Overview
The purpose of this phase 2 study is to evaluate the effect and the safety of the combination of ANIFROLUMAB in combination with phototherapy in adult participants with non-segmental progressive vitiligo
Description
Treatment Strategy: Multicentric, parallel double blind randomized phase 2 prospective study comparing ANIFROLUMAB (300mg/month) + narrowband UVB TL01 versus placebo + narrowband UVB TL01 Follow-up of the study: patients included in this study will start ANIFROLUMAB 3 months before starting narrowband UVB TL01. Phototherapy will be performed twice a week during 6 months. Follow-up visit will be done at week 12, 24, 36 and 48.
Eligibility
Inclusion Criteria:
- Subject: male or female aged ≥ 18 years and ≤ 65 years
- Subject with body weight ≥ 40kg
- Diagnosis of non-segmental (symmetrical) vitiligo with a body surface area involved >5% excluding hands and feet
- Active non-segmental vitiligo is defined by:
Non-segmental vitiligo with new patches or extension of old lesions during the last 6
months AND Presence of hypochromic aspect under Wood's lamp examination and/or
perifollicular hypopigmentation under Wood's lamp examination.
- Able to read, understand, and give documented (electronic or paper signature) informed
consent
- Registered in the French Social Security
- Agree to discontinue the use of the following excluded medications/treatments for at
least 4 weeks prior to randomization (Visit 2) and throughout the study: systemic
steroids, phototherapy, methotrexate, cyclosporine, mycophenolate mofetil, and
azathioprine.
- Agree to discontinue the use of the following excluded medications for at least 2
weeks prior to randomization (Visit 2) and throughout the study:
TCS or topical immune modulators (e.g., tacrolimus or pimecrolimus) Topical
phosphodiesterase type 4 (PDE-4) inhibitor (e.g. crisaborole) Topical JAK inhibitor (e.g.,
tofacitinib or ruxolitinib) and/or any other investigational topical treatments.
- Patient characteristics
- Are male or nonpregnant, nonbreastfeeding female patients:
1. Male patients must agree to use 2 forms of birth control (1 must be highly
effective, see below) while engaging in sexual intercourse with female partners
of childbearing potential while enrolled in the study and for at least 4 weeks
following the last dose of investigational product.
2. Female patients of childbearing potential must agree to use 2 forms of birth
control, when engaging in sexual intercourse with a male partner while enrolled
in the study and for at least 12 weeks following the last dose of investigational
product.
The following birth control methods are considered acceptable (the patient should
choose 2 to be used with their male partner, and 1 must be highly effective):
Highly effective birth control methods: oral, injectable, or implanted hormonal
contraceptives (combined estrogen/progesterone or progesterone only, associated
with inhibition of ovulation); intrauterine device (containing copper) or
intrauterine system (e.g., progestin-releasing coil); or vasectomized male (with
appropriate post vasectomy documentation of the absence of sperm in the
ejaculate). Effective birth control methods: condom with a spermicidal foam, gel,
film, cream, or suppository; occlusive cap (diaphragm or cervical/vault caps)
with a spermicidal foam, gel, film, cream, or suppository; or oral hormonal
contraceptives.
3. Females of non-childbearing potential are not required to use birth control and
they are defined as:
Women ≥60 years of age or women who are congenitally sterile, or Women ≥40 and <60 years of
age who have had a cessation of menses for ≥12 months and a folliculostimulating hormone
(FSH) test confirming non-childbearing potential (≥40 mIU/mL or ≥40 IU/L), or women who are
surgically sterile (i.e., have had a hysterectomy or bilateral oophorectomy or tubal
ligation).
- Patients fully vaccinated against COVID-19. A patient is considered fully vaccinated
≥2 weeks after receipt of the second dose in a 2-dose series (Pfizer-BioNTech and
Moderna).
- Signed informed consent form (ICF)
Exclusion Criteria:
General exclusion criteria
- Segmental or mixed vitiligo
- Patients that are currently experiencing or have a history of other concomitant skin
conditions (e.g., psoriasis or lupus erythematosus) that would interfere with
evaluations of the effect of study medication on vitiligo
- Patients who are currently experiencing a skin infection that requires treatment, or
who are currently being treated with topical or systemic antibiotics.
- Patients that have any serious concomitant illness that is anticipated to require the
use of systemic corticosteroids or otherwise interfere with study participation or
require active frequent monitoring. (e.g., unstable chronic asthma).
- Patients with history of basal cell or squamous epithelial skin cancer or melanoma
- Presence of significant uncontrolled neuropsychiatric disorder, are clinically judged
by the investigator to be at risk for suicide.
- Current alcohol, drug, or chemical abuse
Exclusion criteria related to concomitant medications
- Patients that have been treated with the following therapies:
1. monoclonal antibody (e.g., ustekinumab, omalizumab, dupilumab) for less than 5
half-lives prior to randomization.
2. received prior treatment with any oral JAK inhibitor (e.g., tofacitinib,
ruxolitinib)
3. received any systemic corticosteroid administered within 4 weeks prior to planned
randomization or are anticipated to require systemic corticosteroids during the
study.
4. received any systemic treatment with Methotrexate, Azathioprine, Cyclosporine
within 12 weeks prior to planned randomization
5. have had an intra-articular corticosteroid injection within 4 weeks prior to
planned randomization.
6. have received more than 250 UV lights sessions
- Patients that are largely or wholly incapacitated permitting little or no self-care,
such as being bedridden.
Exclusion criteria related to infection and malignancy risk factors
- Any underlying condition that predisposes the subject to infection, including history
of/current human immunodeficiency virus (HIV) infection
- An HIV test must be performed. The result should be available within 30 days of
randomisation, but prior to the second dose of investigational product administration
(Visit 2/Week 4).
Confirmed positive test for hepatitis B serology for:
1. Hepatitis B surface antigen, OR
2. Hepatitis B core antibody (HBcAb) AND hepatitis B virus (HBV) DNA detected above the
lower limit of quantitation Note: Patients who were HBcAb positive at screening were
tested every 3 months for HBV DNA. To remain eligible for the study, the patient's HBV
DNA levels must have remained below the limit of quantitation
- Positive test for hepatitis C antibody
- Any of the following:
1. Clinically significant chronic infection (ie, osteomyelitis, bronchiectasis,
etc) within 8 weeks prior to Inclusion Visit (chronic nail infections not
causing open skin lesions are allowed)
2. Any infection requiring hospitalisation or treatment with IV anti-infectives
not completed at least 4 weeks prior to Inclusion visit
- Any infection requiring IV or oral anti-infectives (including antivirals) within
2 weeks prior to Inclusion visit
- Have evidence of active TB or latent TB:
1. have evidence of active TB, defined in this study as the following:
Documented by a positive PPD test (≥5 mm induration between approximately 48
and 72 hours after application, regardless of vaccination history), medical
history, clinical features, and abnormal chest x-ray at screening. The
QuantiFERON®-TB Gold test or TSPOT®.TB test (as available and if compliant
with local TB guidelines) may be used instead of the PPD test. Patients are
excluded from the study if the test is not negative and there is clinical
evidence of active TB.
Exception: Patients with a history of active TB who have documented evidence
of appropriate treatment, have no history of re-exposure since their
treatment was completed, and have a screening chest x-ray with no evidence
of active TB may be enrolled if other entry criteria are met. Such patients
would not be required to undergo the protocol-specific TB testing for PPD,
QuantiFERON®-TB Gold test, or T-SPOT® TB test but must have a chest x-ray at
screening.
2. have evidence of untreated/inadequately or inappropriately treated latent
TB, defined in this study as the following: documented to have a positive
PPD test (≥5 mm induration between approximately 48 and 72 hours after
application, regardless of vaccination history), no clinical features
consistent with active TB, and a chest x-ray with no evidence of active TB
at screening; or PPD test is positive and the patient has no medical history
or chest x-ray findings consistent with active TB, the patient may have a
QuantiFERON®-TB Gold test or TSPOT® TB test (as available and if compliant
with local TB guidelines). If the test results are not negative, the patient
will be considered to have latent TB (for purposes of this study); or
QuantiFERON®-TB Gold test or T-SPOT® TB test (as available and if compliant
with local TB guidelines) may be used instead of the PPD test. If the test
results are positive, the patient will be considered to have latent TB. If
the test is not negative, the test may be repeated once within approximately
2 weeks of the initial value. If the repeat test results are again not
negative, the patient will be considered to have latent TB (for purposes of
this study). Exception: Patients who have evidence of latent TB may be
enrolled if he or she completes at least 4 weeks of appropriate treatment
prior to randomization and agrees to complete the remainder of treatment
while in the trial.
Exception: Patients with a history of latent TB who have documented evidence of appropriate
treatment, have no history of re-exposure since their treatment was completed, and have a
screening chest x-ray with no evidence of active TB may be enrolled if other entry criteria
are met.
Such patients would not be required to undergo the protocol specific TB testing for PPD,
QuantiFERON®-TB Gold test, or TSPOT® TB test but must have a chest x-ray at screening.
- Safety exclusions labs
- At Screening (within 4 weeks before Week 0 [Day 1]), any of the following:
1. Aspartate aminotransferase (AST) >2.0 × upper limit of normal (ULN).
2. Alanine aminotransferase (ALT) >2.0 × ULN.
3. Total bilirubin >1.5ULN (unless due to Gilbert's syndrome)
4. Serum creatinine >2.0 mg/dL (or >181 μmol/L)
5. Neutrophil count <1000/μL (or <1.0 × 109/L)
6. Platelet count <25000/μL (or <25 × 109/L)
7. Haemoglobin <8 g/dL (or <80 g/L),
8. Glycosylated haemoglobin (HbA1c) >8% (or >0.08) at screening (diabetic subjects
only) Note: Abnormal screening laboratory tests may be repeated ONCE on a
separate sample before subject is declared a screen failure.
- Confirmed COVID-19: The Baseline Visit must be at least 14 days from onset of
signs/symptoms or positive SARS-CoV-2 test; symptomatic subjects must have recovered,
defined as resolution of fever without use of antipyretics and improvement in
symptoms;
- Suspected COVID-19: Subjects with signs/symptoms suggestive of COVID-19, known
exposure, or high risk behavior should undergo molecular (e.g., polymerase chain
reaction [PCR]) testing to rule out SARS-CoV-2 infection or must be asymptomatic for
14 days from a potential exposure. Perioperative management of investigational product
Surgery should be avoided during the study if clinically feasible, but is permitted.
If a surgery becomes necessary during the study, it should be scheduled at least 4
weeks after the previous administration of investigational product.
For non-major surgery, the decision to withhold investigational product administration is
at the Investigator's discretion.
For major surgery, investigational product administration can be resumed at the
Investigator's discretion after all of the following criteria are met:
- External wound healing is complete, and
- Any postoperative antibiotic course is completed, and
- All acute surgical complications have resolved Blood donations Subjects should not
donate whole blood, blood components or sperm until the completion of the follow-up
period.
Other non-inclusion criteria
- Have hypersensitivity to anifrolumab or to any of the excipients.
- Are unable or unwilling to make themselves available for the duration of the study
and/or are unwilling to follow study restrictions/procedures.
- Are currently enrolled in any other clinical trial involving an investigational
product or any other type of medical research judged not to be scientifically or
medically compatible with this study.
- Have participated within the last 30 days in a clinical study involving an
investigational product. If the previous investigational product has a long half-life
(2 weeks or longer), at least 3 months or 5 half-lives (whichever is longer) should be
allowed between the end of the previous treatment and the inclusion.
- Have previously been randomized in this study or any other study investigating
anifrolumab.
- Are investigator site personnel directly affiliated with this study and/or their
immediate families. Immediate family is defined as a spouse, parent, child, or
sibling, whether biological or legally adopted.