Lutikizumab for Hidradenitis Suppurativa

(Intrepid Trial)

Recruiting in Palo Alto (17 mi)

+116 other locations

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: AbbVie

Disqualifiers: Hepatitis, HIV, Tuberculosis, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

Hidradenitis suppurativa (HS) is a chronic and often painful inflammatory skin disease which includes the forming of lumps, abscesses and scars in areas of the skin such as under the breasts, under armpits, inner thighs, groin and buttocks. This study will compare lutikizumab versus placebo for the treatment of adult and adolescent participants with moderate to severe HS . Lutikizumab is an investigational drug being developed for the treatment of HS. During Period 1 of the study, participants will placed in 1 of 2 groups called treatment arms. There is a 1 in 2 chance that participants will be assigned to placebo. Around 1280 adult and adolescent participants with moderate to severe HS will be enrolled in the study at approximately 275 sites world wide. During Period 2, participants that were part of the lutikizumab treatment arm in Period 1 will be re-randomized to 1 of 2 lutikizumab treatment arms. Participants that were part of the Placebo arm in Period 1 will start Period 2 with an initiation of lutikizumab followed by a re-randomization to 1 of 2 lutikizumab treatment arms. In Period 1, participants will receive subcutaneous injections of lutikizumab or placebo every week for 16 weeks. In Period 2, participants that were randomized to lutikizumab in Period 1 will receive subcutaneous injections of lutikizumab every week or every other week for 36-weeks. Participants that were randomized to the placebo arm in Period 1 will receive subcutaneous injections of lutikizumab every week for 16 weeks, then either every week or every other week for 20 weeks There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires and diaries.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug Lutikizumab for treating Hidradenitis Suppurativa?

While there is no direct data on Lutikizumab for Hidradenitis Suppurativa, similar treatments targeting the IL-17 pathway, like secukinumab and brodalumab, have shown effectiveness in about two-thirds of patients with this condition. This suggests that targeting similar pathways might be beneficial. ^{1 2 3 4 5}

How does the drug Lutikizumab differ from other treatments for hidradenitis suppurativa?

Lutikizumab is unique because it targets interleukin-1 (IL-1), a different pathway compared to other treatments like adalimumab, which targets tumor necrosis factor-alpha (TNF-alpha). This novel approach may offer an alternative for patients who do not respond well to existing therapies. ^{3 6 7 8 9}

Research Team

ABBVIE INC.

Principal Investigator

AbbVie

Eligibility Criteria

This trial is for adults and adolescents with moderate to severe Hidradenitis Suppurativa (HS), a painful skin condition. Participants must have been diagnosed at least 6 months ago, have five or more abscesses or nodules, and HS lesions in two areas of the body, one being at least Hurley Stage II.

Inclusion Criteria

I have HS lesions in two or more separate areas.

I have been diagnosed with moderate to severe HS for at least 6 months.

I have 5 or more abscesses or inflamed nodules.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Period 1

Participants receive subcutaneous injections of lutikizumab or placebo every week for 16 weeks

16 weeks

Weekly visits (in-person)

Treatment Period 2

Participants receive subcutaneous injections of lutikizumab every week or every other week for up to 36 weeks

36 weeks

Weekly or bi-weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Lutikizumab (Monoclonal Antibodies)

Trial Overview The study tests Lutikizumab against a placebo in treating HS. Initially, participants are randomly assigned to receive either Lutikizumab or placebo injections weekly for 16 weeks. Afterwards, they may continue with different dosing schedules of Lutikizumab for up to 36 weeks.

Participant Groups

Group I: Period 2: Placebo to Lutikizumab Group Every Week Experimental Treatment 1 Intervention

Participants that were assigned Placebo in Period 1 and initiated lutikizumab in Period 2 will then be re-randomized to lutikizumab Dose A every week through Week 52

Group II: Period 2: Placebo to Lutikizumab Group Every Other Week Experimental Treatment 2 Interventions

The participants that were assigned Placebo in Period 1 and initiated lutikizumab in Period 2 will then be re-randomized to lutikizumab Dose A every other week through Week 52

Group III: Period 2: Placebo to Lutikizumab Group Experimental Treatment 1 Intervention

Participants randomized to Placebo in Period 1 who complete Week 16 of the study will initiate lutikizumab with Dose B followed by Dose A every week.

Group IV: Period 2: Lutikizumab Every Week Experimental Treatment 1 Intervention

Participants randomized to lutikizumab in Period 1 who complete Week 16 of the study will be re-randomized to lutikizumab Dose A through Week 52

Group V: Period 2: Lutikizumab Every Other Week Experimental Treatment 2 Interventions

Participants randomized to lutikizumab in Period 1 who complete Week 16 of the study will be re-randomized to lutikizumab Dose A every other week though week 52

Group VI: Period 1 Experimental Treatment 2 Interventions

Participants will be randomized to either Lutikizumab Dose B at baseline followed by Lutikizumab Dose A, or a matching placebo dose equivalent for both, every week through Week 16 .

Who Is Running the Clinical Trial?

AbbVie

Lead Sponsor

Trials

1,079

Recruited

535,000+

Founded

2013

Headquarters

North Chicago, USA

Known For

Immunology treatments

Top Products

Humira (adalimumab), Skyrizi (risankizumab), Rinvoq (upadacitinib)

Dr. Roopal Thakkar

AbbVie

Chief Medical Officer since 2023

MD from Wayne State University School of Medicine

Robert A. Michael

AbbVie

Chief Executive Officer

Bachelor's degree in Finance from the University of Illinois

Findings from Research

In a study of 26 individuals with hidradenitis suppurativa treated with risankizumab, 69.2% achieved a significant clinical response by week 16, indicating the efficacy of IL-23 antagonism in this condition.

Clinical response was linked to male gender, higher testosterone levels, and lower FSH levels, suggesting that these hormonal markers, along with specific immune cell profiles, could serve as potential biomarkers for predicting treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Baseline clinical, hormonal and molecular markers associated with clinical response to IL-23 antagonism in hidradenitis suppurativa: A prospective cohort study. Flora, A., Kozera, EK., Jepsen, R., et al.[2023]

In patients with severe hidradenitis suppurativa (HS), there is an increase in specific inflammatory monocytes and a unique cytokine profile, indicating a complex immune response that could guide treatment choices.

Treatment with etanercept, a TNF blocker, showed clinical improvement linked to increased production of IL-1β and IL-17 in blood cells, suggesting that monitoring these cytokines could help predict treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Compartmentalized Cytokine Responses in Hidradenitis Suppurativa. Kanni, T., Tzanetakou, V., Savva, A., et al.[2018]

In a phase 2 clinical trial, the drug fostamatinib showed a 75% clinical response rate in patients with hidradenitis suppurativa, particularly benefiting those with high levels of inflammation and IgG.

Serum proteomic analysis revealed that responders to fostamatinib had significant reductions in inflammatory markers, suggesting that targeting B-cell activity may effectively alter the disease's inflammatory profile and help identify potential biomarkers for therapy response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alterations to the Hidradenitis Suppurativa Serum Proteome with Spleen Tyrosine Kinase Antagonism: Proteomic Results from a Phase 2 Clinical Trial. Flora, A., Jepsen, R., Pham, J., et al.[2023]

Adalimumab, a TNF-α inhibitor, has variable effectiveness in treating hidradenitis suppurativa (HS), highlighting the need for new therapeutic options.

Promising new treatments under investigation include anti-IL-17 biologics like bimekizumab and secukinumab, which are in phase III trials, and IL-1α targeting with bermekimab, showing encouraging results in early studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Target molecules for future hidradenitis suppurativa treatment. Zouboulis, CC., Frew, JW., Giamarellos-Bourboulis, EJ., et al.[2022]

In a phase II study involving 243 patients with moderate-to-severe hidradenitis suppurativa (HS), risankizumab did not meet the primary endpoint of achieving HS Clinical Response (HiSCR) at week 16, indicating it may not be an effective treatment for this condition.

The safety profile of risankizumab was generally favorable, with low rates of treatment-emergent adverse events across all treatment groups, suggesting that while it may not be effective, it is also not associated with significant safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Risankizumab for the Treatment of Hidradenitis Suppurativa: A Phase 2, Randomized, Placebo-Controlled Trial. Kimball, AB., Prens, EP., Passeron, T., et al.[2023]

A patient with hidradenitis suppurativa (HS) initially responded well to infliximab, a TNF-alpha antagonist, but experienced an infusion reaction, highlighting the potential for adverse effects with certain treatments.

Switching to adalimumab, another TNF-alpha inhibitor, resulted in significant and sustained improvement in the patient's condition for over 15 months, suggesting that adalimumab is a safe and effective alternative for patients who cannot tolerate infliximab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful Treatment of Recalcitrant Hidradenitis Suppurativa with Adalimumab. Gorovoy, I., Berghoff, A., Ferris, L.[2021]

In adult patients with hidradenitis suppurativa (HS), adalimumab reaches steady serum concentrations of 10-12 µg/mL by week 2 and maintains these levels through week 12, indicating effective dosing.

The development of anti-adalimumab antibodies (AAA) was low (10% in phase II and 7% in phase III studies), but the presence of AAA was associated with decreased drug concentrations, which could potentially reduce the treatment's efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population Pharmacokinetics and Immunogenicity of Adalimumab in Adult Patients with Moderate-to-Severe Hidradenitis Suppurativa. Nader, A., Beck, D., Noertersheuser, P., et al.[2018]

References

1. United States pubmed.ncbi.nlm.nih.gov

Medical management of hidradenitis suppurativa. [2018]

2. United States pubmed.ncbi.nlm.nih.gov

Treatment Outcomes of IL-17 Inhibitors in Hidradenitis Suppurativa: A Systematic Review. [2022]

3. Denmark pubmed.ncbi.nlm.nih.gov

Baseline clinical, hormonal and molecular markers associated with clinical response to IL-23 antagonism in hidradenitis suppurativa: A prospective cohort study. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Compartmentalized Cytokine Responses in Hidradenitis Suppurativa. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Alterations to the Hidradenitis Suppurativa Serum Proteome with Spleen Tyrosine Kinase Antagonism: Proteomic Results from a Phase 2 Clinical Trial. [2023]

6. Denmark pubmed.ncbi.nlm.nih.gov

Target molecules for future hidradenitis suppurativa treatment. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Risankizumab for the Treatment of Hidradenitis Suppurativa: A Phase 2, Randomized, Placebo-Controlled Trial. [2023]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Successful Treatment of Recalcitrant Hidradenitis Suppurativa with Adalimumab. [2021]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Population Pharmacokinetics and Immunogenicity of Adalimumab in Adult Patients with Moderate-to-Severe Hidradenitis Suppurativa. [2018]