| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| MODERATE TO SEVERE ALOPECIA AREATA IN ADULT PATIENTS |
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| E.1.1.1 | Medical condition in easily understood language |
| EPISODE OF HAIR LOSS ASSOCIATED WITH ALOPECIA AREATA IN ADULT PATIENTS |
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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 | PT |
| E.1.2 | Classification code | 10001761 |
| E.1.2 | Term | Alopecia areata |
| E.1.2 | System Organ Class | 10040785 - Skin and subcutaneous tissue disorders |
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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 |
The overall objectives of the study are to assess the efficacy and safety following administration of CTP-543 in adult patients with moderate to severe alopecia areata.
The primary objectives of the study are to assess:
•The efficacy of CTP-543 on regrowth of hair following 24 weeks of treatment
•The safety of CTP-543 following 24 weeks of treatment.
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| E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are to assess:
•Clinician- and patient-reported impression of the severity and improvement of alopecia areata
•Patient-reported satisfaction with their scalp hair
•Patient-reported levels of anxiety and depression
•Changes in eyebrows and eyelashes.
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Written informed consent, and authorization for release and use of protected health information.
2. Between 18 and 65 years of age, inclusive, at the time of informed consent.
3. Definitive diagnosis of alopecia areata with a current episode of scalp hair loss lasting at least 6 months and not exceeding 10 years at the time of Screening. Total disease duration greater than 10 years is permitted.
4. At least 50% scalp hair loss, as defined by a SALT score ≥50, at Screening and Baseline.
5. Female subjects are eligible to participate if at least one of the following conditions applies:
a)Is a woman of childbearing potential (WOCBP) and using a medically highly effective form of birth control with a failure rate less than 1% per year from at least 4 weeks prior to Baseline until at least 30 days following last dose of study drug. Examples of medically highly effective birth control methods include:
i. Combined (estrogen and progestogen containing) hormonal contraception (oral, patch, vaginal ring)
ii. Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable)
iii. Intrauterine device or intrauterine hormone-releasing system
iv. Bilateral tubal occlusion
v. Vasectomized partner (partner is the sole sexual partner of the WOCBP trial participant and the vasectomized partner has received medical assessment of the surgical success)
vi. Sexual abstinence (reliable as refraining from heterosexual intercourse during the above-mentioned period)
b) Is not a WOCBP:
i. Premenopausal with one of the following:
a. Documented hysterectomy;
b. Documented bilateral salpingectomy;
c. Documented bilateral oophorectomy.
ii. Postmenopausal (cessation of menses for at least 12 months prior to screening)
Postmenopausal is defined as no menses for 12 months without an alternative medical cause. In addition, a high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm postmenopausal in women under 60 years old and not using hormonal contraception or hormone replacement therapy (HRT). However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient. Females on HRT and whose menopausal status is in doubt will be required to use one of the nonestrogen hormonal highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of postmenopausal status before study enrollment
6. Male participants must:
a. Agree to use, with their partners, male contraception (condom) and one of the highly effective contraceptive methods listed in Inclusion Criterion 5, from Baseline until at least 90 days following last dose of study drug.
b. Refrain from donating sperm during the study and for at least 90 days after the end of the study.
7. Willing to comply with the study visits and requirements of the study protocol.
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1. Írásos tájékoztatás utáni beleegyezés, valamint engedély a védett egészségügyi adatok kiadására és felhasználására.
2. A tájékoztatás utáni beleegyezés időpontjában 18 és 65 év közötti életkor, a szélső értékeket is beleértve.
3. Az alopecia areata egyértelmű diagnózisa a fejbőr hajhullásának jelenlegi epizódjával, amely legalább 6 hónapja tart, és a szűrés időpontjában nem haladhatja meg a 10 évet. A betegség 10 évnél hosszabb teljes időtartama megengedett.
4. Legalább 50%-os fejbőr hajhullás, azaz a SALT pontszám ≥50 a szűréskor és a kiinduláskor.
5. A női alanyok akkor alkalmasak a részvételre, ha az alábbi feltételek közül legalább egy teljesül:
a) Fogamzóképes nő (women of childbearing potential, WOCBP) és orvosilag nagyon hatékony fogamzásgátló módszert használ, amelynél a hibaarány kevesebb mint 1% évente, a kiindulás előtti legalább 4. héttől kezdve a vizsgálati készítmény utolsó adagja utáni legalább 30 napig. Példák az orvosilag nagyon hatékonynak számító fogamzásgátló módszerekre:
i. Kombinált (ösztrogént és progesztogént tartalmazó) hormonális fogamzásgátlás (orális, tapasz, hüvelygyűrű)
ii. Csak progesztogént tartalmazó hormonális fogamzásgátlás az ovuláció gátlásával (orális, injekció, implantátum)
iii. Méhen belüli eszköz vagy méhen belüli hormonkibocsátó rendszer
iv. Kétoldali petevezeték-elzárás
v. Vazektomizált partner (a partner a WOCBP vizsgálati résztvevő egyedüli szexuális partnere, és a műtét sikerét orvosi szempontból értékelték a vazektomizált partnernél)
vi. Szexuális absztinencia (megbízható abban, hogy tartózkodik a heteroszexuális közösüléstől a fent említett időszak alatt)
b) Nem WOCBP:
i. Premenopauza az alábbiak egyikével:
a. Dokumentált hiszterektómia;
b. Dokumentált kétoldali szalpingektómia;
c. Dokumentált kétoldali petefészek-eltávolítás.
ii. Posztmenopauzában van (a szűrés előtt legalább 12 hónapja nem menstruál)
A posztmenopauza úgy határozható meg, hogy 12 hónapja nem jelentkezett menstruáció, és ennek nincs más orvosi oka. Ezenkívül a posztmenopauzális tartományban lévő magas follikulus stimuláló hormon (FSH) szint használható a posztmenopauza megerősítésére 60 év alatti nőknél, akik nem alkalmaznak hormonális fogamzásgátlást vagy hormonpótló terápiát (hormon replacement therapy, HRT). Azonban 12-hónapos amenorrhea hiányában egyetlen FSH mérés nem elegendő. A HRT-t alkalmazó nőknek, akiknek a menopauzális státusza kétséges, az ösztrogént nem tartalmazó hormonális, nagy hatékonyságú fogamzásgátló módszerek egyikét kell alkalmazniuk, ha a HRT-t a vizsgálat során folytatni kívánják. Egyébként abba kell hagyniuk a HRT-t, hogy lehetővé tegyék a posztmenopauzális státusz megerősítését a vizsgálatba való bevonás előtt.
6. A férfi résztvevőknek kötelezően:
a. Bele kell egyezniük, hogy partnereikkel férfi fogamzásgátlást (óvszert) és az 5. beválasztási kritériumban felsorolt nagy hatékonyságú fogamzásgátló módszerek egyikét alkalmazzák a kiindulástól a vizsgálati készítmény utolsó adagja után legalább 90 napig.
b. Tartózkodniuk kell a spermaadományozástól a vizsgálat ideje alatt és a vizsgálat vége után még legalább 90 napig.
7. Hajlandó betartani a vizsgálati viziteket és a vizsgálati protokoll követelményeit.
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| E.4 | Principal exclusion criteria |
1.History or presence of hair transplants.
2.Treatment with other medications or agents within 1 month of Baseline or during the study that may affect hair regrowth or immune response, including but not limited to: corticosteroids administered orally, intravenously or intramuscularly, or applied to areas of skin affected by alopecia (intranasal and inhaled corticosteroids are allowed, eye and ear drops containing corticosteroids are also allowed); oral retinoids, oral cyclines (minocin, tetracycline); platelet-rich plasma injections; topical application to affected areas of retinoids, anthralin, squaric acid, diphenylcyclopropenone, or minoxidil.
3.Treatment with systemic immunosuppressive medications including but not limited to methotrexate, cyclosporine, azathioprine, chloroquine derivatives, etanercept, JAK inhibitors within 3 months of Screening or during the study.
4.Treatment with biologics (e.g., adalimumab, atlizumab, canakinumab, certolizumab, fontolizumab, golimumab, infliximab, mepolizumab, rituximab, secukinumab, tocilizumab, ustekinumab) within 6 months of Screening or during the study.
5.Active scalp inflammation, psoriasis, or seborrheic dermatitis requiring topical treatment to the scalp, significant trauma to the scalp, or other scalp condition that may interfere with the SALT assessment, or untreated actinic keratosis anywhere on the body at Screening and/or Baseline.
6.Known history of moderate to severe androgenic alopecia or female pattern hair loss prior to alopecia areata.
7.Unwilling to maintain a consistent hair style, including shampoo and hair products (including hair dye, process, and timing to hair appointments), and to refrain from weaves or extensions throughout the course of the study, or shaving of scalp hair for 2 weeks preceding a SALT assessment.
8.Use of adhesive wigs, other than banded perimeter wigs, during the study.
9.History of a lymphoproliferative disease or malignancy, other than non-melanoma skin cancer or cervical carcinoma. Patients with 3 or more basal or squamous cell carcinomas diagnosed in the past 2 years are excluded.
10.History of solid organ or hematological transplantation.
11.Fever, inflammation, or systemic signs of illness suggestive of systemic or invasive infection or a positive SARS-CoV-2 test result within 2 weeks prior to Baseline.
12.Abnormal levels of thyroid stimulating hormone at Screening, defined as <0.9 x the lower limit of normal (LLN) and >1.5 x the upper limit of normal (ULN).
13.Screening labs outside the normal range for parameters associated with potential risk for treatment under investigation. This will include but is not limited to:
a.Platelets ≤100 x 109/L or ≥ 600 x 109/L
b.Absolute neutrophil count ≤1.5 x 109/L
c.Hemoglobin levels ≤10.5 g/dL for females, or hemoglobin levels ≤12.0 g/dL for males
14.Screening blood level of hemoglobin A1c ≥7.5% (58 mmol/mol, 9.3 mmol/L).
15.Abnormal liver function at Screening, defined as ≥2 × ULN of serum alanine transaminase, serum aspartate transaminase, and serum alkaline phosphatase, or ≥1.5 x ULN total bilirubin (unless isolated Gilbert’s syndrome).
16.Abnormal renal function (estimated glomerular filtration rate <60 mL/min/1.73 m2 using the CKD-EPI 2009 equation) at Screening.
17.Patient has positive results for hepatitis B surface antigens (HBsAg), antibodies to hepatitis B core antigens (anti-HBc), or hepatitis C virus (HCV) at Screening, or known history of human immunodeficiency virus infection. Subjects who test positive for HCV but who are in remission (sustained virologic response as evidenced by undetectable HCV RNA level using a sensitive assay≥ 12 weeks after completion of HCV therapy) are allowed inclusion in the study.
18.Vaccination with a live attenuated vaccine during the study or up to 6 weeks prior to randomization.
19.History of previous active disease due to M. tuberculosis (TB) without documentation of successful treatment; OR, patient has a positive result from a Tuberculin Skin Test (TST) or a QuantiFERON-TB Gold (QFT) test performed at Screening.
20.History of prolonged QT syndrome or a Screening QTc interval with Fridericia’s correction (QTcF) > 450 msec for males or QTcF > 470 msec for females.
21.History of alcohol, medication, or illicit drug abuse within 1 year before the first dose of study drug.
22.Females who are nursing, pregnant, or planning to become pregnant while in the study, and for 30 days after last dose of study drug.
23.Participation in another investigational study within the greater of 4 weeks or 5 half-lives of an investigational medication prior to screening or during the study.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| •The primary efficacy endpoint will be the percentage of patients achieving an absolute SALT score ≤20 at Week 24. |
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
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| E.5.2 | Secondary end point(s) |
•Percentage of responders (defined as “satisfied” or “very satisfied”) on the Hair Satisfaction Patient Reported Outcome (SPRO) scale at Week 24
•Percentage of patients achieving an absolute SALT score of ≤20 at Week 20, 16, 12 and 8
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
at week 8, 12, 16, 20 and 24
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| 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 | No |
| 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 | 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) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| 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
| 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 | 30 |
| 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 |
| France |
| Germany |
| Hungary |
| Poland |
| Spain |
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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
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| 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 | |
| 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 |
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