| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
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| E.1.1.1 | Medical condition in easily understood language |
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| E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
| 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 |
| To evaluate the efficacy of PF-06651600 compared to placebo in adult and adolescent alopecia areata (AA) subjects with 50% or greater scalp hair loss on regrowth of lost hair (as measured by an absolute Severity of Alopecia Tool (SALT) Score ≤10) at Week 24. |
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| E.2.2 | Secondary objectives of the trial |
• To characterize the exposure response of PF-6651600 on regrowth of lost hair.
• To assess the efficacy of PF-06651600 on regrowth of lost hair during the treatment period over time.
• To evaluate the effect of PF-06651600 on patient-centered outcomes and payer relevant measures to assess treatment benefit from the patient perspective and to demonstrate value. |
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
| Banked biospecimens, amendment 2, 30 May 2019 |
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| E.3 | Principal inclusion criteria |
1.Evidence of a personally signed and dated informed consent document indicating that the subject or a legally acceptable representative/parent(s)/legal guardian has been informed of all pertinent aspects of the study.
2.Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
3.Male or female subjects age 12 years and older, inclusive, at time of informed consent/assent. Adolescent subjects below the age of 18 years will only be enrolled into this study if permitted by the sponsor, local competent authority, and institutional review board (IRB)/ethics committee (EC). Otherwise, only subjects 18 years or older (or age specified by applicable reviewer) will be enrolled in those countries, regions, or sites. Within the EU, subjects must be aged 18 through 74 years at the time of informed consent.
4.Subjects must meet/comply with the following reproductive criteria:
Females:
Female subjects are eligible to participate if they are not pregnant or breastfeeding, and at least 1 of the following conditions applies:
a.Is a woman of childbearing potential (WOCBP) and using a contraceptive method that is highly effective (with a failure rate of <1% per year), as described in Section 4.3, during the intervention period and for at least 28 days after the last dose of study intervention. The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention.
OR
b.Is not a WOCBP (see definitions below):
Women in the following categories are not considered WOCBP:
•Premenarchal.
•Premenopausal female with 1 of the following:
•Documented hysterectomy;
•Documented bilateral salpingectomy;
•Documented bilateral oophorectomy.
For individuals with permanent infertility due to an alternate medical cause other than the above, (eg, Müllerian agenesis, androgen insensitivity), investigator discretion should be applied to determining study entry.
Note: Documentation for any of the above categories can come from the site personnel’s review of the participant’s medical records, medical examination, or medical history interview. The method of documentation should be recorded in the participant’s medical record for the study.
•Postmenopausal female:
A postmenopausal state 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 must be used to confirm a postmenopausal state in women under 60 years old and not using hormonal contraception or hormone replacement therapy (HRT). 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.
The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy. Documentation of this review should be included in the participant’s medical record for the study.
Males:
Outside of VHP countries in the EU, no contraceptive methods are required for male subjects in this study.
Within VHP countries in the EU, male subjects are eligible to participate if they agree to the following requirements during the intervention period and for at least 90 days after the last dose of study intervention:
•Refrain from donating sperm AND
•Use one acceptable method of contraception as described in Section 4.3.
5.Must meet the following AA criteria:
a.Have a clinical diagnosis of AA with no other etiology of hair loss (eg, telogen effluvium, androgenetic alopecia, etc.).
b.50% hair loss of the scalp, including alopecia totalis (AT) and alopecia universalis (AU), without evidence of terminal hair regrowth within 6 months at both the screening and baseline visits.
•AT is defined as complete (100%) scalp hair loss.
•AU is defined as complete (100%) scalp, facial, and body hair loss.
•Percentage of hair loss on the scalp will be measured by SALT (Appendix 5).
•Photographs taken at Screening must be submitted to the Sponsor or designee for verification of SALT score ≥50 and hair loss due to AA. Subjects must not be randomized until verification has been confirmed.
c.Current episode of hair loss ≤10 years.
6.If receiving permitted concomitant medications for any reason other than AA, subjects should be on a stable regimen, which is defined as not starting a new drug or changing dosage within 7 days or 5 half lives (whichever is longer) prior to Day 1. Subject must be willing to stay on a stable regimen during the duration of the study (see Section 5.8 of the protocol).
Please see the Protocol for a complete list of inclusion criteria. |
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| E.4 | Principal exclusion criteria |
1. Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or subjects who are Pfizer employees, including their family members, directly involved in the conduct of the study.
2. Participation in other studies involving investigational drug(s) within 8 weeks or within 5 half-lives (if known), whichever is longer, prior to study entry and/or during study participation.
3. Other types of alopecia (including, but not limited to traction and scarring alopecia, telogen effluvium). Subjects with known androgenetic alopecia will be excluded.
4. Other scalp disease that may impact AA assessment (eg, scalp psoriasis, dermatitis, etc).
5. Active systemic diseases that may cause hair loss (eg, lupus erythematosus, thyroiditis, systemic sclerosis, lichen planus, etc).
6. Any psychiatric condition including recent or active suicidal ideation or behavior that meets any of the following criteria:
a. Suicidal ideation associated with actual intent and a method or plan in the past year: “Yes” answers on items 4 or 5 of the Columbia Suicide Severity Rating Scale (C SSRS) (Appendix 6).
b. For subjects who had previous history of suicidal behaviors in the past >1 year to <5 years: “Yes” answer (for events that occurred in the past 5 years) to any of the suicidal behavior items of the C SSRS or any lifetime history of serious or recurrent suicidal behavior, a risk assessment must be performed, and documented, by a qualified mental health professional to assess whether it is safe for the subject to participate in the trial.
c. Clinically significant depression as indicated by a Patient Health Questionnaire - 8 Items (PHQ 8) (Appendix 13) total score ≥15.
d. The presence of any current major psychiatric disorder that is not explicitly permitted in the inclusion/exclusion criteria.
NOTE: For any subject who has significant depression or any suicidal behavior, the subject will not be randomized and should be referred for appropriate evaluation and treatment.
7.Have hearing loss with progression over the previous 5 years, or sudden hearing loss, or middle or inner ear disease such as otitis media, cholesteatoma, Meniere’s disease, labyrinthitis, or other auditory condition that is considered acute, fluctuating or progressive.
Please see the Protocol for a complete list of exclusion criteria. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| • Response based on an absolute SALT Score ≤10 at Week 24. |
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
• Response based on an absolute SALT Score ≤10 at Week 24 will be used to characterize the exposure response of PF-06651600 on regrowth of lost hair.
Secondary endpoints to assess the efficacy of PF-06651600 on regrowth of lost hair during the treatment period over time:
• Response based on a SALT score of ≤10 at Weeks 4, 8, 12, 18, 28, 34, 40, and 48.
• Response based on a 50% improvement in SALT score from baseline (SALT50) at Weeks 4, 8, 12, 18, 24, 28, 34, 40, and 48.
• Response based on a 75% improvement in SALT score from baseline (SALT75) at Weeks 4, 8, 12, 18, 24, 28, 34, 40, and 48.
• Response based on a 90% improvement in SALT score from baseline (SALT90) at Weeks 4, 8, 12, 18, 24, 28, 34, 40, and 48.
• Absolute SALT scores at Baseline, Weeks 4, 8, 12, 18, 24, 28, 34, 40, and 48.
• Response based on at least a 2 grade improvement or a score of 3 in Eyebrow Assessment (EBA) score at Weeks 4, 8, 12, 18, 24, 28, 34, 40, and 48.
• Response based on at least a 2 grade improvement or a score of 3 in Eyelash Assessment (ELA) score at Weeks 4, 8, 12, 18, 24, 28, 34, 40, and 48.
Secondary endpoints based to evaluate the effect of PF-06651600 on patient-centered outcomes and payer relevant measures to assess treatment benefit from the patient perspective and to demonstrate value:
• Change from baseline in Alopecia Areata Patient Priority Outcomes (AAPPO) scale total score, hair loss domain score, and psychological and functional impact domain score at Weeks 4, 8, 12, 18, 24, 34, 40, and 48.
• Change from baseline in the depression and anxiety scales of the Hospital Anxiety and Depression Scale (HADS) at Weeks 4, 8, 12, 24, and 48.
• Change from baseline in 36-Item Short Form Health Survey version 2 Acute (SF36v2 Acute) at Weeks 4, 8, 12, 24, and 48.
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Various timepoints for each secondary endpoints are defined within the endpoint |
|
| 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 | Yes |
| E.6.12 | Pharmacoeconomic | Yes |
| 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) | 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 | Yes |
| E.8.1.7.1 | Other trial design description |
|
| 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 | 7 |
| 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 | 38 |
| 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 |
| Argentina |
| Australia |
| Canada |
| Chile |
| China |
| Colombia |
| Czech Republic |
| Germany |
| Hungary |
| Japan |
| Korea, Republic of |
| Mexico |
| Poland |
| Russian Federation |
| Spain |
| Taiwan |
| United Kingdom |
| United States |
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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 | 1 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | 29 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 1 |
| E.8.9.2 | In all countries concerned by the trial days | 4 |
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