Clinical trial NCT06326476: An Open-label, Time-lagged, Dose-escalation Study to Evalaute the Safety and Efficacy of Subcutaneous Siplizumab in the Treatment of Hidradenitis Suppurativa.
Official title: An Open-label Parallel Group Pilot Study to Demonstrate the Safety and Efficacy of Subcutaneous Siplizumab in the Treatment of Hidradenitis Suppurativa
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Hidradenitis Suppurativa
Lead sponsor: University of Alabama at Birmingham
Sponsor class: OTHER
Collaborators: name: ITB-Med LLC
First posted: 2024-03-22
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is to investigate the efficacy of siplizumab in the treatment of Hidradenitis Suppurativa.

Detailed description: Subjects will be assigned to receive seven subcutaneous doses of siplizumab over an 8 week period. The study will include up to 3 investigational treatment cohorts, 10 mg, 20 mg and a 40 mg cohort. Each cohort will contain from 3-6 subjects. The cohort will be administered either 10 mg, 20mg, or 40mg siplizumab SC weekly from baseline (week 0) to week 4 and a dose at weeks 6 and 8. Assessments will be performed weekly from baseline (week 0) through week 6 and biweekly through week 12 (weeks 8, 10 \& 12) by an investigator. Weeks 5 and 10 will be telephone visits and will not include physician HS assessments. All other visits will be conducted in person. During all visits, subjects will also be asked to complete a quality of life questionnaire (DLQI) and Visual Analog Scale (VAS) for pain assessment.

A total enrollment of 12 subjects is anticipated in this pilot study; however, up to 18 patients may be enrolled.

Eligibility criteria: Inclusion Criteria:

* Male or Female at least 18 years of age, and provide informed consent prior to study procedures.
* Have moderate to severe HS classified as Hurley stage II or III for at least 6 months refractory to conventional therapies with a total AN count of greater than or equal to 5 prior to enrollment/randomization
* Failed at least 1 course of oral antibiotics for treatment of HS (or demonstrated intolerance to, or had a contraindication to oral antibiotics for treatment of their HS).
* Women of Childbearing potential must have a urine pregnancy test at screening, wk 0 and prior to administration of the study medication
* Women of childbearing potential must be willing to continue a highly effective method of birth control throughout the study (oral, injected or implanted hormonal methods of contraception; placement of an intrauterine device or intrauterine system; barrier methods: condom or occlusive cap (diaphragm or cervical/vault caps) plus spermicidal foam/gel/film/cream/suppository (if available in their locale); male partner sterilization (the vasectomized partner should be the sole partner for that participant); true abstinence (when this is in line with the preferred and usual lifestyle of the participant).
* Negative screening for tuberculosis (TB) (Quantiferon Gold, T-spot) within 3 months prior to screening
* If a positive history of latent tuberculosis:

  * Currently receiving treatment for latent TB per standard of care
  * Have documentation of having completed treatment within 5 years prior to baseline
* Agree not to have a live vaccination during the study.

Exclusion Criteria:

* Any other active skin disease that in the opinion of the investigator would interfere with the assessment of HS
* Have greater than 20 draining fistulas at screening or Day 1 prior to enrollment/randomization
* Receipt of non-biologic treatments for HS within 4 weeks prior to baseline other than antibiotics or hormonal therapy
* Receipt of biologic agents within 3 months prior to baseline
* Receipt of any other investigational product within 3 months prior to baseline
* Receipt of new oral antibiotics or hormonal therapy within 6 weeks prior to baseline.

  * Subjects may be included if they are on steady dose of doxycycline or tetracycline antibiotics only for at least 6 weeks prior to baseline visit and may not change or discontinue dose during course of study.
* Receipt of intralesional kenalog injections within 2 weeks prior to baseline
* Any uncontrolled diagnosis or condition that in the opinion of the investigator will interfere with the assessments or the study.
* Currently has a malignancy or a history of a malignancy within 5 years before screen (except successfully treated non-melanoma skin cancer or cervical carcinoma in situ)
* History of an ongoing, chronic or recurrent infectious disease
* Are currently pregnant, breastfeeding, or planning to get pregnant during the study.
* Previous hypersensitivity reaction to siplizumab or to any of the components
* Known infection with HIV, hepatitis B or hepatitis C at screening or randomization.

Patients who are Hepatitis B Core antibody and/or Hep B Surface Antigen positive will be excluded from this study. Patients who are Hepatitis C ab positive will also be excluded from this study.

* Underlying condition (including, but not limited to metabolic, hematologic, renal, hepatic, pulmonary, neurologic, endocrine, cardiac, infectious or gastrointestinal) which in the opinion of the investigator significantly immunocompromises the subject and/or places the subject at unacceptable risk for receiving an immunomodulatory therapy.
* Any of the following laboratory abnormalities within 30 days of enrollment:

  * White blood count (WBC) \< 3 x 103/μL;,
  * CD4+ count below the lower limit of normal,
  * Platelet count \< 150,000 /μL,
  * Hemoglobin \< 10 g/dL,
  * ALT ≥ 2x upper limit of normal (ULN) or
  * AST ≥ 2x ULN
  * Serum creatinine \>1.5x ULN in adults.
  * Positive molecular testing of SARS-CoV-2
  * ALC less than 800 lymphocytes/mm3

Primary outcomes:
measure: Change in inflammatory lesion counts
timeFrame: Weeks 4, 8 and 12
Secondary outcomes:
measure: Change in Hidradenitis Suppurativa Clinical Response (HiSCR)
timeFrame: Weeks 4,8, and 12.
measure: Change in Hurley Stage
timeFrame: Weeks 4,8, and 12
measure: Change in Dermatology Life Quality Index (DLQI) scores
timeFrame: Weeks 4, 8, and 12
measure: Improvement in Visual Analogue Scale (VAS) pain scores
timeFrame: Weeks 4, 8, and 12
measure: Change in Lesion Counts
timeFrame: Weeks 4, 8, and 12
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
Study officials:
affiliation: University of Alabama at Birmingham
name: Tiffany Mayo, MD
role: PRINCIPAL_INVESTIGATOR
References: