| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | |
| E.1.1.1 | Medical condition in easily understood language | |
| E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 | | E.1.2 | Level | LLT | | E.1.2 | Classification code | 10020041 | | E.1.2 | Term | Hidradenitis suppurativa | | E.1.2 | System Organ Class | 10040785 - Skin and subcutaneous tissue disorders | |
| E.1.3 | Condition being studied is a rare disease | Yes |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial | Part A
- To explore the efficacy of izokibep as measured by HiSCR75 at Week 12
Part B
- To demonstrate that one or both treatment regimens of izokibep is efficacious compared to placebo, as measured by HiSCR75 at Week 16 | |
| E.2.2 | Secondary objectives of the trial | Part A
-Explore the safety & tolerability
-Explore the immunogenicity of izokibep as measured by the presence of ADAs
Part B
-Demonstrate that one or both regimens of izokibep is efficacious, as measured by:
•Percentage of subjects achieving HiSCR90 at Week 16
•Percentage of subjects achieving HiSCR100 at Week 16
•Percentage of subjects achieving HiSCR50 at Week 16
•Percentage of subjects that experience ≥ 1 disease flare through 16 weeks of treatment
•Percentage of subjects with baseline Hurley Stage II who achieve AN count of 0, 1, or 2 at Week 16
• Percentage of subjects achieving at least 3 point reduction from baseline in NRS in Patient Global Assessment of Skin Pain at its worst at Week 16 among participants with baseline NRS ≥4
-Assess the safety and tolerability of izokibep as measured by the incidence of TEAEs, events of interest, SAEs, and clin. significant laboratory values and vital signs
-Assess the immunogenicity of izokibep as measured by the presence of ADAs | |
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria | - Subject (male and female) must be ≥ 18 and ≤ 75 years
- Diagnosis of HS for ≥ 1 year
- HS lesions present in ≥ 2 distinct anatomic areas, one of Hurley Stage II
or Hurley Stage III
- A total AN count of ≥ 5 at screening
- Subject must have had an inadequate response to oral antibiotics (defined as ≥ 3-month treatment with an oral antibiotic for treatment of HS) OR exhibited recurrence after discontinuation to, OR demonstrated intolerance to, OR have a contraindication to oral antibiotics for treatment of their HS
- Subject must agree to use daily (throughout the duration of the study) one of the following over-the-counter topical antiseptics on their body areas affected with HS suppurativa lesions: chlorhexidine gluconate, triclosan, benzoyl peroxide, or diluted bleach in bathwater.
- Subject must be willing to complete a daily skin pain diary 7 consecutive days prior to Day 1
- No known history of active tuberculosis
- Subject has a negative tuberculosis test at screening
- Male and Female participants of childbearing potential must use effective methods of contraception
For a complete overview of the inclusion criteria refer to the protocol. | |
| E.4 | Principal exclusion criteria | - Draining fistula count of > 20 at screening or Day 1 prior to enrollment/randomization
- Outpatient surgery ≤ 8 weeks prior or inpatient surgery ≤ 12 weeks prior to enrollment/randomization
- Other active skin disease or condition (eg, bacterial, fungal or viral infection) that could interfere with study assessments
- Active inflammatory bowel disease (IBD) within 3 years prior to enrollment
- Chronic pain not associated with HS (eg, fibromyalgia).
- Uncontrolled, clinically significant system disease such as diabetes mellitus, cardiovascular disease including moderate to severe heart failure (New York Heart Association class III/IV), moderate to severe renal disease, moderate to severe liver disease or hypertension
- History of demyelinating disease (including myelitis) or neurological symptoms suggestive of demyelinating disease
- Malignancy within 5 years except treated and considered cured cutaneous squamous or basal cell carcinoma, in situ cervical cancer, or in situ breast ductal carcinoma
- The subject is at risk of self-harm or harm to others as evidenced by past suicidal behavior or endorsing items 4 or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS) assessed at screening. Subjects with major depressive disorder are permitted in the study if they are considered by the investigator to be stable and are taking no more than 1 medication. Subjects must have been on a stable dose within the 3 months prior to the first dose of study drug
- History or evidence of any clinically significant disorder (including psychiatric), condition, or disease that, in the opinion of the Investigator, may pose a risk to subject safety or interfere with the study evaluation, procedures, or completion
- Any active infection for which oral anti-infectives (antibiotics, antivirals, antifungals) were used ≤ 14 days prior to first dose of study drug (except for the use of a stable dose allowable antibiotics [doxycycline or minocycline only] for HS)
- A serious infection requiring hospitalization or IV anti-infectives (antibiotics, antivirals, antifungals) ≤ 30 days prior to first dose of study drug
- Recurrent or chronic infections or other active infections that in the opinion of the investigator might cause this study to be detrimental to the subject
- Candida infection requiring systemic treatment ≤ 3 months prior to first dose of study drug
- Tuberculosis or fungal infection seen on available chest x-ray taken ≤ 3 months of screening or at screening
- Known history of human immunodeficiency virus (HIV)
- Previous exposure to izokibep or any other IL-17 receptor inhibitors (eg, secukinumab, ixekizumab, bimekizumab, brodalumab)
- Prior exposure to biologics that have a potential for or known association with progressive multifocal leukoencephalopathy (ie, natalizumab [Tysabri ®], rituximab [Rituxan®], or efalizumab [Raptiva®])
- Exposure to TNF-α inhibitors, IL-1, IL-12, IL-23, or IL-12/23 receptor inhibitors within 5 half-lives prior to first dose of study drug
- Exposure to the following ≤ 12 weeks prior to first dose of study drug
• Other experimental or commercially available biologic or biosimilar therapies (within 12 weeks or 5 half-lives, whichever is longer)
• IV gamma-globulin or Prosorba column therapy
• Exposure to the following ≤ 4 weeks prior to first dose of study drug
• JAK inhibitors (eg, tofacitinib, upadacitinib)
• Oral or injectable corticosteroids (including intralesional injections)
• Cyclosporine, azathioprine, tacrolimus
• Other systemic treatments for autoimmune/inflammatory conditions not listed above or below (eg, mycophenolate mofetil, retinoids, fumarates, apremilast, or phototherapy [eg, PUVA, UVA, UVB]), except for allowable stable dose antibiotics (doxycycline or minocycline)
• Laser or intense pulse light therapy in anatomic areas of HS lesions
- For subjects entering study with a permitted oral antibiotic treatment (doxycycline or minocycline only) for HS: not on a stable dose for ≥ 4 weeks prior to first dose of study drug
- For subjects entering study with oral, non-opioid analgesics: not on a stable dose for ≥5 days prior to first dose of study drug
- Required or is expected to require, opioid analgesics for any reason (excluding tramadol) during the study
- Received live vaccination ≤ 12 weeks prior to dosing or scheduled to receive a live vaccine ≤ 12 weeks following the last dose of study drug
- Positive hepatitis B surface antigen (HBsAg) or detected sensitivity on the hepatitis B virus DNA polymerase chain reaction (PCR) qualitative test for hepatitis B core antibodies (HBcAB)/Hepatitis B surface antibodies (HBsAb) positive subjects OR positive Hepatitis C virus antibody test at screening
- Laboratory abnormalities at screening as described
For a complete overview of the exclusion criteria refer to the protocol. | |
| E.5 End points |
| E.5.1 | Primary end point(s) | Part A
HiSCR75 = hidradenitis suppurativa clinical response at week 12
Part B
HiSCR75 at week 16 | |
| E.5.1.1 | Timepoint(s) of evaluation of this end point | Part A
HiSCR75 - at Week 12
Part B
HiSCR75 - at Week 16 | |
| E.5.2 | Secondary end point(s) | Part A
- TEAEs and SAEs
- Laboratory values and vital signs at collected timepoints
- ADAs (= anti-drug antibodies)
Part B
- HiSCR90 at Week 16
- HiSCR100 at Week 16
- HiSCR50 at Week 16
- HS flares through Week 16
- AN count of 0, 1, or 2 at Week 16
- NRS30 in Patient Global Assessment of Skin Pain at its worst at Week 16
- TEAEs, events of interest, and SAEs
- Laboratory values and vital signs at collected timepoints
-ADAs | |
| E.5.2.1 | Timepoint(s) of evaluation of this end point | Part A and Part B
- TEAEs and SAEs events of interest
- Laboratory values and vital signs at collected timepoints
- ADAs (= anti-drug antibodies)
From start of treatment to end of study.
- HiSCR90 at Week 16
- HiSCR100 at Week 16
- HiSCR50 at Week 16
- HS flares through Week 16
- AN count of 0, 1, or 2 at Week 16
- NRS30 in Patient Global Assessment of Skin Pain at its worst at Week 16 | |
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description | |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description | | Part A proof-of-concept, single-arm, open-label part | |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 4 |
| E.8.3 | The trial involves single site in the Member State concerned | No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 25 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned | | Canada | | United States | | Germany | | Hungary | | Poland | | Spain | |
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 | Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial | |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 2 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 2 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
