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 |
Hidradenitis suppurativa, HS disease |
|
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 |
|
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 determine the safety and tolerability of
INCB054707 |
|
E.2.2 | Secondary objectives of the trial |
To determine the systemic exposure to INCB054707. To determine the efficacy of INCB054707. To assess the need for rescue lesional treatment. To assess patient-reported quality-of-life burden. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Men and women aged 18 to 75 years at the time of consent.
2. Diagnosis of HS (confirmed by a dermatologist) with a disease duration of at least 6 months before screening.
3. Stable course of HS for at least 90 days before screening, as determined by the investigator.
4. HS lesions present in at least 2 distinct anatomic areas, 1 of which must be Hurley Stage II (ie, recurrent abscessed with tract formation and cicatrization; single or multiple, widely separated lesions) or Hurley Stage III (ie, diffuse or near diffuse involvement, or multiple interconnected tracts and abscesses across the entire area) at screening.
5. Total AN count of at least 3 at screening and baseline.
6. Willingness to avoid pregnancy or fathering children based on the criteria below:
a. Male participants must agree to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from screening through 90 days after the last dose of study drug. Male participants must also refrain from donating sperm during this period. Permitted methods that are at least 99% effective in preventing pregnancy should be communicated to the participant and his understanding confirmed.
b. Women of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test before the first dose on Day 1 and must agree to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from screening through safety follow-up. Permitted methods that are at least 99% effective in preventing pregnancy should be communicated to the participants and their understanding confirmed.
c. Women of nonchildbearing potential (ie, surgically sterile [hysterectomy, bilateral oophorectomy, or bilateral salpingectomy] OR postmenopausal, defined as ≥ 12 months of amenorrhea before screening without an alternative medical cause, confirmed by FSH levels at screening) are eligible. |
|
E.4 | Principal exclusion criteria |
1. Women who are currently pregnant or lactating.
2. Presence of > 20 draining fistulas at screening and baseline.
3. Participants with concurrent conditions or history of other diseases, as follows:
a. Any clinically significant medical condition other than HS, as determined by the investigator, that is not adequately controlled with appropriate treatment.
b. Any other active skin disease or condition (eg, bacterial, fungal, or viral infection) that may interfere with the course, severity, or assessments of HS.
c. Active systemic viral infection or any active viral infection that, based on the investigator's clinical assessment, make the participant an unsuitable candidate for the
study.
d. Current herpes zoster infection, a history of recurrent herpes zoster, a history of disseminated herpes simplex, or a history of herpes zoster.
e. History of or ongoing serious illness or medical, physical or psychiatric condition(s) that – in the investigator's opinion – would interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data.
f. Albinism.
4. Prolonged QT interval corrected for heart rate using Fridericia's formula (QTcF), defined as ≥ 450 msec.
Note: Prolonged QTcF values of ≥ 450 msec at screening are to be confirmed by performing 2 additional ECGs and averaging the results to determine whether the averaged value meets the exclusion criterion.
5. Positive test result for TB from the QuantiFERON-TB Gold test, or T-SPOT.TB test at screening (or, if two indeterminate tests, then as evaluated by a purified protein derivative test with a result of < 5 mm of induration within 3 months of screening).
6. A history of active TB (treated or untreated) or a history of untreated latent TB. Note: If the participant has possible evidence of a latent TB infection, the participant must have documented completion of an adequate course of therapy for latent TB and provide recent (within 3 months) posteroanterior and lateral view chest X-rays without
changes suggestive of active or latent TB, before baseline.
7. Positive serology test results for HIV, HBsAg, HBV core antibody, or HCV
(HCV-antibody with positive HCV-RNA) at screening.
8. Decreased blood cell counts at screening, defined as follows:
a. Leukocytes < 3.0 × 109/L (< 2.5 × 109/L for participants who are African-American).
b. ANC < 1.5 × 109/L.
c. Lymphocytes < 0.8 × 109/L.
d. Hemoglobin < 10 g/dL.
e. Platelets < 150 × 109/L.
9. Severely impaired liver function (Child-Pugh Class C) or ALT or AST levels
≥ 1.5 × ULN at screening.
10. Impaired renal function with serum creatinine > 1.5 mg/dL at screening.
11. Use of the following medications:
a. Previous use of JAK inhibitors, systemic or topical (eg, ruxolitinib, tofacitinib, baricitinib, filgotinib, lestaurtinib, and pacritinib).
b. Previous use of adalimumab or any other TNF-α treatment within 12 weeks or 5 half-lives (whichever is longer) before baseline.
c. Use of any investigational or experimental treatments within 12 weeks or 5 half-lives (whichever is longer) before baseline.
d. Systemic immunosuppressive or immunomodulating drugs (eg, oral or injectable corticosteroids, methotrexate, cyclosporine, and azathioprine) within 4 weeks or 5 half-lives (whichever is longer) before baseline.
e. Other systemic therapies for HS (eg, retinoids and antiandrogens) with potential therapeutic impact for HS within 4 weeks or 5 half-lives (whichever is longer) before baseline.
f. Surgical, laser, or IPL intervention in area with HS lesion within 4 weeks before baseline.
g. Systemic anti-infectives (eg, antibiotics, antivirals, antifungals) within 4 weeks, except as described in Section 6.7.1.1 for antibiotic therapy, or topical anti-infectives on HS lesions (eg, antibiotics, antivirals, antifungals) within 2 weeks before baseline.
h. Received live vaccine within 6 weeks before baseline or planning to receive live vaccine during the course of the study or within 6 weeks after EOT.
i. Topical antiseptic washes, creams, soaps, ointments, gels, and liquids containing antibacterial agents to treat HS, except those listed in Sections 6.7.1.3 and 6.7.1.4, within 2 weeks before baseline.
j. Potent systemic CYP3A4 inhibitors and inducers (see Study Manual) or fluconazole within 2 weeks or 5 half-lives (whichever is longer) before baseline. Note: Topical agents with limited systemic availability are permitted.
12. Known or suspected allergy to INCB054707 or any component of the study drug.
13. Known history of clinically significant drug or alcohol abuse in the last year before baseline.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Frequency, duration, and severity of AEs, clinical
laboratory test results, vital signs results, ECGs,
and physical examination findings. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
AEs: at each visit
clinical laboratory tests: at each visit
vital signs: at each visit
ECGs: at screening, Day 1, Week 4, week 8.
physical examination: at screening and Week 8. |
|
E.5.2 | Secondary end point(s) |
-Population PK parameters of INCB054707.
-Proportion of participants achieving a HiSCR at
each visit.
-Proportion of participants achieving an AN count
of 0 to 2 at each visit.
-Mean change from baseline in the HS Pain NRS
scores, worst and average pain, at each visit.
-Mean change from baseline to Week 8 in the
modified Sartorius scale score.
-Mean change from baseline in the number of
draining fistulas count at each visit.
-Proportion of participants at each category of
Hurley Stage at baseline and Week 8.
-Proportion of participants with change from
baseline in Hurley Stage at Week 8.
-Proportions of participants in each HS-PGIC
category during the treatment period.
-Actual measurements in HS-PGIC at each visit. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
PK: Day 1, Week 2, Week 4, Week 6, Week 8.
HiSCR, AN count: at each visit
HS pain NRS: at each visit
Sartorius scale score: Day 1, Week 8 and at follow-up
Fistulas count: at each visit
Hurley stage: at screening, Week 8 and at follow-up
HS-PGIC: At week 1,2,4,6,8 and at follow-up
Rescue lesional treatment: Week 1,2,4,6,8 and at follow-up
DLQI: at each visit |
|
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 | Yes |
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 | No |
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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 5 |
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 |
|
E.8.7 | Trial has a data monitoring committee | No |
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 |