| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| MODERATE TO SEVERE GENITAL PSORIASIS |
|
| E.1.1.1 | Medical condition in easily understood language |
| moderate to severe psoriasis in the genital area |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10063407 |
| E.1.2 | Term | Psoriasis genital |
| E.1.2 | System Organ Class | 100000004858 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
The primary objective of the study is to evaluate the clinical efficacy of oral apremilast 30 mg BID,
compared to placebo, in subjects with moderate to severe genital psoriasis during the 16-week Placebo controlled Phase. |
|
| E.2.2 | Secondary objectives of the trial |
The secondary objectives are:
- To evaluate the safety and tolerability of apremilast 30 mg BID, compared with placebo, in subjects with moderate to severe genital psoriasis
- To evaluate the effect of apremilast 30 mg BID compared with placebo on genital psoriasis symptoms
- To evaluate the effect of apremilast 30 mg BID, compared with placebo, on Health-related Quality of Life (HRQoL) |
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Pharmacodynamic Peripheral Blood RNA Gene Expression Analysis Sub-Study:
Type: pharmacodynamics.
Objective of this sub-study is analysis of specific RNAs to define the mechanism of action of apremilast in patient study population. Data may also inform on the subset of patients who are responding well to apremilast treatment.
version and date of protocol final 31 October 2018
Pharmacogenetic Analysis Sub-Study:
Type: pharmacogenetics.
The objective of this sub-study is to analyze the genetic polymorphisms that are associated with clinical and pharmacodynamic interaction with apremilast.
version and date of protocol final 31 October 2018
Inflammatory Plasma Protein Biomarkers Analysis Sub-Study:
Type: other - biomarker assessments.
Objective of this sub-study is to explore the effects of apremilast on concentrations of a select set of interleukins and cytokines and the relationship between biomarker concentrations and clinical efficacy of apremilast.
version and date of protocol final 31 October 2018
Photography Sub-Study:
Type: Other - photography
Photographic assessments will be done at selected sites to provide supportive evidence of apremilast treatment efficacy.
version and date of protocol final 31 October 2018 |
|
| E.3 | Principal inclusion criteria |
Subjects must satisfy the following criteria to be enrolled in the study:
1. Subject is ≥ 18 years of age at the time of signing the informed consent form (ICF).
2. Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
3. Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
4. Subject must have a diagnosis of chronic plaque psoriasis for at least 6 months prior to signing the ICF.
5. Subject must have a diagnosis of moderate or severe psoriasis of the genital area at Screening and Baseline as defined by having a modified sPGA-G score of ≥ 3 (moderate or severe).
6. Subject must have a diagnosis of moderate or severe psoriasis at Screening and Baseline as defined by having a sPGA score of ≥ 3.
7. Subject must have plaque psoriasis (BSA ≥ 1%) in a non-genital area at both Screening and Baseline.
8. Subject must have been inadequately controlled with or intolerant of topical therapy for the treatment of psoriasis affecting the genital area.
9. Subject must be in good health (except for psoriasis) as judged by the investigator, based on medical history, physical examination, clinical laboratories, and urinalysis.
10. Subject must meet the following laboratory criteria:
a. White blood cell count ≥ 3000/mm3 (≥ 3.0 x 109/L) and < 14,000/mm3(< 14 x 109/L)
b. Platelet count ≥ 100,000/μL (≥ 100 x 109/L)
c. Serum creatinine ≤ 1.5 mg/dL (≤ 132.6 μmol/L)
d. Total bilirubin ≤ 2 mg/dL (≤34 μmol/L)
e. Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) ≤ 2 x upper limit of normal (ULN)
11. Females of childbearing potential (FCBP)† must have a negative pregnancy test at Screening and Baseline. While on investigational product and for at least 28 days after taking the last dose of investigational product, FCBP who engage in activity in which conception is possible must use one of the approved contraceptive§ options described below:
Option 1: Any one of the following highly effective methods: hormonal contraception (oral, injection, implant, transdermal patch, vaginal ring); intrauterine device (IUD); tubal ligation; or partner’s vasectomy;
OR
Option 2*: Male or female condom (latex condom or nonlatex condom NOT made out of natural [animal] membrane [for example, polyurethane]; PLUS one additional barrier method: (a) diaphragm with spermicide; (b) cervical cap with spermicide; or (c) contraceptive sponge with spermicide.
A female of childbearing potential is a sexually mature female who
1) has not undergone a hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy (the surgical removal of both ovaries) or
2) has not been postmenopausal for at least 24 consecutive months (that is, has had menses at any time during the preceding 24 consecutive months).
The female subject's chosen form of contraception must be effective by the time the female subject is randomized into the study (for example, hormonal contraception should be initiated at least 28 days before randomization).
* Option 2 may not be an acceptable contraception option in all countries per local guidelines/regulations.
|
|
| E.4 | Principal exclusion criteria |
The presence of any of the following will exclude a subject from enrollment:
1. Subject has any significant medical condition or laboratory abnormality, that would prevent the subject from participating in the study.
2. Subject has any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
3. Subject has any condition that confounds the ability to interpret data from the study.
4. Subject is pregnant or breast feeding.
5. Subject has positive Hepatitis B surface antigen or anti-hepatitis C antibody at Screening.
6. Subject has active tuberculosis (TB) or a history of incompletely treated TB.
7. Subject has history of positive human immunodeficiency virus (HIV), or has congenital or acquired immunodeficiency (eg, common variable immunodeficiency disease).
8. Subject has active substance abuse or a history of substance abuse within 6 months prior to Screening.
9. Subject has bacterial infections requiring treatment with oral or injectable antibiotics, or significant viral or fungal infections, within 4 weeks of Screening. Any treatment for such infections must have been completed at least 4 weeks prior to Screening.
10. Subject has malignancy or history of malignancy (except for treated [i.e. cured] basal cell or squamous cell in situ skin carcinomas and treated [i.e. cured] cervical intraepithelial neoplasia [CIN] or carcinoma in situ of the cervix with no evidence of recurrence).
11. Subject has prior history of suicide attempt at any time in the subject’s life time prior to signing the informed consent and randomization, or major psychiatric illness requiring hospitalization within the last 3 years prior to signing the informed consent.
12. Subject has psoriasis flare/rebound (defined as a sudden worsening of body psoriasis or psoriasis of the genitalia which requires administration of prohibited medications) within 4 weeks of Screening or between the Screening and Baseline Visit.
13. Subject has current or planned concurrent use of the following therapies that may have a possible effect on psoriasis of the body and/or genital area during the course of the treatment phase of the trial:
a. Topical therapy within 2 weeks prior to randomization (including but not limited to topical corticosteroids, vitamin D analog preparations, calcineurin inhibitors).
-Exceptions: unmedicated emollients (eg, Eucerin®) for body and genital lesions and non-medicated shampoos for scalp lesions (Subjects should not use these topical treatments within 24 hours prior
to the clinic visit.)
b. Conventional systemic therapy for psoriasis within 4 weeks prior to randomization (including but not limited to cyclosporine, corticosteroids, methotrexate, oral retinoids, mycophenolate, thioguanine, hydroxyurea, sirolimus, sulfasalazine, azathioprine, fumaric acid esters).
c. Phototherapy treatment of body within 4 weeks prior to randomization (i.e. ultraviolet B [UVB], psoralen and ultraviolet A radiation [PUVA]).
d. Biologic therapy:
i. TNF or IL-17 blockers such as adalimumab, brodalumab, certolizumab pegol, etanercept, infliximab, ixekizumab, secukinumab (or biosimilars for each) within 12 weeks prior to randomization
ii. Anti-IL-12 or anti-IL-23 monoclonal antibodies such as ustekinumab, guselkumab, or tildrakizumab, within 24 weeks prior to randomization
e. Use of any investigational drug beginning 4 weeks prior to randomization, or 5 pharmacokinetic/pharmacodynamic half-lives, if known (whichever is longer).
14. Subject has evidence of skin conditions that would interfere with clinical assessments.
15. Subject has prolonged sun exposure or use of tanning booths or other ultraviolet (UV) light sources.
16. Subject had prior treatment with apremilast.
17. Subject has history of allergy or hypersensitivity to any components of the IP. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Static Physician Global Assessment of Genitalia (sPGA-G) 0/1 (modified): Proportion of subjects with a
modified sPGA-G score of clear (0) or almost clear (1) with at least a 2-point reduction from baseline |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
- Static PGA (sPGA) 0/1: Proportion of subjects achieving an overall sPGA score of clear (0) or almost
clear (1) with at least a 2-point reduction from baseline
- Genital Psoriasis Itch Numeric Rating Scale (GPI-NRS): Proportion of subjects with at least a 4-point improvement in GPI-NRS item score within the Genital Psoriasis Symptoms Scale (GPSS) for subjects with a baseline score of ≥ 4
- Body Surface Area (BSA): Change from baseline in affected BSA
- Dermatology Life Quality Index (DLQI): Change from baseline in DLQI total score
- Genital Psoriasis Symptoms Scale (GPSS): Change from baseline in GPSS total score and individual items scores |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 21 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Canada |
| United States |
| Belgium |
| France |
| Germany |
| Italy |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The End of Trial is defined as either the date of the last visit of the last subject to complete the
post-treatment follow-up, or the date of receipt of the last data point from the last subject that is
required for primary, secondary and/or exploratory analysis, as prespecified in the protocol,
whichever is the later date. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 4 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 4 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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