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 |
Hidradenitis Supperativa is a painful, chronic skin disease characterized by recurrent inflamed nodules and abscesses, which may rupture to form fistulas and subsequent scarring |
|
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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020041 |
E.1.2 | Term | Hidradenitis suppurativa |
E.1.2 | System Organ Class | 10040785 - Skin and subcutaneous tissue disorders |
|
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 determine the clinical safety and efficacy of adalimumab compared to placebo in subjects with moderate to severe (HS) |
|
E.2.2 | Secondary objectives of the trial |
To evaluate safety and explore efficacy for continuous weekly dosing versus dose reduction versus maintenance of response off therapy |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Adult subjects must have a diagnosis of HS for at least 1 year (365 days) prior to Baseline;
• HS lesions must be present in at least two distinct anatomic areas, one of which must be at least Hurley Stage II or Hurley Stage III;
• Subject must have stable HS for at least 2 months (60 days) prior to Screening and also at the Baseline visit as determined by the investigator through subject interview and review of medical history;
• Subject must have had an inadequate response to at least a 3-month (90 days) trial of an oral antibiotic for treatment of HS (or demonstrated intolerance to, or have a contraindication to, oral antibiotics for treatment of their HS);
• Subject must have an AN count of greater than or equal to 3 at the Baseline visit;
• Subject has a negative TB screening assessment (including a PPD test and/or Quantiferon-TB Gold test, or equivalent) and negative chest x-ray (CXR) (posterior-anterior [PA] and lateral view) at Screening;
• Subject must agree to daily use (and throughout the entirety of the study) of one of the following over-the-counter topical antiseptics on their HS lesions: chlorhexidine gluconate, triclosan, benzoyl peroxide, or dilute bleach in bathwater;
• Subject is judged to be in good general health, as determined by the Principal Investigator based upon the results of a medical history, physical examination, laboratory profile, CXR and a 12 lead ECG performed during the Screening period and confirmed at Baseline. |
|
E.4 | Principal exclusion criteria |
• Prior treatment with adalimumab or other anti-TNF therapy (e.g., infliximab or etanercept), or participation in an adalimumab trial;
• Subjects on permitted oral antibiotic treatment (doxcycline or minocycline only) for HS who have not been on a stable dose for at least 28 days prior to the Baseline visit;
• Subject received oral concomitant analgesics (including opioids) for HS-related pain within 14 days prior to the Baseline visit;
• If entering the study on concomitant oral analgesics for non-HS-related pain:
• Subject on opioid analgesics within 14 days prior to Baseline visit;
• Subject not on a stable dose of non-opioid oral analgesics for at least 14 days prior to the Baseline visit (PRN is not considered a stable dose).
• Subject requires, or is expected to require, opioid analgesics for any reason (excluding tramadol);
• Subject received prescription topical therapies for the treatment of HS within 14 days prior to the Baseline visit;
• Subject received systemic non-biologic therapies for HS with potential therapeutic impact for HS less than 28 days prior to Baseline visit (other than permitted oral antibiotics);
• Subject has a draining fistula count of greater than 20 at the Baseline visit;
• Infection(s) requiring treatment with intravenous (IV) anti-infectives (antibiotics, antivirals, antifungals) within 30 days prior to Baseline or oral anti-infectives (antibiotics, antivirals, antifungals) within 14 days prior to Baseline, except as required as part of an anti-TB regimen;
• Any other active skin disease or condition (e.g., bacterial, fungal or viral infection) that may interfere with assessment of HS;
• History of demyelinating disease (including myeleitis) or neurologic symptoms suggestive of demyelinating disease;
• History of invasive infection (e.g., listeriosis, histoplasmosis), human immunodeficiency virus (HIV);
• Subject has an active systemic viral infection or any active viral infection that based on the investigator's clinical assessment make the subject an unsuitable candidate for the study;
• Hepatitis B: HBsAg positive (+) or detected sensitivity on the HBV-DNA PCR qualitative test for HBc Ab/HBsAb positive subjects;
• Chronic recurring infections or active TB;
• History of moderate to severe congestive heart failure (NYHA class III or IV), recent cerebrovascular accident and any other condition which, in the opinion of the investigator, would put the subject at risk by participation in the protocol;
• Evidence of dysplasia or history of malignancy (including lymphoma and leukemia) other than a successfully treated non-metastatic cutaneous squamous cell carcinoma, basal cell carcinoma or localized carcinoma in situ of the cervix;
• Pregnant or lactating females. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy variable is the proportion of subjects achieving
HiSCR at Week 12. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
1. Proportion of subjects achieving AN count of 0, 1, or 2 at Week 12, among subjects with Hurley Stage II at Baseline
2. Proportion of subjects achieving at least 30% reduction and at least 1 unit reduction from Baseline in Patient's Global Assessment of Skin Pain (NRS30) – at worst at Week 12 among subjects with baseline NRS ≥ 1
3. Change in modified Sartorius scale from Baseline to Week 12 |
|
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 | Yes |
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 | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
|
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 | 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 | 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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
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 |
Australia |
Canada |
Denmark |
France |
Greece |
Netherlands |
Sweden |
Switzerland |
Turkey |
United States |
|
E.8.7 | Trial has a data monitoring committee | Yes |
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-study is defined as the date of the last subject's last visit or the actual date of follow-up contact, whichever is later. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
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 | 2 |
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 |