Upadacitinib for Hidradenitis Suppurativa
(Step-Up HS Trial)
Recruiting in Palo Alto (17 mi)
+317 other locations
Age: Any Age
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: AbbVie
Must be taking: Anti-TNF biologics
Must not be taking: Cell-depleting therapies
Disqualifiers: Active skin disease, Investigational drugs, others
Pivotal Trial (Near Approval)
Prior Safety Data
Approved in 3 Jurisdictions
Trial Summary
What is the purpose of this trial?
This trial is testing if a daily pill called upadacitinib can help people with a painful skin condition called hidradenitis suppurativa (HS) who haven't responded to usual treatments. The study will involve adults and teenagers and will check for safety and effectiveness over time. Participants will be randomly given either the medication or a non-active pill, and their progress will be monitored through periodic medical check-ups.
Will I have to stop taking my current medications?
The trial requires stopping certain medications before starting. You must stop using prescription topical therapies for HS and systemic antibiotics at least 14 days before the trial begins. Other investigational drugs and certain cell-depleting therapies must also be stopped before participating.
How is the drug Upadacitinib unique for treating hidradenitis suppurativa?
Eligibility Criteria
Adults and adolescents with moderate to severe Hidradenitis Suppurativa (HS) who haven't improved on anti-TNF therapy can join. They must have HS in at least two areas, been diagnosed for over 6 months, and meet specific lesion counts. Excluded are those with other active skin diseases or recent use of certain drugs.Inclusion Criteria
My skin condition affects at least one area and is moderate to severe.
I have tried at least one TNF inhibitor for HS for 12 weeks or a non-TNF biologic for 16 weeks without success, or I couldn't tolerate it.
I have HS lesions in at least two different body areas.
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Exclusion Criteria
I have no active skin conditions or infections that could affect my HS assessment.
I haven't had cell-depleting therapies like rituximab in the last year or until my B cell count normalized.
I haven't taken antibiotics for HS or any chronic inflammation in the last 14 days.
See 2 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment Period 1
Participants receive oral tablets of upadacitinib or placebo once daily
16 weeks
Regular outpatient visits
Treatment Period 2
Participants continue treatment based on response in Period 1
20 weeks
Regular outpatient visits
Long-Term Extension
Eligible participants continue to receive upadacitinib or placebo
68 weeks
Regular outpatient visits
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Treatment Details
Interventions
- Upadacitinib (Janus Kinase (JAK) Inhibitor)
Trial OverviewThe trial tests Upadacitinib's effectiveness against HS compared to a placebo. It's double-blinded, so participants won't know if they're getting the drug or placebo. The study has three periods: initial treatment phase, adjustment based on results, and long-term extension for up to 68 weeks.
Participant Groups
9Treatment groups
Experimental Treatment
Placebo Group
Group I: Period 3: Long-Term ExtensionExperimental Treatment2 Interventions
Eligible participants will continue to receive upadacitinib or placebo for 68 weeks. Participants will be followed-up for approximately 30 days.
Group II: Period 2: Group 6 - PlaceboExperimental Treatment1 Intervention
Participants who were randomized to upadacitinib Dose A in Period 1 who achieve HiSCR 50 (CR) at Week 16 will receive placebo once daily for 20 weeks.
Group III: Period 2: Group 5 - Upadacitinib Dose BExperimental Treatment1 Intervention
Participants who were randomized to upadacitinib Dose A in Period 1 who achieve HiSCR 50 (CR) at Week 16 will receive upadacitinib Dose B once daily for 20 weeks.
Group IV: Period 2: Group 4 - Upadacitinib Dose AExperimental Treatment1 Intervention
Participants who were randomized to upadacitinib Dose A in Period 1 who achieve HiSCR 50 (CR) at Week 16 will receive upadacitinib Dose A once daily for 20 weeks.
Group V: Period 2: Group 3 - Upadacitinib Dose AExperimental Treatment1 Intervention
Participants who were randomized to upadacitinib Dose A in Period 1 who did not achieve HiSCR 50 (CNR) at Week 16 will continue to receive upadacitinib Dose A once daily for 20 weeks.
Group VI: Period 2: Group 1 - Upadacitinib Dose AExperimental Treatment1 Intervention
Participants who were randomized to placebo in Period 1 who did not achieve HiSCR 50 (clinical non-responder, CNR) at Week 16 will receive Upadacitinib Dose A once daily for 20 weeks.
Group VII: Period 1: Upadacitinib Dose AExperimental Treatment1 Intervention
Participants will receive Upadicitinib Dose A once daily for 16 weeks.
Group VIII: Period 1: PlaceboPlacebo Group1 Intervention
Participants will receive Placebo once daily for 16 weeks.
Group IX: Period 2: Group 2 - PlaceboPlacebo Group1 Intervention
Participants who were randomized to placebo in Period 1 who achieve HiSCR 50 (clinical responder, CR) at Week 16 will continue to receive placebo once daily for 20 weeks.
Upadacitinib is already approved in European Union, United States, Canada for the following indications:
🇪🇺 Approved in European Union as Rinvoq for:
- Rheumatoid arthritis
- Psoriatic arthritis
- Atopic dermatitis
- Ankylosing spondylitis
- Ulcerative colitis
- Crohn's disease
🇺🇸 Approved in United States as Rinvoq for:
- Rheumatoid arthritis
- Psoriatic arthritis
- Atopic dermatitis
- Ankylosing spondylitis
- Ulcerative colitis
- Crohn's disease
🇨🇦 Approved in Canada as Rinvoq for:
- Rheumatoid arthritis
- Psoriatic arthritis
- Atopic dermatitis
- Ankylosing spondylitis
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Research Toronto /ID# 255273Toronto, Canada
UMass Memorial Medical Center /ID# 258839Worcester, MA
Skin Care Research Boca Raton /ID# 253814Boca Raton, FL
Karma Clinical Trials /ID# 254120St. John's, Canada
More Trial Locations
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Who Is Running the Clinical Trial?
AbbVieLead Sponsor
References
Off-Label Use of Janus Kinase Inhibitors in Inflammatory Cutaneous Diseases. [2023]Dysregulation of Janus kinase (JAK) pathways from uncontrolled cytokine signaling comprises the pathological basis for many complex inflammatory cutaneous disorders. Oral JAK inhibitors, upadacitinib, tofacitinib, and baricitinib targeting JAK 1 and JAK 1/3, respectively, are currently US Food and Drug Administration (FDA)-approved for several rheumatic conditions. However, studies have shown that JAK-mediated signaling pathways are involved in many immune-related dermatologic conditions. As a result, for recalcitrant diseases, JAK inhibitors are potential alternative therapies due to their broad targeted inhibitory mechanisms. In this case series, we present the successful off-label treatment of 6 cases across dermatomyositis, hidradenitis suppurativa, cutaneous lupus, and cutaneous Crohn’s disease, which failed conventional therapies with upadacitinib or tofacitinib. In the 3 dermatomyositis cases, use of upadacitinib or tofacitinib demonstrated positive clinical outcomes, with no recurrent symptoms in cases where upadacitinib was used. In treatment-resistant hidradenitis suppurativa, upadacitinib demonstrated reduced systemic flares and moderate cutaneous symptom improvement. In the case of cutaneous Crohn’s disease, upadacitinib resulted in reduced cutaneous symptoms without new flares. Tofacitinib resulted in completed resolution of cutaneous symptoms in our patient’s case of cutaneous lupus erythematosus. JAK inhibitors upadacitinib and tofacitinib may be potential drug candidates in patients with treatment-resistant disease, especially in cases of inflammatory cutaneous conditions such as dermatomyositis, hidradenitis suppurativa, cutaneous lupus, and cutaneous Crohn’s disease. Further studies with larger sample sizes among these conditions are warranted to assess potential broader applicability of the positive results demonstrated in our patient cases. J Drugs Dermatol. 2023;22(12):1183-1190. doi:10.36849/JDD.7500.
Treatment of hidradenitis suppurativa with tumour necrosis factor-alpha inhibitors. [2018]Hidradenitis suppurativa (HS) is a common inflammatory skin disease. Medical treatment is often disappointing and in severe disease surgery remains the therapy of choice. Extensive surgery may be effective but also mutilating. Patients experience a significant reduction in quality of life and the need for new treatment modalities are urgent. In recent years patients with HS have been treated off-label with tumour necrosis factor-alpha (TNF-alpha) inhibitors with a varying degrees of effect. We performed a systematic review of papers retrieved from two databases (PubMed and Web of Science) using the follow-ing keywords: hidradenitis suppurativa, acne inversa, infliximab, etanercept, and adalimumab. A total of 34 publications were retrieved, describing treatment of 105 patients. Most cases report treatment with infliximab (52/105). A positive treatment outcome was reported in 90/105 cases, with only 7/105 non-responders and 8/105 patients experiencing side-effects. The side-effects were comparable to those seen in other TNF-alpha inhibitor studies. In the majority of cases the treatment was effective when given as a suppressive therapy, but 15/105 cases were described with long-term remission (>or= 3 months) after the end of therapy. In most publications follow-up was, however, insufficient to allow a systematic exploration of this. TNF-alpha inhibitors seem to be effective in the treatment of HS. However, several questions remain to be answered through specific studies. This review has also identified a need for more standardized reporting of the outcomes as well as randomized controlled trials in this disease.
Pharmacokinetics of Upadacitinib in Healthy Subjects and Subjects With Rheumatoid Arthritis, Crohn's Disease, Ulcerative Colitis, or Atopic Dermatitis: Population Analyses of Phase 1 and 2 Clinical Trials. [2021]Upadacitinib (ABT-494) is a selective Janus kinase (JAK)1 inhibitor being developed for treatment of several inflammatory disorders. A population pharmacokinetic model was developed for upadacitinib using 11,658 plasma concentrations from 1145 subjects from 4 phase 1 and 5 phase 2 studies in healthy subjects and subjects with rheumatoid arthritis, Crohn's disease, ulcerative colitis, or atopic dermatitis. A 2-compartment model with first-order absorption and lag time for the immediate-release formulation and mixed zero- and first-order absorption with lag time for the extended-release formulation, and linear elimination adequately described upadacitinib plasma concentration-time profiles. The oral bioavailability of upadacitinib extended-release formulation was estimated to be approximately 80% relative to the immediate-release formulation. Covariates included in the final model were creatinine clearance, subject population (healthy subjects vs subjects with atopic dermatitis, ulcerative colitis, or Crohn's disease vs subjects with rheumatoid arthritis) and sex on apparent oral clearance and sex and body weight on apparent volume of distribution of the central compartment. Female subjects had 21% higher upadacitinib steady-state area under the plasma concentration-time curve (AUC) compared to male subjects. Compared to healthy subjects, subjects with atopic dermatitis, ulcerative colitis, or Crohn's disease had 21% higher upadacitinib steady-state AUC, while subjects with rheumatoid arthritis had 35% higher steady-state AUC. Subjects with mild or moderate renal impairment were estimated to have 10% or 22% higher AUC, respectively, compared to subjects with normal renal function. Based on final model parameter estimates, effects of the tested covariates are not expected to result in clinically relevant changes in upadacitinib steady-state exposures.
Hidradenitis suppurativa in Crohn's disease during adalimumab therapy: a paradox? [2019]A sporadic association between hidradenitis suppurativa and other diseases is reported in the literature, but few authors have described the association with Crohn's disease. Adalimumab is a fully human monoclonal antibody targeted at tumor necrosis factor alpha approved for the treatment of Crohn's disease and, recently, for active moderate to severe hidradenitis suppurativa in adult patients that do not respond adequately to systemic conventional treatment. We report an unusual case of a paradoxical effect of adalimumab in the onset of hidradenitis suppurativa in a 40-year-old woman during the treatment of Crohn's disease.
Impact of Single Nucleotide Polymorphisms of the Promoter of the TNF Gene on Adalimumab Treatment Responses in Hidradenitis Suppurativa. [2023]Results of randomized clinical trials show great variation in response to treatment with adalimumab (ADA) in hidradenitis suppurativa (HS). This varied response may be associated with genetic polymorphisms.