| 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 |
| Acneiform rash is characterized by tender erythematous papules, which after a few days evolve into pustules and then into crusts. It affects skin areas with a high density of sebaceous glands. |
|
| 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 | 21.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10037847 |
| E.1.2 | Term | Rash acneiform |
| 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 assess the efficacy of ANB019 compared with placebo in reduction of acneiform rash symptoms in subjects receiving EGFRi or MEKi therapy as measured by facial inflammatory lesion count. |
|
| E.2.2 | Secondary objectives of the trial |
• To determine the effect of ANB019 compared with placebo on acneiform
rash signs and symptoms, and quality of life in subjects receiving EGFRi
or MEKi therapy
• To assess the safety and tolerability of ANB019 in subjects with
acneiform rash receiving EGFRi or MEKi therapy |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Male and female subject aged 18 to 75 years (inclusive) at the time of signing the informed consent.
2. Subject has histologically confirmed cancer.
3. Subject is treated with an oral or injectable commercially-available EGFRi or MEKi therapy (alone or in
combination). Note: EGFRi or MEKi therapy must be started within 12 weeks prior to Day 1.
4. Subject has EGFRi/MEKi-related acneiform rash of Grade ≥ 2 as per CTCAE Version 5.0, and ≥ 20
inflammatory lesions on the face at screening and Day 1.
5. Subject has an ECOG performance score between 0 and 2.
6. Subject has a life expectancy of ≥ 6 months at Day 1.
7. Subject meets the following laboratory criteria at screening:
a) Hemoglobin ≥ 90 g/L (≥ 9 g/dL);
b) White blood cell count ≥ 3.0 × 109/L (≥ 3.0 × 103/µL);
c) Platelets ≥ 100 × 109/L (≥ 100 × 103/µL);
d) Serum creatinine ≤1.5 × upper limit of normal (ULN) and creatinine clearance ≥ 50 mL/min;
e) ALT and AST ≤ 2.5 × ULN with no liver metastases and ≤ 5 x ULN in presence of liver
metastases;
f) Total bilirubin ≤ 1.5 × ULN. Subjects with known Gilbert’s disease who have serum
bilirubin < 3 × ULN may be included;
g) Absolute Neutrophils Count > 1.5 × 103/µL.
Note: Due to the enrollment of immunocompromised subjects in the study whose laboratory
normal ranges may be greatly variable compared to other conditions, the final determination of
eligibility based on laboratory parameters may be done after Investigator assessment following
consultation with the Medical Monitor and Sponsor.
8. Subject has a body mass index (BMI) within the range of 18 to 38 kg/m2, inclusive {BMI = weight
(kg)/[height (m)]2}.
9. Subject has no clinically significant medical condition (other than cancer) or
physical/laboratory/ECG/vital signs abnormality that would, in the opinion of the Investigator, put
the subject at undue risk or interfere with interpretation of study results.
10.Contraceptive use by men and women should be consistent with local regulations regarding the
methods of contraception for those participating in clinical studies.
Contraception and pregnancy:
a) A male subject must agree to use contraception as detailed in Appendix 1 of this protocol
during the treatment period and for at least 220 days (which includes the duration of
relevant exposure plus the duration of sperm cycle) after the last study treatment
administration and refrain from donating sperm during this period.
b) Female subjects:
i. A woman of childbearing potential (WOCBP) is eligible to participate if she has a
negative serum pregnancy test (beta-human chorionic gonadotropin) at screening
and a negative urine pregnancy test at Day 1 (see Appendix 1), is not breastfeeding,
and agrees to follow the contraceptive guidance in Appendix 1 during the
treatment period and for at least 6 months after receiving the study treatment and
refrains from donating oocytes for assisted reproduction during this period. The
female subject’s selected form of contraception must be effective by the time the
female subject enters into the study at Day 1 (eg, hormonal contraception should
be initiated at least 48 days before Day 1). For WOCBP, hormonal contraceptives must be used on a stable regimen during the study treatment. Starting hormonal contraceptives during the study is not permitted.
Note: Drospirenone, chlormadinone acetate, or cyproterone acetate must be initiated and used on a stable regimen at least 26 weeks prior to Day 1.
ii. A woman not of childbearing potential, as defined in Appendix 1, must have a
follicle-stimulating hormone (FSH) test confirming nonchildbearing potential.
11.Subject is willing to participate and is capable of giving written informed consent, which must be personally signed and dated by the subject and obtained prior to any study-related activities.
12.Subject must be willing to comply with all study procedures and must be available for the duration
of the study |
|
| E.4 | Principal exclusion criteria |
1.Subject has infected EGFRi/MEKi-associated acneiform rash
2. Subject has other malignancies or medical conditions which may interfere with the ability to evaluate the subject’s response to therapy
3. Subject has significant skin disease other than EGFRi/MEKi-induced acneiform rash
4. Subject has a history of clinically significant cardiac, pulmonary, neurologic, gastrointestinal, endocrine, hematological, renal, hepatic, cerebral or psychiatric disease, or other major uncontrolled disease
5. Subject has a history of chronic or recurrent infectious disease within 6 months prior to screening
6. Subject has a history of a serious infection that led to hospitalization or treatment with IV antibiotics or antiviral treatment for an infection within 3 months prior to screening or any recent infection requiring systemic antibiotic within 1 week of Day 1, or systemic antiviral treatment within 4 weeks of Day 1
7. Subject has a history or any evidence of active that required systemic antibiotics within 1 week of Day 1 or other systemic treatment within 4 weeks of Day 1
8. Subject has any factors that would predispose the subject to develop an infection
9. Subject has a history of an opportunistic infection within 6 months prior to screening
10.Subject has a history of a herpes zoster infection within 2 months prior to screening
11.Subject has a known or suspected autoimmune disorder for which a subject requires medical follow-up or medical treatment
12.Subject has any history of known or suspected congenital or acquired immunodeficiency state, or condition that would compromise the subject’s immune status not related to their cancer diagnosis or treatment
13.Subject had any major surgery within 2 weeks of Day 1
14.Subject has a history of any significant drug allergy or reaction and reactivity to polysorbate 20, a component of ANB019 formulation, or the inactive ingredients
15.Subject has taken the following drugs within the specified period prior to Day 1:
a) an over-the-counter (OTC) topical medication for the treatment of acne, including topical anti-inflammatory medications, corticosteroids, or antibacterial/antiseptic soap or wash within 1 week prior to Day 1
b) prescription topical retinoid or other prescription topical medications for the treatment of acne within 4 weeks prior to Day 1, or antimicrobials within 1 week prior to Day 1
c) systemic antibiotics within 1 week prior to Day 1
d) topical agents or systemic agents that could affect pruritus within 2 weeks prior to Day 1
e) other systemic antiacne drugs not mentioned in other exclusion criteria within 4 weeks prior to Day 1
f) oral or injectable corticosteroids within 4 weeks prior to Day 1 or require them during the study
g) a facial procedure within 8 weeks prior to Day 1
h) photodynamic therapy or phototherapy with blue or red light within 12 weeks prior to Day 1
i) androgen receptor blockers within 12 weeks prior to Day 1
j) live attenuated vaccine within 12 weeks prior to Day 1
k) drospirenone, chlormadinone acetate, or cyproterone acetate on an unstable dose and frequency within 26 weeks prior to Day 1
l) oral retinoid or vitamin A supplements >10,000 U/d within 12 weeks prior to Day 1
m) nonbiological investigational drug to treat cancer within 2 weeks prior to Day 1, or any other nonbiological investigational drug within 4 weeks or 5 half-lives prior to Day 1
n) marketed or investigational biological agent to treat cancer within 2 weeks prior to Day 1, or any other marketed or investigational biological agent within 12 weeks or 5 half-lives prior to Day 1
o) Subject has had previous treatment with anti-IL-36R, anti-IL-36, anti-tumor necrosis factor (TNF)/IL-12/IL-23/IL-17, or any other mAbs within 12 weeks or 5 half-lives prior to Day 1
16.Subject has had excessive sun exposure or has used tanning booths within 4 weeks prior to Day 1
17.Subject has a history of active TB or latent TB infection at screening or within 6 months prior to screening, chest X-ray, and/or clinical examination, or has had active TB disease at any time in the past
18.Subject has a known history of clinically significant drug or alcohol abuse in the last year prior to Day 1
19.Subject is a pregnant or lactating woman
20.Subject has any other physical, mental, or medical conditions, which make study participation inadvisable or could confound study assessments
21.Subject has clinically significant abnormality on chest X-ray at screening, or on chest X-ray or any other chest imaging within 6 months prior to screening
22.Subject has any clinically significant abnormalities on 12-Lead ECG at screening
23.Subject has a positive blood screen for hepatitis C antibody, antibodies to hepatitis B core antigens, hepatitis B surface antigen, or human immunodeficiency virus 1 and 2 antibodies
24.Subject is not able to tolerate SC drug administration |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Change from Baseline in facial inflammatory lesion count (papules and pustules) at Week 8 |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
• Percent change from Baseline in facial inflammatory lesion count (papules and pustules) at Week 8
• Proportion of subjects with an improvement of at least 1 grade from Baseline in acneiform rash CTCAE grading scale at Week 8
• Time to first response of 1 grade improvement from Baseline on the acneiform rash CTCAE grading scale
• Proportion of subjects with an improvement of at least 1 grade from Baseline in acneiform rash modified MESTT grading scale (total score) at Week 8
• Time to first response of 1 grade improvement from Baseline on the acneiform rash modified MESTT grading scale (total score)
• Proportion of subjects with an improvement of at least 1 grade from Baseline in acneiform rash modified MESTT grading scale (facial assessment) at Week 8
• Time to first response of 1 grade improvement from Baseline on the acneiform rash modified MESTT grading scale (facial assessment)
• Change and percent change from Baseline in pruritus NRS at Week 8
• Change and percent change from Baseline in pain NRS at Week 8
• Change from Baseline in FACT-EGFRi-18 at Week 8
• Incidence of AEs, SAEs, and AEs leading to withdrawals, as well as changes in vital signs, clinical laboratory parameters (hematology, biochemistry, and urinalysis), and 12-lead ECGs |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| 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 | 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 |
| To test for immunogenicity to ANB019 |
|
| 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 | 2 |
| 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.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 17 |
| 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 | 4 |
| 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 | 5 |
Print
