Primary objectiveTo assess the efficacy of tildrakizumab treatment (as assessed by PASI 75) in moderate-to-severe plaque psoriasis patients who are non-responders to DMF. Secondary objectivesTildrakizumab- To assess the efficacy of tildrakizumab…
ID
Source
Brief title
Condition
- Epidermal and dermal conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary Endpoint (Part 2)
Proportion of patients who were non-responders to DMF at Week 16 that were
treated with Tildrakizumab and achieved a PASI 75 at week 40.
Secondary outcome
Secondary endpoints (Part 1 and Part 2):
Efficacy endpoints (Part 1)
- Proportion of patients achieving PASI 50, PASI 75 and PASI 90 responses at
Week 8 and Week 16 Visits of the Part 1
- Proportion of patients achieving absolute PASI scores of <=5, <=3 and <=1 at
Week 8 and Week 16 Visits of the Part 1
- Absolute PASI score and change in the absolute PASI score at Week 8 and Week
16 Visits of the Part 1
- Absolute BSA score and change from baseline in the absolute BSA score at Week
8 and Week 16 Visits of the Part 1
- Proportion of patients achieving PGA, ScPGA* and PPPGA* scores of 0 or 1 at
Week 8 and Week 16 Visits of the Part 1
- Absolute PGA, ScPGA* and PPPGA* scores and change in the absolute PGA, ScPGA*
and PPPGA* scores at Week 8 and Week 16 Visits of the Part 1
- Proportion of patients achieving DLQI scores of 0 or 1 at Week 8 and Week 16
Visits of the Part 1
- Absolute DLQI score and change from baseline in the absolute DLQI score at
Week 8 and Week 16 Visits of the Part 1
- Absolute Skindex-16 score and change from baseline in the absolute Skindex-16
score at Week 8 and Week 16 Visits of the Part 1
- Absolute pruritus-VAS score and change from baseline in the absolute
pruritus-VAS score at Week 8 and Week 16 Visits of the Part 1
- Absolute MOS score and change from baseline in the absolute MOS score at Week
16 Visit of the Part 1
Efficacy endpoints (Part 2)
- Proportion of patients achieving PASI 50, PASI 75, PASI 90, and PASI 100
responses at each visit of the Part 2.
- Proportion of patients achieving absolute PASI scores of <=5, <=3 and <=1 at
each visit of the Part 2
- Absolute PASI score and absolute and percentage change from baseline in the
absolute PASI score at each visit of the Part 2
- Absolute BSA score and change from baseline in the absolute BSA score at each
visit of the Part 2
- Proportion of patients achieving PGA, ScPGA* and PPPGA* scores of 0 or 1 at
each visit of the Part 2
- Absolute PGA, ScPGA* and PPPGA* scores and absolute and percentage change
from baseline in the absolute PGA, ScPGA* and PPPGA* scores at each visit of
the Part 2Proportion of patients achieving DLQI score of 0 or 1 at Week 32 and
Week 40 Visits of the Part 2
- Absolute DLQI score and absolute and percentage change from baseline in the
absolute DLQI score at Week 32 and Week 40 Visits of the Part 2
- Absolute Skindex-16 score and absolute and percentage change from baseline in
the absolute Skindex-16 score at Week 32 and Week 40 Visits of the Part 2
- Absolute pruritus-VAS score and absolute and percentage change from baseline
in the absolute pruritus-VAS score at each visit of the Part 2
- Absolute MOS score and absolute and percentage change from baseline in the
absolute MOS score at Week 40 Visit of the Part 2
* Only in patients with scalp involvement
* Only in patients with palmar or plantar involvement
Safety endpoints
- Safety and tolerability as assessed by vital signs, physical examination,
safety laboratory and Treatment-Emergent Adverse Events (TEAEs)
Other Endpoints
- Proportion of patients withdrawing from the trial at each visit and overall,
as well as time to withdrawal
- Treatment compliance
- Proportion of patients using TCS at each visit and overall, as well as
duration of TCS treatment
Background summary
Dimethyl fumarate (DMF) and Tildrakizumab have both been approved in the
European Union as systemic treatments for adult patients with
moderate-to-severe plaque psoriasis in need of systemic therapy. There is no
data available on the efficacy, safety and tolerability of tildrakizumab in
patients who are non-responders to DMF.
Study objective
Primary objective
To assess the efficacy of tildrakizumab treatment (as assessed by PASI 75) in
moderate-to-severe plaque psoriasis patients who are non-responders to DMF.
Secondary objectives
Tildrakizumab
- To assess the efficacy of tildrakizumab treatment (as assessed by PASI, BSA,
PGA, scalp PGA and palmoplantar PGA) in moderate-to-severe plaque psoriasis
patients who are non-responders to DMF.
- To assess the efficacy of tildrakizumab treatment according to Patient
Reported Outcome (PRO) results (DLQI, Skindex-16, pruritus-VAS and MOSS) in
moderate-to-severe plaque psoriasis patients who are non-responders to DMF.
- To assess the safety and tolerability of tildrakizumab treatment in
moderate-to-severe plaque psoriasis patients who are non-responders to DMF.
Dimethyl Fumarate
- To assess the efficacy of DMF treatment (as assessed by PASI, BSA, PGA, scalp
PGA and palmoplantar PGA) in moderate-to-severe plaque psoriasis patients.
- To assess the efficacy of DMF treatment according to PRO results (DLQI,
Skindex-16, pruritus-VAS and MOSS) in moderate-to-severe plaque psoriasis
patients.
- To explore patient*s adherence rate to DMF treatment in moderate-to-severe
plaque psoriasis patients
- To assess the safety and tolerability of DMF treatment in moderate-to-severe
plaque psoriasis patients
Study design
This is a multicentre, randomized, parallel group, open label phase IV clinical
study in patients with moderate-to-severe chronic plaque psoriasis.
The study consists of two parts. Part 1 will include one Screening Period Visit
and the first 16 weeks of the Treatment Period (seven visits: two virtual
visits and five on-site visits). Virtual visit are visits in which patients do
not assist to the centre, but still Investigators should enter data in the
electronic Case Report Form (eCRF) based on the medical record or the
information that patients have entered in the Study App. During Part 1 of the
study all participants receive DMF.
Non-responders continue in Part 2 of the study and will recieve tildrakizumab.
Part 2 will include the last 24 weeks of the Treatment Period (three additional
visits) and a virtual Safety Follow-up Visit,. For patients who have received
only DMF the Safety Follow-up Visit will take place 4 weeks after the last DMF
dose, while for patients who have received tildrakizumab this visit will take
place 17 weeks after the last tildrakizumab dose (i.e. 5 half-lives).
Intervention
Eligible patients will receive DMF standard scheme from Baseline to Week 16
(Part 1 of the study). The DMF standard scheme will follow the guidance of the
SmPC posology. As such, in the first week, patients should take DMF 30 mg once
daily (one tablet in the evening). In the second week, patients should take DMF
30 mg twice daily (one tablet in the morning and one in the evening). In the
third week, patients should take DMF 30 mg three times daily (one tablet in the
morning, one at midday, and one in the evening). In the fourth week, treatment
should be switched to only one tablet of DMF 120 mg in the evening. Patients
should then increase the dose of DMF by one 120 mg tablet per week at different
times of day for the subsequent 5 weeks. The maximum daily dose taken by a
patient should be 720 mg (3 x 2 tablets of DMF 120 mg).
Non-responders will continue in Part 2 of the study and receive tildrakinumab..
The dose of tildrakizumab will be 100 mg (as per the SmPC), and will be
administered as subcutaneously (SC) injection at Weeks 16, 20 and 32. In
patients with certain characteristics (e.g. high disease burden, body weight >=
90 kg) 200 mg may provide greater efficacy. Investigators will be allowed to
prescribe either of the two doses depending on the individual patient*s
characteristics at the beginning of the Part 2. Once a dose is chosen and
treatment with tildrakizumab is initiated, dose changes (e.g. from 100mg to
200mg or vice versa) will not be allowed
Study burden and risks
The amount and number of blood samples: 7 times, total amount for the entire
study is 50ml.
The number of site visits can either be 8 (incl. 2 virtual visits) for Part 1
of the study or 12, for Parts 1 and 2
Physical examinations incl vital signs:2 (Part 1) or 3 times (Parts 1 and 2)
Blood and urine tests, Questionnaires on health and skin, Pregnancy test
(urine, except one blood test at screening): 6 (Part 1) or 9 times (Parts 1 and
2).
Photographs of skin lesions (for 50 subjects total, and only if separate
consent is given): 2 (Part 1) or 3 times (Parts 1 and 2)
Risks associated with the investigational products are described under E9.
Hogeweg 35-h
Zaltbommel 5301 LJ
NL
Hogeweg 35-h
Zaltbommel 5301 LJ
NL
Listed location countries
Age
Inclusion criteria
1. Ability to understand and comply with the requirements of the study and
communicate with the Investigator, and written, signed and dated informed
consent given before any study related activity is performed.
2. Male or female, aged 18 years at the time of the Screening Visit.
3. Diagnosed with chronic plaque psoriasis of at least 6 months prior to the
Screening Visit, and has stable active plaque-type psoriasis (stable is defined
as without clinically significant flares during the 12 weeks before the
Baseline Visit).
4. Moderate-to-severe plaque psoriasis at the Screening and Baseline visits as
defined by PASI score of >= 10
5. Complete record of at least the last 12 months prior to the Screening Visit
of anti-psoriatic previous topical, phototherapy and non-biologic systemic
treatments, if any.
6. Candidate for systemic treatment for plaque psoriasis at the Screening Visit
7. General good health, or a stable medical condition not considered likely to
interfere with the conduct of the clinical study, as determined by the
Investigator based upon results of medical history, laboratory results (within
normal or clinically acceptable range limits) and physical examination (no
clinical significant abnormal findings). Investigators are encouraged to
consult with the Sponsor if there are questions regarding the significance of
any out of range values.
8. Unlikely to conceive, as indicated by at least one *yes* answer to the
following questions:
a. Patient is a male.
b. Patient is a surgically sterilized female by hysterectomy or bilateral tubal
ligation.
c. Patient is a postmenopausal female >=45 years of age with >1 year since last
menses. If a patient is <45 years of age, or cessation of menses is more than 3
months and less than 1 year, follicle stimulating hormone must be documented as
elevated into the postmenopausal range (>60 mIU/mL) at the Screening visit.
d. Patient is a non-sterilized and pre-menopausal female using a highly
effective medically accepted method of contraception, during the study period
and for 4 or 17 weeks after the last dose of DMF or tildrakizumab respectively.
Explanatory note: Highly effective methods of birth control are defined as a
method with less than 1% failure rate (e.g. hormone implants, hormone
injections, some intrauterine devices, vasectomized partner or sexual
abstinence) or the use of two methods of contraception (e.g. one barrier method
[condom, diaphragm or cervical/vault caps] with spermicide and one hormonal
contraceptive [e.g. combined oral contraceptives, patch, vaginal ring,
injectables and implants])
9. For female patients of child-bearing potential, a negative serum pregnancy
test at the Screening Visit and a negative urine pregnancy test at the Baseline
Visit. Additionally, they must agree to have urine pregnancy tests while on
study medication.
Exclusion criteria
1. Female patients who are currently pregnant, who intend to become pregnant
during the course of the study, or who are breastfeeding. Also if there is
unwillingness/inability for the patients (women or men) to use appropriate
measures of contraception (if necessary).
2. Current forms of psoriasis other than chronic plaque-type (e.g.
erythrodermic, guttate, or pustular psoriasis)
3. Drug-induced psoriasis (i.e., a new onset or current exacerbation of
psoriasis from beta-blockers, calcium channel blockers, or lithium) at the
Screening Visit
4. History or evidence of skin disease (atopic dermatitis, eczema) or
conditions (scarring, open wounds) other than chronic plaque-type psoriasis
that might interfere with the study conduct or evaluations, or which exposes
the patient to unacceptable risk by study participation
5. History of hypersensitivity or allergy to the study drugs or its
excipients,which includes lactose*.
*People with rare hereditary problems of galactose intolerance, the Lapp
lactase deficiency or
glucose-galactose malabsorption should not be included in the study.
6. History of or concurrent malignancy (excluding successfully treated basal
cell carcinoma, squamous cell carcinoma of the skin in situ, squamous cell
carcinoma with no evidence of recurrence within 5 years or carcinoma in situ of
the cervix that has been adequately treated).
7. History of or current relevant autoimmune diseases (e.g. lupus-like
syndromes) other than psoriasis.
8. Active significant gastrointestinal problems (ulcers, diarrhoea, etc.) at
the Screening Visit
9. Severe renal impairment (creatinine clearance <30 mL/min, estimated
glomerular filtration rate [eGFR] using CKD-EPI Creatinine Equation) or
significant proteinuria (3+ or higher measured by dipstick) at the Screening
Visit.
10. Any of the following haematological abnormality at the Screening Visit:
a. Platelet count < 100,000/mm3
b. White blood cell count < 3,000 cells/mm3,
c. Lymphocyte count <1.000/µl,
d. Haemoglobin, haematocrit, or red blood cell count outside 30 % of the upper
or lower limits of normal for the laboratory
11. Abnormal liver enzymes at the Screening Visit:
a. If an enzyme was >3x the upper limit of the normal range (ULN): aspartate
amino transferase (AST; serum glutamic oxaloacetic transaminase [SGOT]),
alanine amino transferase (ALT; serum glutamic pyruvic transaminase [SGPT]),
gamma-glutamyl-transferase (GGT), alkaline phosphatase (ALP)
b. If bilirubin was >2x ULN, for the other liver enzymes >2x ULN was
exclusionary
12. Active infectious disease at the Screening Visit
13. Known positive test for human immunodeficiency virus or any other
immunosuppressive disease
14. Known latent or active tuberculosis (TB) at the Screening visit
15. History (within 2 years prior to the Screening Visit) or
evidence/indication of current drug and/or alcohol abuse or dependence,
according to the judgment of the Investigator
16. Previous exposure to fumarate-based drug or a biologic systemic treatment
(e.g. tumour necrosis factor-alpha inhibitors, IL-17 inhibitors, IL-17R
inhibitors, IL-12/23 p40 inhibitors, IL-23p19 inhibitors or experimental
biological product)
17 Have had a live vaccination within 4 weeks prior to the Baseline Visit, or
intend to have a live vaccination during the course of the study, or have
participated in a vaccine clinical study within 12 weeks of the Baseline Visit
18 Patient who intend to use any concomitant medication not permitted by this
study or who have not undergone the required washout period, prior to the
Baseline Visit, for a particular prohibited medication:
a. Topical psoriasis treatment (e.g. topical corticosteroids, vitamin A
analogues, vitamin D analogues, coal tar, anthracene derivatives, salicylic
acid preparations): 2 weeks
b. Phototherapy (e.g. UV-B light phototherapy, Psoralen-UVA therapy, tanning
salon or home-administered UVB): 4 weeks
c. Conventional systemic anti-psoriatic drugs (e.g. cyclosporine, methotrexate,
apremilast or acitretin) excluding fumarate-based drugs: 4 weeks
d. Any other immunosuppressive medication (e.g. cytostatics, etc.): 6 months
19. Concomitant treatment with immunomodulating or systemic corticosteroid.
20. Participating in a drug investigational trial within the 30 days (or five
half-lives, whichever is longer) prior to enrolment.
21. Concurrent systemic therapy with drugs that may interfere with the study
drugs taken within the defined washout period
22. Previously included in the current study
23. Patient who is employee at the research site or Almirall
24. Patient with any other serious or uncontrolled physical or mental
dysfunction that, as judged by the Investigator, could place the patient at
higher risk derived from his/her participation in the study, could confound the
results of the study or is likely to prevent the patient from complying with
the requirements of the study or completing the study.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2019-000817-35-NL |
| CCMO | NL69610.091.19 |