| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Moderate-to-Severe Plaque Psoriasis |
| умерен до тежък плакатен псориазис |
|
| E.1.1.1 | Medical condition in easily understood language |
| Moderate-to-Severe Plaque Psoriasis |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
| 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 | 10071117 |
| E.1.2 | Term | Plaque psoriasis |
| 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 |
• Evaluate the efficacy of oral piclidenoson 2 mg or 3 mg twice daily (BID) in patients with moderate-to-severe plaque psoriasis, compared with placebo, as determined by the proportion of subjects who achieve a Psoriasis Area and Severity Index (PASI) score response of ≥75% (PASI 75) at Week 16 (superiority); and
• Evaluate the safety of oral piclidenoson in this patient population. |
|
| E.2.2 | Secondary objectives of the trial |
• Evaluate the efficacy of oral piclidenoson 2 mg or 3 mg BID, compared with placebo, as determined by the proportion of subjects who achieve, respectively, PASI 50, PGA score of 0 or 1, and improvement on the PDI at Week 16 (superiority)
• Evaluate the efficacy of oral piclidenoson 2 mg or 3 mg BID, compared with apremilast, as determined by the proportion of subjects who achieve PASI 75, PGA score of 0 or 1, PASI 50 (non-inferiority), and improvement in PDI at Weeks 16 and 32;
• Establish assay sensitivity within this trial by comparing the efficacy of apremilast 30 mg BID with that of placebo tablets BID, as determined by the proportion of subjects who achieve PASI 75, PGA score of 0 or 1, PASI 50, and improvement in PDI at Week 16(superiority);
• Determine PK of piclidenoson under the circumstances of this trial using sparse sampling; and
• Evaluate the relationship between pre-treatment whole blood A3AR expression levels and response to piclidenoson treatment.
|
|
| 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 |
Optional Body Surface Photography Sub-Study
|
|
| E.3 | Principal inclusion criteria |
1. Male or female, 18 to 80 years of age, inclusive;
2. Diagnosis of moderate-to-severe chronic plaque-type psoriasis with
BSA involvement ≥10%, as judged by the Investigator;
3. PASI score ≥12 (Appendix 3);
4. Static PGA ≥3 (Appendix 2);
5. Candidate for systemic treatment or phototherapy for psoriasis;
6. Duration of psoriasis of at least 6 months;
7. Females of childbearing potential must have a negative serum
pregnancy test at screening;
8. Female subjects of childbearing potential must use highly effective
contraception throughout the course of the trial and for 3 months after.
Highly effective methods include hormonal contraception (e.g.,
combined oral contraceptives, patch, vaginal ring, injectables, and
implants; each method must be used with a barrier method, preferably
male condom), intrauterine device or system, tubal ligation, partner
vasectomy, or dual (male plus female) barrier methods (each barrier
method must be used with a hormonal method).
Female subjects who use a hormonally based method must agree to use
it in conjunction with a barrier method. Female partners of male study
subjects should consider using one of the above methods of
contraception as well. Post-menopausal status is defined as menopause
for at least 1 year prior to the Screening Visit and must be confirmed by
an elevated serum FSH level.
9. Male subjects must refrain from sperm donation during treatment and
until at least 90 days after the end of study drug dosing. Male subjects
with fertile or pregnant partners must agree to use condoms throughout
the course of the trial and for 3 months after.
10. Ability to complete the study in compliance with the protocol; and
11. Ability to understand and provide written informed consent. |
|
| E.4 | Principal exclusion criteria |
1. Psoriasis limited to erythrodermic, guttate, palmar, plantar, or
generalized pustular psoriasis in the absence of plaque psoriasis;
2. Prior treatment with apremilast within 4 weeks prior to the Baseline
visit, or
contraindication to apremilast;
3. Treatment with systemic retinoids, corticosteroids, tofacitinib, or
immunosuppressive agents (e.g., methotrexate, cyclosporine) within 4
weeks of the Baseline visit;
4. Treatment with a biological agent (etanercept, adalimumab,
efalizumab, infliximab, ustekinumab, alefacept, secukinumab, or others,
including investigational agents) within a period of time equal to 5 times
its circulating half-life, or 30 days, whichever is longer, prior to the
Baseline visit;
5. Treatment with high potency topical dermatological corticosteroids
(Class I-III in US, Class III-IV in Europe), Vitamin D analogs,
keratolytics, or coal tar (other than on the scalp, palms, groin, and/or
soles) within 2 weeks of the Baseline visit;
6. Ultraviolet or Dead Sea therapy within 4 weeks of the Baseline visit, or
anticipated need for either of these therapies during the study period;
7. Treatment with lithium, hydroxychloroquine or chloroquine within 2
weeks of the Baseline visit, or anticipated need for such drugs during the
study period, unless dose has been stable for 3 months prior to the
Screening visit and will remain stable throughout the trial;
8. Serum creatinine level greater than 1.25 times the laboratory's upper
limit of normal atScreening;
9. Liver aminotransferase levels greater than 1.5 times the laboratory's
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upper limit of normal at Screening;
10. QTcF interval on Screening Visit ECG or on average of triplicate
Baseline Visit ECGs >450 milliseconds (msec) for males or > 470 msec
for females (except when QT prolongation is associated with right or left
bundle branch block, in which case enrollment is allowed);
11. A condition which increases proarrhythmic risk, including
hypokalemia, hypomagnesemia, or congenital Long QT Syndrome;
12. Heart disease which is, in the Investigator's judgment, clinically
unstable;
13. Ongoing or planned use of a concomitant medication that is on the
CredibleMedsTM list of drugs known to cause Torsades des Pointes
(Appendix 7);
14. Active gastrointestinal disease which could interfere with the
absorption of oral medication;
15. Pregnancy, planned pregnancy, lactation, or inadequate
contraception as judged by the Investigator;
16. Active drug or alcohol dependence;
17. History of depression or suicidal ideation within the past year;
18. Concomitant use of strong cytochrome P450 inducers, e.g., rifampin,
phenobarbital, phenytoin, carbamazepine;
19. Previous participation in a piclidenoson (CF101) clinical trial, defined
as having received at least one dose of study medication;
20. Significant acute or chronic medical or psychiatric illness that, in the
judgment of the Investigator, could compromise subject safety, limit the
subject's ability to complete the study, and/or compromise the
objectives of the study;
21. Participation in another investigational drug or vaccine trial
concurrently or within 30 days prior to the Screening visit. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| •Proportion of subjects achieving PASI 75 |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| •Endpoint evaluated at Week 16 |
|
| E.5.2 | Secondary end point(s) |
•Proportion of subjects achieving PASI 75 Week 32 and PASI 50 at Weeks 16 and 32
•Proportion of subjects achieving PGA of 0 or 1 at Weeks 16 and 32
• Change From Baseline (CFB) in PDI at Weeks 16 and 32 |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
•Endpoint evaluated at Week 32 - Proportion of subjects achieving PASI 75
•Endpoint evaluated at at Weeks 16 and 32 - Proportion of subjects achieving PASI 50
•Endpoint evaluated at Weeks 16 and 32 - Proportion of subjects achieving PGA of 0 or 1
•Endpoint evaluated at at Weeks 16 and 32 - Change From Baseline (CFB) in PDI |
|
| 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 | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| 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) | Yes |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 4 |
| 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 | 6 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 19 |
| 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 |
| Israel |
| Poland |
| Bulgaria |
| Romania |
| Bosnia and Herzegovina |
| Croatia |
| Moldova, Republic of |
| Serbia |
|
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 1 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 1 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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