Clinical trial NCT05905133: A Study to Evaluate the Safety and Efficacy of CBP-201 in Chinese Adult Subjects With Moderate to Severe AD
Official title: A Multi-Center, Single-Arm, Open-Label Clinical Study to Evaluate the Safety and Efficacy of CBP-201 in Chinese Adult Subjects With Moderate to Severe Atopic Dermatitis
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Atopic Dermatitis
Lead sponsor: Connect Biopharm LLC
Sponsor class: INDUSTRY
First posted: 2023-06-15
Enrollment: 360
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is a single-arm, open-label, multi-center clinical study designed to assess the safety and efficacy of CBP-201 in eligible subjects with moderate to severe Atopic Dermatitis.

Detailed description: The study includes a screening period, a treatment period and a follow-up period.

The subjects will receive a subcutaneous injection of CBP-201 600 mg (4 mL in total, 2 injections of 2 mL each in different sites) on Day1, begin to receive a subcutaneous injection of CBP-201 300 mg (2 mL) from Week2, and receive CBP-201 300 mg (2 mL) every 2 weeks thereafter until Week10.

Eligibility criteria: Inclusion Criteria:

1. 18 ≤ age ≤ 75 years at the screening visit, male or female.
2. Diagnosed with atopic dermatitis (according to the American Academy of Dermatology's Guidelines of care for the management of atopic dermatitis, 2014\[1\]) at the time of screening, and meeting all the 4 criteria below:

   1. Suffering from the disease for more than 1 year at the time of screening;
   2. At the screening and baseline visit, IGA score ≥ 3 (according to the validated Investigator Global Assessment for Atopic Dermatitis \[vIGA-AD™\] scale);
   3. EASI score ≥ 12;
   4. Percentage of total BSA affected by AD ≥ 10%.
3. Female subjects of childbearing potential (FCBP) and male subjects who have not undergone vasectomy must agree to take highly effective contraceptive measures during the entire study period (from the signing of informed consent forms (ICFs) to the 8-week follow-up period after discontinuation of study drug). Postmenopausal women (determined by testing follicle stimulating hormone \[FSH\]; defined as the women who have had amenorrhea for at least 12 consecutive months without using drugs known to cause amenorrhea, and have a recorded FSH level greater than 40 mIU/mL or in the postmenopausal range) and women with a record of surgical sterilization (i.e., tubal ligation or hysterectomy or bilateral oophorectomy) before the screening visit can be considered infertile.

   Highly effective contraceptive measures include:

   i. Abstinence (acceptable only if it is part of the subject's routine lifestyle); ii. Hormones (oral, patch, ring, injection, implant) combined with male condoms. This measure must be used at least 30 days before the first study drug administration. Otherwise, another acceptable method of contraception must be used; iii. Intrauterine device (IUD) combined with male condoms.
4. Subjects are willing and able to comply with study visits and related procedures.
5. Subjects have the ability to learn the study requirements and process, and voluntarily take part in the clinical trial and sign an ICF.

Exclusion Criteria:

1. Received prior treatment with anti-interleukin-4 receptor α (IL-4Rα)/anti-interleukin-13 (IL-13) antibodies with a poor response (including treatment failure or development of unacceptable treatment-related adverse reactions).
2. Have received any of the following topical treatments within 2 weeks before D1 visit: phosphodiesterase-4 (PDE-4) inhibitors, Janus kinase (JAK) inhibitors, or aromatic hydrocarbon receptor agonists.
3. Have received systemic treatment with corticosteroids (except for corticosteroid inhalers and nasal sprays) or other immunosuppressive/immunomodulatory agents (including but not limited to cyclosporine, mycophenolate mofetil, azathioprine, methotrexate, JAK inhibitors, and various biological agents) within 2 weeks before D1 visit or 5 drug half-lives (if known), whichever is longer.
4. Have received treatment with immune cell depletion agents (e.g., rituximab) within 6 months before D1 visit.
5. Have received any investigational drug/treatment within 4 weeks before D1 visit or 5 drug half-lives (if known), whichever is longer.
6. Other skin complications in addition to AD that may interfere with the study assessments.
7. There is a known or suspected history of immunosuppression/immunodeficiency within 6 months before D1 visit (including but not limited to a history of invasive opportunistic infections, such as aspergillosis, coccidiosis, histoplasmosis, acquired immunodeficiency syndrome (AIDS), listeriosis, or Pneumocystis, even if the infection has subsided), or there is an abnormally frequently recurrent or persistent infection.
8. Received systemic treatment with anti-infective drugs (including but not limited to antibiotics, antiviral drugs, antiparasitic drugs, antiprotozoal drugs, or antifungal drugs) due to acute or chronic infection within 1 week before D1 visit (after the infection subsides, the subjects can be rescreened).
9. History of malignant tumor within 5 years before D1 visit (except for completely cured cervical carcinoma in situ or non-metastatic cutaneous squamous cell carcinoma or basal cell carcinoma).
10. History of parasite infection within 6 months before D1 visit.
11. Positive for hepatitis B surface antigen (HBsAg), or positive for hepatitis B core antibody (HBcAb) and HBV-DNA, or positive for hepatitis C antibody and HCV ribonucleic acid (RNA) polymerase chain reaction, or serologically positive for human immunodeficiency virus (HIV) at the screening visit.
12. Subjects with active tuberculosis, latent tuberculosis, or a history of nontuberculous mycobacterial infection at screening;

    Note:
    * Unless there is a clear medical record proving that the subject has received adequate treatment and is currently able to start receiving biological treatment (based on the medical judgment of the investigator and/or infectious disease specialist);
    * If needed, an interferon gamma release assay may be used to assist diagnosis of suspected tuberculosis.
13. Any of the following laboratory test abnormalities at the screening visit:

    1. Aspartate aminotransferase or alanine aminotransferase \> 2 times the upper limit of normal (ULN);
    2. Total bilirubin \> 1.5 × ULN;
    3. Serum creatinine \> 1.2 × ULN;
    4. White blood cell count \< 3.0 × 109/L or ≥ 14 × 109/L; Note: If the subjects have the above laboratory test abnormalities at screening, after being assessed as necessary by the investigator, they are allowed to receive a retest on another day within 28 days of the screening period, and those qualified for the retest are permitted to be enrolled (it is forbidden to conduct drug intervention for those laboratory test abnormalities before retest).
14. History of hypersensitivity to L-histidine, trehalose or Tween (polysorbate) 80, or systemic hypersensitivity reactions to any biological agents (except local injection site reactions).
15. History of alcohol or drug abuse within 2 years before D1 visit.
16. Have been vaccinated with (attenuated) live vaccine within 8 weeks before D1 visit, or planning to be vaccinated during the study period.
17. Planning to undergo major surgical operations during the study period.
18. Pregnant or lactating women, or subjects with pregnancy or lactation plans during the study period.
19. Any other conditions (e.g., those may increase the risks of the subjects, or may affect/interfere with the assessment of the study) that the investigator deems unsuitable for participation in this study, including but not limited to: prior or current physical or mental illness, clinically significant physical examination results, vital signs, or safety laboratory test abnormalities at screening. The specific reasons for subjects excluded due to this criterion will be indicated in the study documents (including medical records and electronic case report form (eCRF)).

Primary outcomes:
measure: Incidence of treatment-emergent adverse events (TEAEs)
timeFrame: From Day 1 study drug first administrated to Week 20
Secondary outcomes:
measure: Incidence of treatment-related treatment-emergent adverse events (TEAEs)
timeFrame: From Day 1 study drug first administrated to Week 20
measure: Incidence of serious adverse events (SAEs)
timeFrame: From Day 1 study drug first administrated to Week 20
measure: Incidence of treatment-related serious adverse events (SAEs)
timeFrame: From Day 1 study drug first administrated to Week 20
measure: Incidence of adverse events of special interest (AESIs)
timeFrame: From Day 1 study drug first administrated to Week 20
measure: Abnormal changes in vital signs
timeFrame: Pre-dose, Day1, Day15, Day29, Day43, Day57, Day71, Day85, Day113, Day141
measure: Abnormal changes in physical examination
timeFrame: Pre-dose, Day85, Day141
measure: Abnormal changes in laboratory tests: Hematology
timeFrame: Pre-dose, Day1, Day15, Day29, Day57, Day85, Day141
measure: Abnormal changes in laboratory tests: Blood biochemistry
timeFrame: Pre-dose, Day1, Day15, Day29, Day57, Day85, Day141
measure: Abnormal changes in laboratory tests: Urinalysis
timeFrame: Pre-dose, Day1, Day15, Day29, Day57, Day85, Day141
measure: Abnormal changes in electrocardiogram (ECG) parameters
timeFrame: Pre-dose, Day1, Day141
measure: Proportion of subjects achieving greater than or equal to 75% improvement in Eczema Area and Severity Index (EASI-75)
timeFrame: Day1, Day15, Day29, Day57, Day85, Day113, Day141
measure: Proportion of subjects whose Investigator Global Assessment (IGA) score is 0-1 and decreased by ≥ 2 points from baseline
timeFrame: Day1, Day15, Day29, Day57, Day85, Day113, Day141
measure: Proportion of subjects achieving greater than or equal to 50% improvement in Eczema Area and Severity Index (EASI-50)
timeFrame: Day1, Day15, Day29, Day57, Day85, Day113, Day141
measure: Proportion of subjects achieving greater than or equal to 90% improvement in Eczema Area and Severity Index (EASI-90)
timeFrame: Day1, Day15, Day29, Day57, Day85, Day113, Day141
measure: Proportion of subjects achieving 100% improvement in Eczema Area and Severity Index (EASI-100)
timeFrame: Day1, Day15, Day29, Day57, Day85, Day113, Day141
measure: Proportion of subjects whose IGA score is decreased by ≥ 2 points from baseline
timeFrame: Day1, Day15, Day29, Day57, Day85, Day113, Day141
measure: Proportion of subjects with IGA score ≤ 2 (equivalent to reaching a low disease activity state)
timeFrame: Day1, Day15, Day29, Day57, Day85, Day113, Day141
measure: Proportion of subjects whose weekly average Peak Pruritus Numerical Rating Scale (PP-NRS) is decreased by ≥ 3 points from baseline
timeFrame: Day1, Day15, Day29, Day43, Day57, Day71, Day85, Day113, Day141
measure: Proportion of subjects whose weekly average Peak Pruritus Numerical Rating Scale (PP-NRS) is decreased by ≥ 4 points from baseline
timeFrame: Day1, Day15, Day29, Day43, Day57, Day71, Day85, Day113, Day141
measure: Change and percentage change in the EASI score from baseline
timeFrame: Day1, Day15, Day29, Day57, Day85, Day113, Day141
measure: Change and percentage change in the weekly average PP-NRS from baseline
timeFrame: Day1, Day15, Day29, Day43, Day57, Day71, Day85, Day113, Day141
measure: Change and percentage change in the body surface area (BSA) affected by Atopic Dermatitis from baseline
timeFrame: Day1, Day15, Day29, Day57, Day85, Day113, Day141
measure: Change and percentage change in the Dermatology Life Quality Index (DLQI) score from baseline
timeFrame: Day1, Day15, Day29, Day57, Day85, Day113, Day141
measure: Proportion of subjects receiving concomitant medications for the treatment of the disease under study (Atopic Dermatitis)
timeFrame: from Day1 to Week12
measure: Proportion of subjects receiving concomitant medications for the treatment of the disease under study (Atopic Dermatitis) prohibited by the protocol
timeFrame: from Day1 to Week12
measure: Proportion of subjects receiving topical corticosteroids (TCS) for the treatment of the disease under study (Atopic Dermatitis)
timeFrame: from Day1 to Week12
measure: Duration of TCS use for the treatment of the disease under study (Atopic Dermatitis)
timeFrame: from Day1 to Week12
measure: Percentage of subjects positive for anti-drug antibody (ADA) and ADA titer range
timeFrame: Day1, Day15, Day29, Day57, Day85, Day141
measure: Percentage of subjects positive for neutralizing antibody (NAb) in subjects positive for ADA
timeFrame: Day1, Day15, Day29, Day57, Day85, Day141
Other outcomes:
Locations:
city: Beijing
country: China
facility: Connect Investigative Site 01
state: Beijing
city: Beijing
country: China
facility: Connect Investigative Site 41
state: Beijing
city: Fuzhou
country: China
facility: Connect Investigative Site 14
state: Fujian
city: Fuzhou
country: China
facility: Connect Investigative Site 25
state: Fujian
city: Guangzhou
country: China
facility: Connect Investigative Site 03
state: Guangdong
city: Guangzhou
country: China
facility: Connect Investigative Site 11
state: Guangdong
city: Guangzhou
country: China
facility: Connect Investigative Site 13
state: Guangdong
city: Guangzhou
country: China
facility: Connect Investigative Site 20
state: Guangdong
city: Shenzhen
country: China
facility: Connect Investigative Site 22
state: Guangdong
city: Nanning
country: China
facility: Connect Investigative Site 31
state: Guangxi
city: Haikou
country: China
facility: Connect Investigative Site 16
state: Hainan
city: Haikou
country: China
facility: Connect Investigative Site 17
state: Hainan
city: Nanyang
country: China
facility: Connect Investigative Site 19
state: Henan
city: Wuhan
country: China
facility: Connect Investigative Site 27
state: Hubei
city: Yichang
country: China
facility: Connect Investigative Site 28
state: Hubei
city: Changsha
country: China
facility: Connect Investigative Site 26
state: Hunan
city: Nanjing
country: China
facility: Connect Investigative Site 34
state: Jiangsu
city: Suzhou
country: China
facility: Connect Investigative Site 39
state: Jiangsu
city: Zhenjiang
country: China
facility: Connect Investigative Site 05
state: Jiangsu
city: Shenyang
country: China
facility: Connect Investigative Site 29
state: Liaoning
city: Jiangxi
country: China
facility: Connect Investigative Site 40
state: Nanchang
city: Baotou
country: China
facility: Connect Investigative Site 24
state: Nei Monggol
city: Yinchuan
country: China
facility: Connect Investigative Site 18
state: Ningxia
city: Dongying
country: China
facility: Connect Investigative Site 30
state: Shandong
city: Jinan
country: China
facility: Connect Investigative Site 21
state: Shandong
city: Jinan
country: China
facility: Connect Investigative Site 35
state: Shandong
city: Shanghai
country: China
facility: Connect Investigative Site 36
state: Shanghai
city: Taiyuan
country: China
facility: Connect Investigative Site 10
state: Shanxi
city: Xi'an
country: China
facility: Connect Investigative Site 06
state: Shanxi
city: Yuncheng
country: China
facility: Connect Investigative Site 15
state: Shanxi
city: Chengdu
country: China
facility: Connect Investigative Site 23
state: Sichuan
city: Tianjin
country: China
facility: Connect Investigative Site 02
state: Tianjin
city: Ürümqi
country: China
facility: Connect Investigative Site 09
state: Xinjiang
city: Hangzhou
country: China
facility: Connect Investigative Site 07
state: Zhejiang
city: Hangzhou
country: China
facility: Connect Investigative Site 08
state: Zhejiang
city: Hangzhou
country: China
facility: Connect Investigative Site 33
state: Zhejiang
city: Hangzhou
country: China
facility: Connect Investigative Site 37
state: Zhejiang
city: Ningbo
country: China
facility: Connect Investigative Site 32
state: Zhejiang
Study officials:
affiliation: Connect Biopharm LLC
name: Suzhou Connect
role: STUDY_DIRECTOR
References: