Study in patients with plaque psoriasis with coexisting non-alcoholic fatty liver disease
- Conditions
- plaque psoriasis with coexisting non-alcoholic fatty liver diseaseMedDRA version: 20.0Level: LLTClassification code 10071117Term: Plaque psoriasisSystem Organ Class: 100000004858MedDRA version: 22.0Level: LLTClassification code 10029530Term: Non-alcoholic fatty liverSystem Organ Class: 100000004871Therapeutic area: Body processes [G] - Immune system processes [G12]
- Registration Number
- EUCTR2019-003168-37-DE
- Lead Sponsor
- ovartis Pharma GmbH
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 90
1. Patient must be able to understand and communicate with the investigator and comply with the requirements of the study, and must provide written, signed and dated informed consent before any study assessment is performed.
2. Men and women = 18 years of age at the time of consent.
3. Moderate to severe plaque-type psoriasis diagnosed for at least 6 months prior to Screening with a PASI of >10 at baseline.
4. Candidate for systemic therapy, defined as a subject having moderate to severe chronic plaque-type psoriasis that is inadequately controlled by:
• topical treatment and/or,
• Phototherapy and/or,
• Previous systemic therapy.
5. Diagnosis of NAFLD by either ultrasound at Screening or liver histology within 6 months before Baseline.
6. Obesity with BMI > 25 kg/m2 at Screening.
7. Elevation of ALT 1.2 to 3.0 × ULN.
8. Liver fat = 8% at Screening as determined by the reading of the central MRI vendor of locally produced images. Note: the MRI assessment should only be performed after eligibility has been confirmed for all other Screening assessments.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 80
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10
1. Forms of psoriasis other than chronic plaque-type psoriasis at Screening.
2. Drug-induced psoriasis at Screening and baseline.
3. Ongoing use of prohibited treatments. Respective washout periods detailed in this section have to be adhered to.
4. History of hypersensitivity to any of the study drug constituents.
5. Pregnant or nursing (lactating) women.
6. Women of childbearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during the study or longer if required by locally approved prescribing information.
7. Previous treatment with biological drug targeting IL-17 or the IL-17 receptor.
8. Past medical history record of infection with HIV, hepatitis B or hepatitis C prior to screening.
9. Active systemic infections during the last two weeks (exception: common cold) prior to randomization or any infection that reoccurs on a regular basis.
10. History of an ongoing, chronic or recurrent infectious disease, or evidence of tuberculosis infection as defined by a positive QuantiFERON TB-Gold Plus (QFT) test at screening. Subjects with a positive or indeterminate QFT test may participate in the study if full tuberculosis work up (according to local practice/guidelines) was completed within 12 weeks prior to randomization and establishes conclusively that the subject has no evidence of active tuberculosis. If presence of latent tuberculosis is established, then treatment according to local guidelines must have been completed prior to screening. During treatment of latent tuberculosis, ALT had to remain below 2x compared to pre-treatment ALT value.
11. Significant medical problems, including but not limited to:
• Congestive heart failure [New York Heart Association status of class III or IV].
• Severely reduced kidney function (eGFR = 29 mL/min/1.73 m2).
12. Unstable weight (± 5%) over the last 6 months prior to Screening.
13. Type I diabetes, or uncontrolled Type II diabetes defined as HbAlc = 10% at Screening.
14. Total white blood cell (WBC) count < 2500/µL, or neutrophils < 1500/µL or hemoglobin < 8.5 g/dL at Screening.
15. Evidence of hepatic decompensation or severe liver impairment or cirrhosis, as defined by the presence of any of the following abnormalities:
• Serum albumin < 3.2 mg/dL
• INR > 1.3
• Total bilirubin > 1.3 mg/dL
• AST > 5 × ULN
• Alkaline phosphatase > 300 IU/L
• Platelets outside of normal reference range (± 5%)
• History of esophageal varices, ascites, or hepatic encephalopathy
• Splenomegaly
16. History of liver transplantation or planned liver transplant.
17. History of biliary diversion.
18. Presence or history of other liver disease (including but not limited to autoimmune hepatitis, hereditary hemochromatosis, alpha 1-antitrypsin deficiency, Wilson’s disease, drug-induced liver disease).
19. 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 or more than 30 g/day in males, on average) or a score on the modified AUDIT questionnaire = 8.
20. History of bariatric surgery or intention to have bariatric surgery during study conduct.
Other protocol-defined exclusion criteria may apply.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To demonstrate superiority of secukinumab compared to placebo in patients with moderate to severe chronic plaque-type psoriasis and NAFLD with respect to PASI90 response at Week 12.;Secondary Objective: • To evaluate the effect of secukinumab compared to placebo on hepatic inflammation in patients with moderate to severe psoriasis and NAFLD with respect to serum ALT levels at Week 12.<br>• To evaluate the effect of secukinumab in patients with moderate to severe psoriasis and NAFLD compared to placebo on quality of life with respect to DLQI at Week 12.<br>;Primary end point(s): Proportion of patients achieving PASI90 response at Week 12.;Timepoint(s) of evaluation of this end point: Week 12
- Secondary Outcome Measures
Name Time Method Secondary end point(s): • Serum ALT level at Week 12.<br>• Proportion of patients achieving DLQI 0/1 at Week 12.<br>;Timepoint(s) of evaluation of this end point: Week 12