E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
|
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 | 10000519 |
E.1.2 | Term | Acne vulgaris |
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 objectives of this study are to determine a) the adrenal suppression potential and b) the trough plasma concentrations associated with topical application of CB-03-01 cream, 1% in subjects with acne vulgaris. |
|
E.2.2 | Secondary objectives of the trial |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subject is male or female, 9 to <12 years of age at the time of consent/assent.
2. Subject must provide written informed assent and be accompanied by the parent or legal guardian at the time of assent/consent signing. The parent or legal guardian must provide written informed consent for the subject.
3. Females of childbearing potential1 must be using highly effective birth control methods2,3 with a negative urine pregnancy test (UPT) at the Screening and Baseline Visits.
4. Subject has moderate to severe facial acne vulgaris (Grade 3 or 4) as determined by the Investigator’s Global Assessment (IGA) [0 (clear) to 4 (severe) scale] and obvious acne on the trunk (i.e., shoulders, upper chest, and/or back) at the Screening Visit.
5. Subject has facial acne vulgaris with a minimum of 15 inflammatory lesions (papules, pustules, and nodules/cysts) and a minimum of 15 non-inflammatory lesions (open and closed comedones) at the Screening Visit.
6. Subject must be in general good health in the opinion of the investigator, with normal renal function as defined per protocol4 and no clinically relevant abnormalities present at the screening physical examination, in the subject’s medical history, or from safety laboratory tests (hematology, serum chemistry, and urinalysis).
7. Subject has normal adrenal function measured with a Cosyntropin Stimulation Test (CST) at Screening, defined as a normal pre-stimulation cortisol level and a 30-minute post-stimulation cortisol level of >18 μg/dL.
8. Subject and parent/guardian are able to communicate with the staff and are willing to comply with study instructions, reside at and/or return to the clinic for required visits. |
|
E.4 | Principal exclusion criteria |
1. Subject is pregnant, lactating, or is planning to become pregnant during the study.
2. Subject has a Body Mass Index (BMI) for age percentile >95% .
3. Except for the use of contraceptives, subject reported use of any prescription drug or herbal product within two (2) weeks of Visit 2 (Baseline), any non-prescription drug or vitamin or mineral supplements within one (1) week of Visit 2 (Baseline); any known enzyme-inducer,enzyme-inhibitor, or reported chronic exposure to enzyme-inducers such as paint solvents or pesticides within 30 days of Visit 2 (Baseline).
4. Subject has used topical anti-acne medications containing retinoids such as tazarotene, adapalene, or tretinoin within four (4) weeks of Visit 2 (Baseline).
5. Subject has used the following systemic anti-acne medications: antibiotics within two (2) weeks of Visit 2 (Baseline), spironolactone within four (4) weeks of Visit 2 (Baseline), or retinoid therapy within three (3) months of Visit 2 (Baseline).
6. Subject has used topical corticosteroids (including inhaled and intranasal corticosteroids) within two (2) weeks of the CST at Visit 1 (Screening) and/or between Visit 1 (Screening) CST and Visit 2 (Baseline).
7. Subject has used systemic corticosteroids (including intramuscular and intralesional injections) within four (4) weeks of the CST at Visit 1 (Screening) and/or between the Visit 1 (Screening) CST and Visit 2 (Baseline).
8. Subject has used light treatments, microdermabrasion or chemical peels to the face, chest, and/or back within eight (8) weeks of Visit 2 (Baseline).
9. Subject has any skin or medical condition, including facial hair that could interfere with the evaluation of the test article or requires the use of interfering topical or systemic therapy.
10. Subject has any condition which, in the investigator’s opinion, would make it unsafe for the subject to participate in this research study.
11. Subject has the need or plans to be exposed to artificial tanning devices or excessive sunlight during the study.
12. Subject cannot avoid any type of strenuous exercise (swimming, running, team sports, etc.) or the use of hot tubs/saunas from Visit 2 (Baseline) to the end of the study (Visit 4).
13. Subject has any clinically significant medical abnormality or chronic disease of the cardiovascular, gastrointestinal, respiratory, hepatic, or renal systems. This includes conditions (e.g., gastrointestinal surgery) that may interfere with metabolism or excretion.
14. Subject has a history of alcohol and/or drug abuse in the investigator's judgment or has a positive urine drug screen result at Visit 1 (Screening).
15. Subject is unable to communicate or cooperate with the investigator due to language problems, poor mental development, or impaired cerebral function.
16. Subject is known to be hypersensitive to the test article or any components in the test article (see Section 6.1).
17. Subject has received an investigational drug or been treated with an investigational device within 30 days prior to Visit 2 (Baseline).
18. Subject is currently enrolled in an investigational drug or device study.
19. Subject has an irregular sleep schedule (cortisol levels exhibit physiological diurnal variation) as judged by the investigator.
20. Subject has experienced significant blood loss, as judged by the investigator, within 60 days or has donated plasma within 72 hours prior to Visit 2 (Baseline).
21. Subject tests positive at screening for human immunodeficiency virus (HIV) or is known to be seropositive for HIV.
22. Subject tests positive at Visit 1 (Screening) for hepatitis B surface antigen, hepatitis C antibody, or has a history of a positive result.
23. Subject had major surgery within 30 days prior to Visit 2 (Baseline) or plans to have surgery during the study.
24. Subject has participated in a prior CB-03-01 clinical trial. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Hypothalamic-Pituitary-Adrenal (HPA) Axis Response to Cosyntropin: Measurement of serum cortisol concentrations after stimulation of the adrenal cortex with Cosyntropin (CST) at Screening and Day 14 (or EOS). HPA axis suppression is defined as a post-stimulation serum cortisol level <18 μg/dL at Day 14 (or EOS).
• Trough Plasma Concentrations: Trough measurements of cortexolone 17α-propionate and cortexolone concentration in plasma at Screening, Baseline, Day 7 and Day 14. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Screening, baseline, Day 7 and Day 14 |
|
E.5.2 | Secondary end point(s) |
- Safety laboratory testing (hematology, clinical chemistry, and urinalysis) at Screening and Day 14 (or EOS).
- Local and systemic AEs at every visit (Baseline, Days 7 and 14).
The severity of the following LSRs [for face and trunk, separately]: telangiectasia, skin atrophy, striae rubrae, erythema, edema, scaling/dryness, stinging/burning, and pruritus at Baseline (pre- and post-test article application), Day 7, and Day 14.
- Physical examination/vital signs at Screening and Day 14 (or EOS).
- UPTs (for all females of childbearing potential) at Screening, Baseline, and Day 14 (or EOS).
- ECG at Screening and Day 14 (or EOS). |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Screening, baseline, Day 7 and Day 14 |
|
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 | No |
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) | 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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
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 | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 8 |
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 |
|
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
|
LVLS or otherwise decide by the sponsor or investigator. |
|
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 | 0 |
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 |