Phase II study to assess the safety and efficacy of LNPP1955 in patients with psoriasis
- Conditions
- Moderate to severe plaque psoriasisMedDRA version: 20.0Level: LLTClassification code 10071117Term: Plaque psoriasisSystem Organ Class: 100000018190Therapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]
- Registration Number
- EUCTR2016-001531-12-HU
- Lead Sponsor
- upin Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 40
Patients will be enrolled in the Main part and MTX Add-on part of the
study only if they meet all of the following criteria:
1. Male or female ambulatory patients aged 18 to 75 years (both
inclusive) diagnosed with moderate-to-severe chronic stable plaque
psoriasis with active disease, PASI score of = 10 and affected BSA =
10% and willing to provide informed consent;
2. Plaque psoriasis for at least 6 months prior to first dose of IP;
3. Are a candidate for phototherapy, photochemotherapy, or systemic
therapy of plaque psoriasis (either naive or history of previous
treatment);
4. Have not taken biologics within 6 months prior to administration of IP
in this study;
5. Have not received systemic non-biologic psoriasis therapy (including,
but not limited to, retinoids or vitamin D analogs, cyclophosphamide,
cyclosporine, fumaric acid esters, pimecrolimus, or psoralen plus
ultraviolet A light [PUVA]) or phototherapy within 4 weeks before the
first dose of IP;
6. Have not received topical psoriasis treatment within 2 weeks before
the first dose of IP;
7. Sexually active women of childbearing potential and men must be
willing to use a reliable means of contraception (e.g. combined or
progestogen only hormonal contraception, intrauterine devices [IUDs],
surgical sterilization, double barrier, or vasectomized partner) during
participation in this study and at least 2 months after the last dose of the
IP OR postmenopausal women (aged greater than 45 years) with a
history of amenorrhea for at least 1 year from the time of last menstrual
cycle and have follicle-stimulating hormone (FSH) value indicating
menopause with high reliability. Additional Inclusion Criteria for Main
part: 1. Have not received MTX within 6 weeks prior to first dose of IP.
Additional Inclusion Criteria for MTX Add-on part:
1. MTX naive and eligible to receive 7.5 mg MTX per week after having
tolerated at least one dose (OR);
2. Patients receiving stable dose of 7.5 mg MTX per week.
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 24
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 8
Patients who meet any of the following criteria will not be eligible for the
study:
1. Current diagnosis of non-plaque forms of psoriasis, e.g.,
erythrodermic, guttate, or pustular psoriasis;
2. Known allergies or hypersensitivities that can have potential impact
on patient's participation as determined by the Investigator;
3. Receiving drugs that are known to exacerbate psoriasis such as beta
blockers, calcium channel blockers, antimalarial drugs or lithium;
4. Receiving oral or injectable (e.g., intraarticular, intramuscular, or
intravenous) corticosteroids for any other condition;
5. Women who are pregnant, lactating, or planning pregnancy while
enrolled in the study and at least 2 months after last dose of the IP; 6.
History of infection requiring hospitalization, parenteral antimicrobial
therapy, or
otherwise judged clinically significant by the Investigator within 1
month prior to first dose of IP;
7. History of infection requiring oral antimicrobial therapy within 2
weeks prior to first dose of IP;
8. Patients with active tuberculosis, prior history of unsuccessfully
treated tuberculosis (TB), latent TB (patients who are positive for test
for latent TB e.g. QuantiFERON®-TB Gold test or appropriate test), or
those who are at risk of developing TB;
9. History of any lymphoproliferative disorder (such as Epstein Barr
Virus [EBV] - related lymphoproliferative disorder), history of
lymphoma, leukemia, or signs and symptoms suggestive of current
lymphatic disease;
10. Patients suffering from significant acute or chronic, localized or
disseminated infections (bacterial/fungal/viral) or sepsis, or patients
with a history of recurring infections except Herpes simplex within 3
months prior to screening, or those who are at an increased risk of
developing infections or sepsis as determined by the Investigator;
11. History or presence of any immunological disease or use of
immunosuppressive or any therapy within a period that can have a 12. Recent live vaccine administration within 4 weeks prior to screening
and during the study;
13. Have any known condition affecting oral absorption of drug e.g.,
(malabsorption syndrome), or not able to swallow IP for any reason;
14. History of abuse of alcohol, recreational, or illegal drugs within 1
year prior to screening;
15. Tested seropositive for Hepatitis B [Hepatitis B surface antigen
(HBsAg)], and Hepatitis C virus (HCV), or human immunodeficiency virus
(HIV);
16. History of malignancy in the last five years prior to screening, except
curatively treated basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) of the skin;
17. Severe anemia (hemoglobin < 8 g/dL), leukopenia or thrombocytopenia (white blood cell [WBC] < 3,500/µL; platelet count < 100,000/µL), biochemistry (aspartate aminotransferase [AST] or alanine aminotransferase [ALT] > 3x upper limit of normal [ULN]; serum creatinine > 1.5 mg/dL (133 µmol/L) up to age 65 years and > ULN if age > 65 years) and serum bilirubin > 2 x ULN;
18. Significant abnormalities in the ECG;
19. Current or recent history of a severe, progressive, or uncontrolled
disease or any clinically significant laboratory abnormality, which in the
opinion of investigator makes the patient inappropriate for inclusion in
this study.
Additional Exclusion Criteria for MTX Add-on part:
1. Intolerance to MTX;
2. Contraindication to MTX (e.g., hypersensitivity to MTX or its
excipients, blood
dyscrasias etc.);
3. Receiving medicines with antifolate activity (e.g., co-trimox
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objectives of the study are as follows:<br>• To assess the POE of LNP1955 and find an optimum dose in patients<br>with moderate-to-severe plaque psoriasis;Secondary Objective: The secondary objectives of the study are as follows:<br>• To assess the PD and safety of LNP1955 in comparison to placebo;<br>• To explore the pharmacokinetics (PK) of LNP1955 and synergy with<br>MTX in patients with moderate-to-severe plaque psoriasis in an open label study arm.;Primary end point(s): The proportion of patients achieving at least 75% reduction (PASI 75) from baseline in Psoriasis Area and Severity Index (PASI) after 12 weeks of treatment.;Timepoint(s) of evaluation of this end point: 12 weeks from baseline
- Secondary Outcome Measures
Name Time Method Secondary end point(s): The proportion of patients achieving at least 75% reduction (PASI 75)<br>from baseline in PASI after 4 and 8 weeks of treatment;<br>• The proportion of patients achieving at least 50% reduction (PASI 50)<br>from baseline in PASI after 4, 8, and 12 weeks of treatment;<br>• The proportion of patients achieving at least 90% reduction (PASI 90)<br>from baseline in PASI after 4, 8, and 12 weeks of treatment;<br>• Improvement in Physician's Global Assessment (PGA) in psoriasis<br>severity scores from baseline at 4, 8, and 12 weeks of treatment.;Timepoint(s) of evaluation of this end point: 4 and 8 weeks from baseline for PASI 75<br>4,8 and 12 weeks from baseline for PASI 50, PASI 90 and PGA