A Phase 2, Multi-Center Study Consisting Of A Randomized, Placebo-Controlled Period, Followed By An Open-Label Extension Period To Assess The Efficacy, Safety, And Tolerability Of Tibulizumab In Adults With Hidradenitis Suppurativa
Research on Investigational Treatment for Hidradenitis Suppurativa
David Rosmarin
Primary Investigator
Brief description of study
This is a Phase 2, multicenter study consisting of a double-blind, randomized, 3-arm, placebo-controlled period (Period 1), followed by an OLE period (Period 2) to assess the efficacy, safety, and tolerability of tibulizumab in adults with HS.
Detailed description of study
Participants will be randomized at baseline (Day 1) in a 1:1:1 ratio to receive one of the following treatments during the double-blind, placebo-controlled period (Period 1):
- Tibulizumab (150 mg) once every 4 weeks (Q4W), with an additional dose at Week 2
- Tibulizumab (300 mg) Q4W, with an additional dose at Week 2
- Placebo Q4W, with an additional dose at Week 2
During Period 1, all participants will receive tibulizumab or placebo administered via subcutaneous (SC) injection for a treatment period of 16 weeks. The last study treatment administration in Period 1 will be at Week 12 and the primary efficacy endpoint will be evaluated at Week 16. All participants who complete study treatment in Period 1, attend their Week 16 visit, and are deemed by the Investigator to have a favourable benefit:risk for continuation in the study, will be eligible to continue into
the OLE period (Period 2), during which all participants will receive tibulizumab (150 mg) administered via SC injection Q4W for a treatment period of 16 weeks. The first and last study treatment administrations in Period 2 will occur at the Week 16 and Week 28 visits, respectively, and the last efficacy visit in Period 2 will occur at Week 32.
The maximum study duration per participant is approximately 44 weeks, from screening to the end of study (EOS) safety follow-up visit. This includes a screening period of up to 30 days, a 16-week double-blind, placebo‑controlled period (Period 1), a 16-week open-label extension (OLE) period (Period 2), and an 8‑week safety follow-up period (corresponding to 12 weeks after the last study treatment administration).
Eligibility of study
You may be eligible for this study if you meet the following criteria:
- Conditions: Hidradenitis Suppurativa
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Age: 18 years - 70 years
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Gender: All
Inclusion criteria:
In order to be eligible to participate in this study, all study participants must meet all of the following criteria:
1. Male or female participant aged 18 to 70 years, inclusive, at the time of consent.
2. Participant has ≥6-month history of HS based on the investigator’s judgement (through participant
interview and/or review of medical charts) at screening.
3. Participant has HS lesions in ≥2 distinct anatomical areas, at least one of which is Hurley Stage II or III
at screening and Day 1.
4. Participant has a total AN count of ≥5 at screening and Day 1.
5. Participant had an inadequate response to an appropriate course of oral antibiotics for the treatment of
HS OR demonstrated intolerance to, OR has a contraindication to, OR exhibited recurrence after
discontinuation with oral antibiotics for the treatment of their HS, based on investigator’s judgement
through participant interview and/or review of medical history.
6. For female participant of childbearing potential involved in any sexual intercourse that could lead to
pregnancy: the participant must agree to use a highly effective contraceptive method from ≥4 weeks prior
to Day 1 until ≥12 weeks after the last study treatment administration and have a negative serum
pregnancy test at screening and a negative urine pregnancy test at Day 1.
7. For male participant involved in any sexual intercourse that could lead to pregnancy: the participant must
agree to use a highly effective contraceptive method from Day 1 until ≥12 weeks after the last study
product administration.
8. Female participant: must agree to not donate oocytes or undergo in vitro fertilization from the first study
treatment administration until ≥12 weeks after the last study treatment administration.
9. Male participant: must agree not donate sperm from the first study treatment administration until
≥12 weeks following the last study treatment administration.
10. Participant has provided written informed consent prior to any trial-related activities.
11. Participant must be willing and able to comply with all study procedures and visits, and must be available
for the duration of the study.
Exclusion criteria:
Any study participant who meets any of the following criteria will be excluded from participation in this
study:
1. Female who is breastfeeding, pregnant, or who is planning to become pregnant during the duration of the
study.
2. Participant has a draining tunnel count >20 at screening or Day 1.
3. In the opinion of the investigator performing the initial examination, the participant should not participate
in the trial (eg, due to probable noncompliance or inability to understand the nature, meaning, and
consequences of the trial, and give adequately informed consent).
4. Participant has presence of another inflammatory condition or a skin condition that may interfere with
study assessments in the opinion of the investigator.
Note: Participants who have a diagnosis of Crohn’s disease or ulcerative colitis may participate in the
study if they have no active symptomatic disease, in the opinion of the investigator.
5. Participant is known to have immune deficiency or is immunocompromised.
6. Participant has evidence or suspicion of active or latent tuberculosis.
7. Participant has a history of opportunistic, chronic, or recurrent infection requiring chronic antibiotic use,
had a serious or life-threatening infection within 2 months prior to Day 1, or had an infection requiring
systemic antibiotics within 2 weeks prior to Day 1.
8. Participant has active systemic candidiasis at screening or Day 1.
Note: Participants with urogenital candidiasis may participate in the study.
9. Participant has a positive result for hepatitis B virus (HBV; positive for hepatitis B surface antigens
[HBsAg] or positive for hepatitis B antibodies to core antigens [anti-HBc] or positive for hepatitis B
DNA; participants having a negative HBsAg and a positive anti-HBc may enroll if they have a positive
result for antibody to hepatitis B surface antigen [anti‑HBs] demonstrating natural immunity), hepatitis
C virus (HCV; positive for HCV antibodies; however, a participant with documented proof of cure from
HCV may be enrolled), or human immunodeficiency virus (HIV).
Note: Participants with a history of hepatitis B infection (HBsAg negative, anti-HBc positive, anti-HBs
negative) will be eligible if hepatitis B DNA is undetectable in serum and remains negative when checked
at 2‑month intervals.
10. Participant with any of the following laboratory values at the screening visit:
a. Hemoglobin (Hgb) is b. Absolute neutrophil count (ANC) is c. Platelet count is d. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) values ≥2 times the upper limit
of normal (ULN)
e. Estimated glomerular filtration rate Disease Epidemiology Collaboration (CKD-EPI) equation
11. Participant has a history of anaphylaxis to any biologic therapy or vaccine.
12. Participant has a history of cancer or lymphoproliferative disease within 5 years prior to Day 1.
Note: Participants with successfully treated nonmetastatic cutaneous squamous cell or basal cell
carcinoma and/or localized carcinoma in situ of the cervix are not to be excluded.
13. Participant has a lifetime history of suicide attempt (including an actual attempt, interrupted attempt, or
aborted attempt), had suicidal ideation in the past 6 months as indicated by a positive response (“Yes”)
to either Question 4 or Question 5 of the “Baseline/Screening” version of the C-SSRS at Screening, had
suicidal ideation since last visit as indicated by a positive response (“Yes”) to either Question 4 or
Question 5 of the “Since Last Visit” version of the C-SSRS at Day 1, or who, in the investigator's opinion,
poses a significant suicide risk.
14. Participant has a known history of clinically significant drug or alcohol abuse in the last 6 months prior
to screening.
15. Participant had a major surgery within 4 weeks prior to Day 1 or has a major surgery planned during the
study.
16. Participant has any clinically significant medical condition or physical/laboratory/ECG/vital signs
abnormality that would, in the opinion of the investigator, put the participant at undue risk, interfere with
interpretation of study results, or impede the participants ability to complete the entire duration of the
study.
17. Participant has used any of the following within the specified periods:
a. Any prior use of anti-interleukin (IL)-17 or anti-B-cell activating factor (BAFF) therapies.
b. B cell-depleting biologics within 12 months prior to Day 1.
c. Glucagon-like peptide-1 (GLP-1) receptor agonists, or any other therapy that causes significant
weight loss, within 6 months prior to Day 1.
Note: The use GLP-1 agonists or any other therapies that cause significant weight loss will be allowed
if the participant has been on a stable dose for ≥6 months prior to Day 1 and continues to use the
same agent at the same dose throughout the study.
d. Marketed (eg, adalimumab) or investigational biological agent within 12 weeks or 5 half-lives
(whichever is longer) prior to Day 1.
e. Receipt of immunoglobulins (Ig) or blood products within 4 weeks prior to Day 1.
f. Receipt of a live or live-attenuated vaccine within 4 weeks prior to Day 1 or plans to receive a live
or live-attenuated vaccine during the study.
g. Systemic non-biologic therapies that could affect HS within 4 weeks prior to Day 1, including, but
not limited to, methotrexate, cyclosporine, retinoids, Janus kinase (JAK) inhibitors, Bruton’s tyrosine
kinase (BTK) inhibitors, fumaric acid esters, and oral or injectable corticosteroids.
Note: Intranasal corticosteroids and inhaled corticosteroids are allowed. Eye and ear drops containing
corticosteroids are also allowed.
h. Systemic antibiotics for the treatment of HS within 4 weeks prior to Day 1.
Note: The use of tetracyclines is allowed if the participant has been on a stable dose for ≥4 weeks
prior to Day 1, and participant agrees to maintain current dose and frequency throughout the study.
i. Surgical, laser or intense pulse light intervention in anatomic areas of HS lesions within 4 weeks
prior to Day 1.
1. Nonbiological investigational product or medical device within 4 weeks prior to Day 1.
j. Analgesics for pain (HS or non-HS related) or opioid analgesics (except tramadol) within 2 weeks of
Day 1.
Note: The use of oral, non-opioid analgesics for the management of non-HS medical conditions
(eg, osteoarthritis) will be allowed if the participant has been on a stable dose for ≥2 weeks prior to
Day 1, and participant agrees to maintain current dose and frequency throughout the study.
k. Prescription topical medication for the treatment of HS within 2 weeks prior to Day 1.
Note: Stable use of antiseptics will be allowed.
18. Participant has a known or suspected allergy to ZB-106 (tibulizumab) or any component of the
investigational product.
19. Participant is unable to tolerate SC drug administration.
20. Participant is institutionalized because of legal or regulatory order
This study investigates an investigational medication for hidradenitis suppurativa (HS), a skin condition that causes small, painful lumps under the skin. The purpose of this study is to assess the effectiveness and safety of the investigational medication in adults with HS. Participants will be divided into three study arms: two arms will receive different doses of the investigational medication, and one will receive a placebo, which is an inactive substance that looks like the investigational medication but does not contain any medicine.
In the first part of the study, participants will receive either the investigational medication or a placebo through a subcutaneous injection for 16 weeks. After this period, participants may continue into an open-label extension where everyone will receive the investigational medication for another 16 weeks. The study will involve regular visits to monitor the participants' health and response to the treatment.
- Who can participate: Adults aged 18 to 70 years with a history of hidradenitis suppurativa for at least 6 months can participate. Participants must have HS lesions in at least two distinct areas, with at least one area being Hurley Stage II or III. They should have tried antibiotics for HS without success or have a contraindication to them.
- Study details: Participants will receive injections under the skin of either the investigational medication or a placebo every four weeks, with some additional doses. After the initial 16-week period, all participants continuing will receive the investigational medication for another 16 weeks.
- Study timelines: The study will last approximately 44 weeks.
