking obeticholic acid or have taken obeticholic acid within 30 days of randomization
• Previous participation in CLJN452X2201 and received study medication within three months of randomization (or longer if required by local regulations).

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (28)

Novartis Investigative Site

Rialto, California, 92377, United States

Location

Novartis Investigative Site

Miami, Florida, 33136, United States

Location

Novartis Investigative Site

Atlanta, Georgia, 30308, United States

Location

Novartis Investigative Site

Marietta, Georgia, 30060, United States

Location

Novartis Investigative Site

Chicago, Illinois, 60612, United States

Location

Novartis Investigative Site

Manhasset, New York, 11030, United States

Location

Novartis Investigative Site

Dallas, Texas, 75390, United States

Location

Novartis Investigative Site

San Antonio, Texas, 78215, United States

Location

Novartis Investigative Site

Seattle, Washington, 98104, United States

Location

Novartis Investigative Site

Calgary, Alberta, T2N 4N1, Canada

Location

Novartis Investigative Site

Edmonton, Alberta, T6G 2B7, Canada

Location

Novartis Investigative Site

Hamburg, 20246, Germany

Location

Novartis Investigative Site

Hanover, 30625, Germany

Location

Novartis Investigative Site

Heidelberg, 69120, Germany

Location

Novartis Investigative Site

München, 81377, Germany

Location

Novartis Investigative Site

Würzburg, 97080, Germany

Location

Novartis Investigative Site

Lodz, 91-347, Poland

Location

Novartis Investigative Site

Mysłowice, 41-400, Poland

Location

Novartis Investigative Site

Warsaw, 02-097, Poland

Location

Novartis Investigative Site

Wroclaw, 50-449, Poland

Location

Novartis Investigative Site

Moscow, 117198, Russia

Location

Novartis Investigative Site

Saint Petersburg, 194044, Russia

Location

Novartis Investigative Site

Samara, 443011, Russia

Location

Novartis Investigative Site

Birmingham, West Midlands, B15 2TH, United Kingdom

Location

Novartis Investigative Site

Cambridge, CB2 2QQ, United Kingdom

Location

Novartis Investigative Site

Hull, HU3 2JZ, United Kingdom

Location

Novartis Investigative Site

London, NW3 2PF, United Kingdom

Location

Novartis Investigative Site

Newcastle upon Tyne, NE1 4LP, United Kingdom

Location

Related Publications (1)

• Schramm C, Wedemeyer H, Mason A, Hirschfield GM, Levy C, Kowdley KV, Milkiewicz P, Janczewska E, Malova ES, Sanni J, Koo P, Chen J, Choudhury S, Klickstein LB, Badman MK, Jones D. Farnesoid X receptor agonist tropifexor attenuates cholestasis in a randomised trial in patients with primary biliary cholangitis. JHEP Rep. 2022 Jul 21;4(11):100544. doi: 10.1016/j.jhepr.2022.100544. eCollection 2022 Nov.

  PMID: 36267872 DERIVED

Related Links

• A Plain Language Trial Summary is available on novartisclinicatrials.com

MeSH Terms

Conditions

Liver Cirrhosis, Biliary

Interventions

tropifexor

Condition Hierarchy (Ancestors)

Cholestasis, Intrahepatic; Cholestasis; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Liver Diseases; Liver Cirrhosis; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 4, 2015
• First Posted: August 6, 2015
• Study Start: September 9, 2015
• Primary Completion: August 2, 2018
• Study Completion: August 2, 2018
• Last Updated: January 5, 2021
• Results First Posted: November 13, 2019

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will share

Locations

GB (5); RU (3); DE (5); CA (2); US (9); PL (4)