A Study to Evaluate the Safety and Efficacy of CBP-201 in Chinese Adult Subjects With Moderate to Severe AD

Atopic Dermatitis Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05905133
• Other study ID #: CBP-201-CN003
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: July 15, 2023
• Est. completion date: June 30, 2024

Study information

• Verified date: December 2023
• Source: Suzhou Connect Biopharmaceuticals, Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 360
• Est. completion date: June 30, 2024
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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 a (IL-4Ra)/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)).

Related Conditions & MeSH terms

• Atopic Dermatitis
• Dermatitis
• Dermatitis, Atopic
• Eczema

Intervention

Drug:
• CBP-201
subcutaneous injection

Locations

Country	Name	City	State
China	Connect Investigative Site 24	Baotou	Nei Monggol
China	Connect Investigative Site 01	Beijing	Beijing
China	Connect Investigative Site 41	Beijing	Beijing
China	Connect Investigative Site 26	Changsha	Hunan
China	Connect Investigative Site 23	Chengdu	Sichuan
China	Connect Investigative Site 30	Dongying	Shandong
China	Connect Investigative Site 14	Fuzhou	Fujian
China	Connect Investigative Site 25	Fuzhou	Fujian
China	Connect Investigative Site 03	Guangzhou	Guangdong
China	Connect Investigative Site 11	Guangzhou	Guangdong
China	Connect Investigative Site 13	Guangzhou	Guangdong
China	Connect Investigative Site 20	Guangzhou	Guangdong
China	Connect Investigative Site 16	Haikou	Hainan
China	Connect Investigative Site 17	Haikou	Hainan
China	Connect Investigative Site 07	Hangzhou	Zhejiang
China	Connect Investigative Site 08	Hangzhou	Zhejiang
China	Connect Investigative Site 33	Hangzhou	Zhejiang
China	Connect Investigative Site 37	Hangzhou	Zhejiang
China	Connect Investigative Site 40	Jiangxi	Nanchang
China	Connect Investigative Site 21	Jinan	Shandong
China	Connect Investigative Site 35	Jinan	Shandong
China	Connect Investigative Site 34	Nanjing	Jiangsu
China	Connect Investigative Site 31	Nanning	Guangxi
China	Connect Investigative Site 19	Nanyang	Henan
China	Connect Investigative Site 32	Ningbo	Zhejiang
China	Connect Investigative Site 36	Shanghai	Shanghai
China	Connect Investigative Site 29	Shenyang	Liaoning
China	Connect Investigative Site 22	Shenzhen	Guangdong
China	Connect Investigative Site 39	Suzhou	Jiangsu
China	Connect Investigative Site 10	Taiyuan	Shanxi
China	Connect Investigative Site 02	Tianjin	Tianjin
China	Connect Investigative Site 09	Ürümqi	Xinjiang
China	Connect Investigative Site 27	Wuhan	Hubei
China	Connect Investigative Site 06	Xi'an	Shanxi
China	Connect Investigative Site 28	Yichang	Hubei
China	Connect Investigative Site 18	Yinchuan	Ningxia
China	Connect Investigative Site 15	Yuncheng	Shanxi
China	Connect Investigative Site 05	Zhenjiang	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
Suzhou Connect Biopharmaceuticals, Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of treatment-emergent adverse events (TEAEs)	cases/person-years	From Day 1 study drug first administrated to Week 20
Secondary	Incidence of treatment-related treatment-emergent adverse events (TEAEs)	cases/person-years	From Day 1 study drug first administrated to Week 20
Secondary	Incidence of serious adverse events (SAEs)	cases/person-years	From Day 1 study drug first administrated to Week 20
Secondary	Incidence of treatment-related serious adverse events (SAEs)	cases/person-years	From Day 1 study drug first administrated to Week 20
Secondary	Incidence of adverse events of special interest (AESIs)	cases/person-years	From Day 1 study drug first administrated to Week 20
Secondary	Abnormal changes in vital signs	Vital signs (VS): including body temperature, respiration rate, blood pressure, and heart rate.	Pre-dose, Day1, Day15, Day29, Day43, Day57, Day71, Day85, Day113, Day141
Secondary	Abnormal changes in physical examination	Physical examination included are as follows: general appearance, skin, ears/nose/throat, head and neck, cardiovascular system, respiratory system, abdomen, limbs, lymph nodes, musculoskeletal and nervous systems.	Pre-dose, Day85, Day141
Secondary	Abnormal changes in laboratory tests: Hematology	White blood cell count, Hemoglobin, Hematocrit, Red blood cell count, Platelet count, Neutrophil percentage, Lymphocyte percentage, Monocyte percentage, Basophil percentage, Eosinophil percentage, Absolute neutrophil count, Absolute lymphocyte count, Absolute monocyte count, Absolute eosinophil count, Absolute basophil count	Pre-dose, Day1, Day15, Day29, Day57, Day85, Day141
Secondary	Abnormal changes in laboratory tests: Blood biochemistry	Sodium, Potassium, Calcium, Chlorine, Serum urea/urea nitrogen, Creatinine, Glucose, Total protein, Albumin, Total bilirubin, Alanine aminotransaminase, Aspartate aminotransferase, ?-glutamyltransferase, Alkaline phosphatase, Lactate dehydrogenase, Creatine phosphokinase, Total cholesterol, Low-density lipoprotein, High-density lipoprotein	Pre-dose, Day1, Day15, Day29, Day57, Day85, Day141
Secondary	Abnormal changes in laboratory tests: Urinalysis	Urine bilirubin, Urine red blood cells, Urine white blood cells, Urine glucose, Urine ketone, Urine nitrite, Urine pH, Urine protein, Urine specific gravity, Urobilinogen, Microscopic examination (if necessary)	Pre-dose, Day1, Day15, Day29, Day57, Day85, Day141
Secondary	Abnormal changes in electrocardiogram (ECG) parameters	ECG variables include ventricular heart rate and PR, QRS, QT, and QTcF intervals.	Pre-dose, Day1, Day141
Secondary	Proportion of subjects achieving greater than or equal to 75% improvement in Eczema Area and Severity Index (EASI-75)	The Eczema Area and Severity Index (EASI) scale quantifies the severity and extent of Atopic Dermatitis, as well as the severity of erythema, infiltration, excoriation, and lichenification of the four anatomical regions-head and neck, trunk, upper extremities, and lower extremities.	Day1, Day15, Day29, Day57, Day85, Day113, Day141
Secondary	Proportion of subjects whose Investigator Global Assessment (IGA) score is 0-1 and decreased by = 2 points from baseline	The Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD™) Scale is a 5-point classification scale based on the overall appearance of the skin lesions at a specific time point.	Day1, Day15, Day29, Day57, Day85, Day113, Day141
Secondary	Proportion of subjects achieving greater than or equal to 50% improvement in Eczema Area and Severity Index (EASI-50)	The Eczema Area and Severity Index (EASI) scale quantifies the severity and extent of Atopic Dermatitis, as well as the severity of erythema, infiltration, excoriation, and lichenification of the four anatomical regions-head and neck, trunk, upper extremities, and lower extremities.	Day1, Day15, Day29, Day57, Day85, Day113, Day141
Secondary	Proportion of subjects achieving greater than or equal to 90% improvement in Eczema Area and Severity Index (EASI-90)	The Eczema Area and Severity Index (EASI) scale quantifies the severity and extent of Atopic Dermatitis, as well as the severity of erythema, infiltration, excoriation, and lichenification of the four anatomical regions-head and neck, trunk, upper extremities, and lower extremities.	Day1, Day15, Day29, Day57, Day85, Day113, Day141
Secondary	Proportion of subjects achieving 100% improvement in Eczema Area and Severity Index (EASI-100)	The Eczema Area and Severity Index (EASI) scale quantifies the severity and extent of Atopic Dermatitis, as well as the severity of erythema, infiltration, excoriation, and lichenification of the four anatomical regions-head and neck, trunk, upper extremities, and lower extremities.	Day1, Day15, Day29, Day57, Day85, Day113, Day141
Secondary	Proportion of subjects whose IGA score is decreased by = 2 points from baseline	The Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD™) Scale is a 5-point classification scale based on the overall appearance of the skin lesions at a specific time point.	Day1, Day15, Day29, Day57, Day85, Day113, Day141
Secondary	Proportion of subjects with IGA score = 2 (equivalent to reaching a low disease activity state)	The Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD™) Scale is a 5-point classification scale based on the overall appearance of the skin lesions at a specific time point.	Day1, Day15, Day29, Day57, Day85, Day113, Day141
Secondary	Proportion of subjects whose weekly average Peak Pruritus Numerical Rating Scale (PP-NRS) is decreased by = 3 points from baseline	Peak Pruritus Numerical Rating Scale (PP-NRS) is a single self-reported item designed to measure the peak pruritus or the "worst" pruritus in the previous 24 hours.	Day1, Day15, Day29, Day43, Day57, Day71, Day85, Day113, Day141
Secondary	Proportion of subjects whose weekly average Peak Pruritus Numerical Rating Scale (PP-NRS) is decreased by = 4 points from baseline	Peak Pruritus Numerical Rating Scale (PP-NRS) is a single self-reported item designed to measure the peak pruritus or the "worst" pruritus in the previous 24 hours.	Day1, Day15, Day29, Day43, Day57, Day71, Day85, Day113, Day141
Secondary	Change and percentage change in the EASI score from baseline	The Eczema Area and Severity Index (EASI) scale quantifies the severity and extent of Atopic Dermatitis, as well as the severity of erythema, infiltration, excoriation, and lichenification of the four anatomical regions-head and neck, trunk, upper extremities, and lower extremities.	Day1, Day15, Day29, Day57, Day85, Day113, Day141
Secondary	Change and percentage change in the weekly average PP-NRS from baseline	Peak Pruritus Numerical Rating Scale (PP-NRS) is a single self-reported item designed to measure the peak pruritus or the "worst" pruritus in the previous 24 hours.	Day1, Day15, Day29, Day43, Day57, Day71, Day85, Day113, Day141
Secondary	Change and percentage change in the body surface area (BSA) affected by Atopic Dermatitis from baseline	The "Rule of Nines" is used to estimate the maximum percentage of Atopic Dermatitis-affected body surface area (BSA): head and neck [9%], anterior trunk [18%], back [18%], upper limbs [18%], lower limbs [36%], and genitals [1%].	Day1, Day15, Day29, Day57, Day85, Day113, Day141
Secondary	Change and percentage change in the Dermatology Life Quality Index (DLQI) score from baseline	Dermatology Life Quality Index (DLQI) is a questionnaire containing 10 items to assess the impact of Atopic Dermatitis on quality of life (QOL) in the past week, and the scores range from 0 (no disease) to 30 (severe disease); the higher the score, the worse the quality of life.	Day1, Day15, Day29, Day57, Day85, Day113, Day141
Secondary	Proportion of subjects receiving concomitant medications for the treatment of the disease under study (Atopic Dermatitis)	except emollients; the proportion will be summarized separately by all concomitant medications and the ATC2 codes for concomitant medications	from Day1 to Week12
Secondary	Proportion of subjects receiving concomitant medications for the treatment of the disease under study (Atopic Dermatitis) prohibited by the protocol	(except emollients; the proportion will be summarized separately by all concomitant medications, local therapy, systemic treatment, and the ATC2 codes for concomitant medications)	from Day1 to Week12
Secondary	Proportion of subjects receiving topical corticosteroids (TCS) for the treatment of the disease under study (Atopic Dermatitis)	If topical corticosteroids (TCS) is considered necessary by the investigator.	from Day1 to Week12
Secondary	Duration of TCS use for the treatment of the disease under study (Atopic Dermatitis)	days/person-years	from Day1 to Week12
Secondary	Percentage of subjects positive for anti-drug antibody (ADA) and ADA titer range	Descriptive statistics will be used to summarize the baseline values of related measurements (ADA, NAb) and the changes from baseline to each visit.	Day1, Day15, Day29, Day57, Day85, Day141
Secondary	Percentage of subjects positive for neutralizing antibody (NAb) in subjects positive for ADA	Descriptive statistics will be used to summarize the baseline values of related measurements (ADA, NAb) and the changes from baseline to each visit.	Day1, Day15, Day29, Day57, Day85, Day141