Evaluate long-term safety, tolerability and efficacy of adalimumab in subjects with moderate to severe hidradenitis suppurativa.
ID
Source
Brief title
Condition
- Skin and subcutaneous tissue disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The following efficacy variables will be determined throughout the study to
evaluate the long-term efficacy of adalimumab to treat moderate to severe HS:
HiSCR
Abcess count
Draining fistula count
Non-draining fistula count
Inflammatory nodule count
Non-inflammatory nodule count
Hypertrophic scar count
AN-count
Modified Sartorius-score
erythema
Hurley Stage at eacht affected anatomic region
Patient global assessment of skin pain
DLQI
WPAI:SHP
TSQM
Secondary outcome
N/A
Background summary
HS is a painful, chronic, skin disease characterized by recurrent inflamed
nodules and abscesses, which may rupture to form fistulas and subsequent
scarring. The most commonly involved anatomic locations are the inguino-crural
and axillary folds, with sub-mammary folds (in women) and the perineal area
less commonly involved.
Hidradenitis Suppurativa has a severely negative effect on patients' quality of
life. It typically presents with painful, deep-seated nodules, which either
resolve spontaneously, persist as non-tender nodules, or progress to form
abscesses. Abscesses typically rupture and release purulent drainage. Abscesses
and nodules may heal with scarring and the formation of fistulas or sinus
tracts. Thus, many patients with HS develop permanent sequelae of past
inflammation that are only remediable through surgical excision of the involved
skin areas. The physical and psycho-social morbidity associated with en bloc
excision of scarred axillary, inguinal, or groin skin is substantial. Rare
complications of HS include fistula formation into urethra, bladder, rectum, or
peritoneum, lymphedema of the limbs or scrotal elephantiasis, and squamous cell
carcinomas of the skin originating from HS lesions.
Hidradenitis Suppurativa affects approximately 1% of the general population.
Disease onset is typically after puberty. Disease prevalence decreases from
1.5% in those < 25 years of age to 0.5% in those older than 55 years of age. It
affects women from 2 to 5 times more commonly than men. Several factors may
predispose a person to HS, including genetics, cigarette smoking, and obesity.
The histopathologic characteristics of HS include a dense inflammatory cell
infiltrate of neutrophils, lymphocytes, and histiocytes. Tumor necrosis
factor-alpha (TNF-*), which induces pro-inflammatory cytokines and activates
neutrophils and lymphocytes, may have a pathogenic role.
Study objective
Evaluate long-term safety, tolerability and efficacy of adalimumab in subjects
with moderate to severe hidradenitis suppurativa.
Study design
All subjects who participated in the phase-3 studys M11-810 (performed in The
Netherlands) and M11-313 (not performed in The Netherlands) can participate in
this open-label extension study, provided that the investigator considers the
subject suitable as a candidate for the follow-up study, and the subject did
not develop any exclusion criteria during the study.
Intervention
Starting at baseline, all subjects will receive open-label adalimumab 40mg per
week, regardless of treatment assignment in the prior phase-3 study. If at any
time on or after week 24 of the open-label extension a subject meets the
following criteria, the dosing regimen may be reduced to adalimumab 40mg every
other week:
- Achieves HiSCR (Hidradenitis Suppurativa Clinical Response) response during
the OLE relative to baseline visit of the prior phase-3 study, AND;
- Achieves an AN count of 0 or 1 on at least 2 consecutive study visits, AND;
- The physician and subject mutually decide that the risk/benefit of reducing
adalimumab dosing to every other week is favorable.
Study burden and risks
During the study, all subject will visit the hospital approximately 11 times.
This is dependent on how long they will stay in the study (see remark in this
form question E11). Furthermore the subject has to return to the hospital 4 and
8 weeks after the last study medication dose (if the subject discontinues
adalimumab, and does not continue on commercially available adalimumab) for
PK-sampling. Subject will be contacted telephonically 70 days after last study
drug dosing for safety follow-up. ECG and X-thorax will only be repeated during
baseline if, in the opinion of the investigator, clinically significant AEs
develop, that warrants a repeat. A PPD test will be done during the week-12
visit. This will be annually repeated until the subject discontinues the study
drug. A physical exam will be done at each visit.
In total, blood will be drawn at approximately 11 visits (3,5-21 ml). The
drawing of blood may cause fainting, infections of the vein, pain, bruises and
infections. Also, a bleeding can occur at the injection site. Several
questionnaires will need to be completed. One will be completed at all visits,
the other three at four visits. Subjects need to bring a urine sample to
approximately 9 visits. Women of childbearing potential will take a urine
sample to all visits. The following adverse events may occur when the subject
uses the study medication: The most frequent adverse events of adalimumab are
the injection site reactions. Subjects can have redness, itching, bruising pain
and/or swelling of the injection site. Most reactions are considered mild or
moderate, and most reactions disappeared without stopping the treatment with
adalimumab. The following adverse events have been reported frequently: upper
respiratory tract infection, headache, skin rash, sinusitis, bronchitis,
nausea, diarrhea, abdominal pain, joint pain, backpain, urinary tract
infections, hypertension and influenza. Women of fertile age have to use a
reliable method of contraception as described in the protocol. The use of some
medication is not allowed during the study (Page 31-32, section 5.2.3.3
Protocol version 30 November 2011)
Wegalaan 9
Hoofddorp 2132 JD
NL
Wegalaan 9
Hoofddorp 2132 JD
NL
Listed location countries
Age
Inclusion criteria
1) Subjects who previously participated in a prior Phase3 HS study (M11-810) and:
* completed the study, or
* achieved HiSCR at the entry of period B, then experienced a loss of response (LOR) defined as an AN count that is greater than the average of AN counts at baseline and week 12 of the prior Phase 3 HS study; or
* did not achieve HiSCR at the entry of period B, then experienced worsening or absence of improvement on or after week 16 of the prior phase 3 HS study, defined as an AN count * Baseline AN count at two consecutive visits (excluding week 12) occurring * 14 days apart
2) If female, subject is either:
* Not of childbearing potential, defined as postmenopausal for at least 1 year (365 days); or
* Surgically sterile (bilateral tubal ligation, bilateral oophorectomy and/or hysterectomy; or
* Of childbearing potential and is practicing an approved method of birth control throughout the study and for 150 days after last dose of study drug.
3) Subject must agree to daily use (throughout the entirety of the study) of one of the following over-the-counter topical antiseptics on their body areas affected with HS lesions: chlorhexidine gluconate, triclosan, benzoyl peroxide, or dilute bleach in bathwater.
Exclusion criteria
1. Prior treatment with any other anti-TNF therapy (e.g., infliximab, etanercept), or participation in an adalimumab trial other than a prior Phase 3 HS study.
2. Any other active skin disease or condition (e.g., bacterial, fungal or viral infection) that may interfere with assessment of hidradenitis suppurativa.
3. Subject received any oral antibiotic treatment for HS within 28 days prior to the Baseline visit of Study M12-555, except for antibiotics permitted in a prior Phase 3 HS study.
4. Subject received prescription topical therapies for the treatment of HS within 14 days prior to the Baseline visit of Study M12-555.
5. Subject received systemic non-biologic therapies with potential therapeutic impact for HS < 28 days prior to Baseline visit of Study M12-555.
6. Subject received oral concomitant analgesics (including opioids) for HS-related pain within 14 days prior to the Baseline visit of Study M12-555, except for permitted analgesics taken in the prior Phase 3 HS study.
7. Subject has been treated with any investigational drug of chemical or biologic nature within a minimum of 30 days or 5 half-lives (whichever is longer) of the drug prior to the Baseline visit other than investigational drug taken in a prior Phase 3 HS study.
8. Prior exposure to natalizumab (Tysabri®) or efalizumab (Raptiva®).
9. Infection(s) requiring treatment with intravenous (IV) anti-infectives (antibiotics, antivirals, antifungals) within 30 days prior to the Baseline visit of Study M12-555 or oral anti-infectives (antibiotics, antivirals, antifungals) within 14 days prior to the Baseline visit of Study M12-555, except as required as part of an anti-TB regimen or as permitted in a prior Phase 3 HS study.
10. History of moderate to severe congestive heart failure (New York Health Association [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.
11. History of demyelinating disease (including myelitis) or neurologic symptoms suggestive of demyelinating disease.
12. History of invasive infection (e.g., listeriosis, histoplasmosis), human immunodeficiency virus (HIV).
13. Subject has an active systemic viral infection or any active viral infection that based on the investigator's clinical assessment makes the subject an unsuitable candidate for the study.
14. Chronic recurring infections or active TB.
15. Known hypersensitivity to adalimumab or its excipients as stated in Section 5.5.2, Table 3.
16. Positive pregnancy test at Baseline.
17. Female subjects who are breast-feeding or considering becoming pregnant during the study.
18. 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.
19. History of clinically significant drug or alcohol abuse in the last 12 months (365 days).
20. Clinically significant abnormal laboratory results as evaluated by the investigator.
21. Subject is considered by the investigator for any reason, to be an unsuitable candidate for the study and not able to comply with the study protocol.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2011-003478-98-NL |
| CCMO | NL39105.018.12 |