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 |
a long term skin disease characterized by the occurrence of inflamed and
swollen lumps |
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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 | 10020041 |
E.1.2 | Term | Hidradenitis suppurativa |
E.1.2 | System Organ Class | 100000004858 |
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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 demonstrate the efficacy of secukinumab (300 mg q4w or 300 mg q2w) in subjects with moderate to severe HS who were HiSCR responders at Week 52 of the core studies, with respect to loss of response by Week 104, compared to placebo. |
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E.2.2 | Secondary objectives of the trial |
To assess the long-term safety and tolerability of secukinumab in subjects with moderate to severe HS evaluated by adverse events, abnormal laboratory values and vital signs.
To explore time to regain HiSCR response after treatment following loss of response.
To explore the efficacy after uptitration from 300mg q4w to 300mg q2w.
To evaluate the effect of secukinumab as interrupted or continuous treatment
To evaluate the pharmacokinetics of AIN457 at the LOR visit, Exploratory biomarkers at LOR visits
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects eligible for inclusion in this study must meet all of the following criteria:
1. Written informed consent must be obtained before any assessment is performed.
2. Subjects who complete the whole study treatment period (52 weeks) in the core studies (CAIN457M2301 or CAIN457M2302) and have received secukinumab treatment during the Treatment Period 2 of the core studies. |
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E.4 | Principal exclusion criteria |
Subjects meeting any of the following criteria are not eligible for inclusion in this study.
1. A protocol deviation in the core study which, according to the investigator will prevent the meaningful analysis of the extension study for the individual subject.
2. Ongoing or planned use of prohibited HS or non-HS treatments. Time of use of prohibited
treatments in the core study must continue to be adhered to.
3. Subjects not expected to benefit from participation in the extension study, as assessed by
the subject and investigator.
4. Subjects whose participation in the extension study could expose them to an undue safety
risk.
5. Current severe progressive or uncontrolled disease which in the judgment of the
investigator renders the subject unsuitable for the study.
6. Underlying conditions (including, but not limited to metabolic, hematologic, renal, hepatic, pulmonary, neurologic, endocrine, cardiac, infectious or gastrointestinal, such as inflammatory bowel disease), which in the opinion of the investigator significantly immunocompromises the patient and/or places the patient at unacceptable risk for receiving an immunomodulatory therapy.
7. Plans for administration of live vaccines during the study.
8. Women of childbearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using methods of contraception during the entire study or longer if required by locally approved prescribing information (e.g. in European Union
(EU) 20 weeks).
Contraception methods include:
Total abstinence, when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy or bilateral tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment.
Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps). For United Kingdom: with spermicidal foam/gel/film/cream/vaginal suppository.
Use of oral (estrogen and progesterone), injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS). |
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E.5 End points |
E.5.1 | Primary end point(s) |
Time to loss of response up to Week 104 (Randomized Withdrawal period) in subjects who were HiSCR responders at Week 52 in the core studies.
HiSCR response is defined as at least 50% decrease in Abscess and inflammatory Nodule (AN) number relative to the Baseline visit in the core study, with no increase in the number of abscesses and in the number of draining fistulae.
Loss of response is defined as:
1. at least a 50% or greater increase in AN count (abscess and/or nodules) at a regular or unscheduled visit compared to the average AN count from 3 previous visits or the Week 52, whichever is lower, and the increase is at least 3 AN
2. If at a regular or unscheduled visit, the subject experiences at least a 30% increase in AN compared to the average AN count from the 3 previous visits or the Week 52 visit whichever is lower with an increase of at least 2 AN, the subject should be reassessed within 2-4 weeks. A further increase in the
AN count of at least 2 AN would be considered a LOR also.
Note: If the 3 previous visits include visits from core studies, the AN count from the core study will
be included in the average. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Blinded part - HiSCR at 52 weeks of core studies
Primary end point will be assessed at End of Treatment (EOT) -1): Loss of response (LOR) by 104 weeks |
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E.5.2 | Secondary end point(s) |
Adverse events, laboratory values, vital signs.
Time to regain HiSCR response following loss of response
HiSCR, flare, NRS30 after up-titration |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
After LOR has been attained, the subject will receive open label treatment with secukinumab and continue in the study for the maximum duration of 260 weeks of treatment plus 8 weeks of the post-treatment follow-up period in total or, until secukinumab is commercially available for a given trial participant.
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
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 | 5 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 129 |
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 |
Argentina |
Australia |
Austria |
Belgium |
Brazil |
Bulgaria |
Canada |
Colombia |
Croatia |
Czech Republic |
Denmark |
France |
Germany |
Greece |
Guatemala |
Hungary |
India |
Israel |
Italy |
Korea, Democratic People's Republic of |
Lebanon |
Lithuania |
Malaysia |
Mexico |
Netherlands |
Philippines |
Poland |
Portugal |
Russian Federation |
Singapore |
Slovakia |
South Africa |
Spain |
Sweden |
Switzerland |
Taiwan |
Turkey |
United Kingdom |
United States |
Vietnam |
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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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 7 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 7 |