E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Active moderate to severe hidradenitis suppurativa |
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E.1.1.1 | Medical condition in easily understood language |
Pain due to a skin condition that causes small, painful lumps to form under the skin and scarring on the skin. |
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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 | 100000004858 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of sonelokimab at 2 different dose levels (120 mg, 240 mg) compared with placebo in the treatment of participants with active moderate to severe hidradenitis suppurativa. |
|
E.2.2 | Secondary objectives of the trial |
1. To evaluate the safety and tolerability of sonelokimab at 2 different dose levels (120 mg, 240 mg) compared with placebo in the treatment of participants with active moderate to severe hidradenitis suppurativa;
2. To assess the pharmacokinetics (PK) and immunogenicity of sonelokimab at 2 different dose levels (120 mg, 240 mg) in the treatment of participants with active moderate to severe hidradenitis suppurativa. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. ≥18 years of age.
2. Diagnosed with HS and has a history of signs and symptoms of HS dating back at least 6 months.
3. Total AN count (i.e., abscesses and/or inflammatory nodules) of ≥5.
4. Subject has HS lesions present in ≥2 distinct anatomical areas at least one of which must contain single or multiple fistulas (i.e., be Hurley Stage II or III);
5. Subject had an inadequate response to appropriate systemic antibiotics for treatment of HS (or demonstrated intolerance to, or had a contraindication to, systemic antibiotics for treatment of their HS).
6. Participants must a suitable candidate for treatment with adalimumab per approved local product information. If a chest X-ray or computed tomography (CT) for tuberculosis (TB) screening is required per local guidance, the X-ray or CT must have been taken within 3 months prior to the Screening.
7. If the subject is female, must be of non-childbearing potential or if of childbearing potential, participant must agree to use highly effective methods of contraception.
8. Women of childbearing potential must have a negative serum human chorionic gonadotropin (hCG) pregnancy test at screening and a negative urine pregnancy test at Week 0/Day1 prior to the first administration of study treatment.
9. If male, participant must be willing to use a condom when sexually active with a partner of childbearing potential during the study and for 12 weeks after the last dose of study drug, unless surgically sterile.
10. Participant is considered reliable and capable of adhering to the protocol, visit schedule, or medication intake according to the judgment of the investigator.
11. Participant is able to understand and provide signed informed consent. |
|
E.4 | Principal exclusion criteria |
1. Known hypersensitivity to sonelokimab, adalimumab or any of its excipients.
2. Draining fistula count of ≥20.
3. Any other active skin disease or condition that may interfere with the assessment of HS.
4. Subject who currently use or plan used one or more prohibited treatments specified in this protocol.
5. Subjects enrolling in the non-antibiotic strata: use of systemic antibiotics for the treatment of HS within 28 days.
6. Previous exposure or subject in a study of brodalumab (anti-IL-17RA) and/or bimekizumab (anti-IL17 A/F).
7. Unsuitable for interleukin (IL)-17A therapy and anti-tumor necrosis factor alpha (TNFα) therapy.
8. Prior exposure to more than 2 biologic response modifiers.
9. Diagnosis of ulcerative colitis or Crohn’s disease.
10. Subject has an active infection or history of infections.
11. Participant with:
a. History of active TB.
b. Evidence of TB infection, unless the following criteria apply:
i. A full TB work-up within 12 weeks establishes no evidence of active or latent TB infection.
ii. Positive for latent TB per work-up must have completed sufficient treatment at least 4 weeks prior.
12. Any current nontuberculous mycobacterial (NTM) infection or any history of pulmonary NTM infection.
13. Concurrent acute or chronic viral hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
14. Evidence of human immunodeficiency virus (HIV) infection.
15. Tests positive for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection.
16. Concurrent malignancy or a history of malignancy during the past 5 years of with the following exceptions:
a. ≤3 successfully excised or ablated, basal cell carcinomas of the skin.
b. One squamous cell carcinoma of the skin not worse than Stage T1 that has been successfully treated, with no signs of recurrence or metastases for at least the past 2 years.
c. Actinic keratosis.
d. Squamous cell carcinoma in situ of the skin successfully treated >6 months.
e. Localized carcinoma in situ of the cervix treated and considered cured.
17. History of a lymphoproliferative disorder including lymphoma or current signs and symptoms suggestive of lymphoproliferative disease.
18. Primary immunodeficiencies, prior splenectomy, or suppressive conditions, including subjects taking immunosuppressive therapy following organ transplants.
19. Had major surgery (e.g., hip replacement, aneurysm removal) within 6 months or is planning to have major surgery during the study.
20. History or concurrent clinically significant medical conditions or any other reason, including any physical, psychological, or psychiatric condition, that would compromise the safety or interfere with the subject’s participation in the study, would make the participant an unsuitable candidate to receive study drug, or would put the participant at risk.
21. Has received live (including attenuated) vaccination within 8 weeks or planned during the study and up to at least 12 weeks after the last dose of study drug.
22. Has received Bacillus Calmette-Guérin vaccination within 1 year.
23. Presence of active suicidal ideation, or positive suicidal behavior; any history of suicidal attempt (including an actual attempt, interrupted attempt, or aborted attempt), or suicidal ideation in the past 6 months.
24. Presence of moderately severe depression or severe depression. Subjects are permitted to use 1 medication to treat depression provided dose is stable for 4 weeks prior. Subjects on multiple medications for depression are excluded from the study.
25. Severe cardiovascular comorbidities including history of myocardial infarction, unstable angina pectoris, stroke or heart failure New York Heart Association (NYHA) III or IV), or uncontrolled hypertension.
26. Clinically significant ECG abnormalities on centrally read ECG at the Screening.
27. Subject with laboratory abnormalities at the Screening.
28. Subject is enrolled in another interventional investigational study for a device or drug or has been so enrolled in the last 28 days prior or within 5 half-lives of the study drug prior to the Screening, whichever is longer.
29. Subject is pregnant or breastfeeding or plans to become pregnant while enrolled in the study
and up to 12 weeks after the last dose of study drug;
30. History of chronic alcohol or drug abuse in the past year.
31. Subject is an employee, or direct relative of an employee, of the sponsor, at a study site, or of a third-party organization involved in the study. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
1. Percentage of participants achieving Hidradenitis Suppurativa Clinical Response (HiSCR75) 75 at Week 12, where HiSCR75 is defined as at least a 75% reduction from baseline in abscess and inflammatory nodule (AN) count, with no increase from baseline in abscess or draining fistula count. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
From baseline to week 12. |
|
E.5.2 | Secondary end point(s) |
1. Proportion of participants achieving HiSCR50 at Week 12.
2. Change from baseline in International Hidradenitis Suppurativa Severity Score System (IHS4) at week 12;
3. Proportion of participants achieving a Dermatology Life Quality Index (DLQI) total score of ≤5 at Week 12.
4. Proportion of participants achieving at least 30% reduction and at least 1-unit reduction from baseline in Numerical Rating Scale (NRS) 30 in Patient's Global Assessment (PGA) of Skin Pain at Week 12 among subjects with baseline NRS ≥3. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
From baseline to week 12. |
|
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 | Yes |
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 | No |
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 | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 35 |
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 |
Poland |
Bulgaria |
Netherlands |
Germany |
Ireland |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |