| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| inflammatory and hyperproliferative skin condition |
|
| E.1.1.1 | Medical condition in easily understood language |
| inflammatory skin condition |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
| MedDRA Classification |
| 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 |
| To evaluate the efficacy of three concentrations of topical bimiralisib as compared to matching vehicle and two approved topical medications (Daivobet® and Daivonex®) applied once daily to distinct 2 cm diameter treatment mini-zones on each patient. |
|
| E.2.2 | Secondary objectives of the trial |
1) To evaluate the overall safety and local tolerability of topical bimiralisib.
2) To evaluate additional efficacy parameters. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Male or female patient aged 18 years or above having signed and dated an informed consent.
2. Phototype I to IV on Fitzpatrick’s scale (7).
3. Patients who are women of childbearing potential must agree to use a highly effective method of contraception from screening until 30 days after the last dose of bimiralisib.
4. Female of non-child bearing potential, defined as surgically sterile or post-menopausal (at least two years post cessation of menses).
5. Female of childbearing potential having a negative blood pregnancy test at screening and a negative urine pregnancy test at baseline.
6. Male patients with female partners who are of childbearing potential must agree to refrain from attempting to father children by using a condom for up to 30 days after the last dose of bimiralisib and should inform their partner about the risk of embryo-fetal toxicity.
7. Patient must be otherwise healthy, i.e. absence of clinically significant or unstable disease, with acceptable organ function with laboratory values within normal range as specified below:
a. eGFR (mCockcroft-Gault) > 30 mL/min
b. AST and ALT <= 2.5x ULN
c. Total bilirubin <= 1.5x ULN (except patients with Gilbert’s syndrome, who may have total bilirubin <= 3x ULN)
d. Platelet count >= 100’000 /mm3
e. WBC count >= 3’000 /mm3
f. ANC count >= 3’000 /mm3
g. Fasting blood glucose <= 150 mg/dL
8. Patient with a diagnosis of mild to moderate plaque psoriasis with lesions located on arms and/or legs and/or trunk.
9. Target plaques and treatment mini-zones must fulfill the following criteria (as assessed by the investigator):
a. Target plaques must be located on the upper and lower extremities (apex of elbows, knees and shin areas excluded) and/or trunk.
b. Treatment mini-zones must be placed on stable psoriasis plaques (target plaques) based on Total Plaque Score (TPS)* evaluated at screening visit and at baseline visit (TPS variation of +/-1 grade)
* The Total Plaque Score is defined as the Total Clinical Score (TCS) calculated for each Target Plaque selected at screening.
c. The TCS of each treatment mini-zone must be 6 to 9 inclusive at baseline visit, with each individual item ≥ 2 (erythema, scaling and infiltration).
d. All treatment mini-zones must be of similar severity at baseline (identical TCS or +/-1 grade).
10. Patient willing and able to follow all the study procedures and complete the whole study
11. Patient affiliated to a social security system (according to French law). |
|
| E.4 | Principal exclusion criteria |
1. Patient with current diagnosis of guttate, erythrodermic, exfoliative or pustular psoriasis.
2. Female patient who is pregnant or who is breast feeding.
3. Patient not accepting blood sampling.
4. Patient receiving systemic treatment with biological therapies (marketed or not marketed) with a possible effect on plaque psoriasis
a. within twenty-four (24) weeks prior to randomization and during the study for alefacept, briakinumab, efalizumab or ustekinumab.
b. within twelve (12) weeks prior to randomization and during the study for other biological immunomodulating agents (e.g. adalimumab, abatacept, brodalumab, certolizumab, gilimumab, etanercept, infliximab, ixekizumab, secukinumab).
5. Patient receiving any non-biological systemic treatments, with a potential effect on plaque psoriasis (e.g., corticosteroids, retinoids, immunosuppressants) within four (4) weeks prior to randomization.
6. Patient using any potent or very potent (WHO group III-IV) topical corticosteroids within four (4) weeks prior to randomization.
7. Patient using phototherapy within four (4) weeks prior to randomization.
8. Patient using topical drugs for the treatment of psoriasis within two (2) weeks prior to randomization such as:
- Topical retinoids (e.g. tazarotene),
- Topical vitamin D analogues (e.g. calcipotriol),
- Topical immunomodulators (e.g. macrolides),
- WHO group I-II corticosteroids (except on facial psoriasis),
9. Patient using emollients on the selected plaques within one (1) week before randomization and during the study.
10. Patient with initiation of, or expected changes to concomitant medication that may affect psoriasis vulgaris (e.g., beta blockers, anti-malaria drugs, lithium and ACE inhibitors) within 2 weeks prior to randomization and during the study.
11. Patient with current hypercalcemia or past history of hypercalcemia, vitamin D toxicity.
12. History of any severe disease or serious current condition (based on patient interview and/or results of screening physical examination and safety laboratory assessments) which, in the opinion of the investigator, would put the patient at risk by participating in the study or would interfere significantly with the evaluation of study results or the study course (e.g. cancer, severe cardiopathy, severe renal insufficiency, severe hepatic insufficiency).
13. For all patients: a known history of positive serology for Hepatitis B, Hepatitis C, or HIV.
14. For patients consenting to skin biopsies: positive serology (HbsAg, anti-HCV, anti-HIV 1 or 2) (blood sampling done at screening visit).
15. Patient who has received treatment with any non-marketed drug substance within the 4-week period or five (5) half-lives whichever is longer prior to randomization.
16. Patient with current participation in any other interventional clinical trial.
17. Patient with known or suspected hypersensitivity to any component(s) of the study drugs.
18. Patient with any concomitant medical or dermatological disorder(s) which might preclude accurate evaluation of the psoriasis on the treatment mini-zones.
19. Patient foreseeing an intensive solar exposure during the study (UV radiation, etc.) or having been exposed within two weeks preceding the screening visit.
20. Patient impossible to contact in case of emergency.
21. In the opinion of the investigator, patient who is unlikely to comply with the study protocol (e.g. alcoholism, drug dependency or psychotic state).
22. Patient who is in an exclusion period in the National Biomedical Research Register of the French Ministry of Health at randomization.
23. Patient under legal supervision or guardianship, hospitalized in a public or private institution, for a reason other than the research or subject deprived of freedom.
24. Only for patients consenting to skin biopsies: patients presenting any of the following criteria contraindicating skin biopsies can participate in the study, but no biopsies can be taken:
- Known allergy to local anesthetics,
- Past or current history of coagulation trouble
- Past or current history of abnormal healing (hypertrophic scars, pitted or sunken scars, dyschromic scars),
- History or physical evidence of keloids or hypertrophic scarring resulting from skin trauma,
- Patient with treatments which may impair hemostasis (anticoagulant, antiplatelets, etc…) in the month preceding the biopsy and/or during the clinical trial. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Area Under the Effect Curve (AUEC) of Total Clinical Score (TCS)* from Day 1 to Day 29.
*defined as the sum of psoriasis severity index scores of erythema, scaling and induration
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Psoriasis severity index scores for erythema, scaling and induration will be recorded at screening and twice weekly during the treatment period from Day 1 (before treatment application) to Day 29. |
|
| E.5.2 | Secondary end point(s) |
Safety endpoints
- (Serious) Adverse Events
- Local tolerability measured by Local Irritation Grading Scale for each treatment mini-zone
- Changes in physical examination parameters
- Changes in vital signs
- Changes in safety laboratory parameters
Efficacy endpoints
- Success rate (defined as a Physician Global Assessment clearing score of 0 or 1) at each evaluation visit and the time to first success on all mini-zones;
- AUEC of individual clinical scores (erythema, scaling and induration) from Day 1 to Day 29;
- Total clinical score (TCS) and percentage change from baseline at each visit on all mini-zones;
- Erythema, scaling and induration scores and their changes from baseline at each visit on all mini-zones;
- Skin thickness and poor echographic band thickness at Day 1 and Day 29.
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| From Day 1 (before treatment application) to Day 29. |
|
| 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 | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| 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) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | Yes |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
| single-center, investigator-blinded, within-patient randomized, controlled trial |
|
| 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 | 6 |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| 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
|
| Last visit of the last subject (LVLS) |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | 4 |
| E.8.9.1 | In the Member State concerned days | |
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