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This study will evaluate the efficacy, safety, pharmacokinetics and pharmacodynamics of CBP-201 in adult subjects with moderate to severe atopic dermatitis.
This is a randomized, double-blind, placebo-controlled, dose regimen finding study to assess the efficacy, safety, and steady-state PK profile of CBP-201 administered to eligible adult subjects with moderate to severe atopic dermatitis compared to placebo. CBP-201 is administered as a subcutaneous (SC) injection. The study is divided into a treatment period of 16 weeks and a follow-up period of 8 weeks.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| CBP-201 Dose 1 | Experimental | CBP-201 Dose 1 subcutaneous (SC) injection |
|
| CBP-201 Dose 2 | Experimental | CBP-201 Dose 2 subcutaneous (SC) injection |
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| CBP-201 Dose 3 | Experimental | CBP-201 Dose 3 subcutaneous (SC) injection |
|
| placebo | Placebo Comparator | subcutaneous (SC) injection |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CBP-201 | Drug | CBP-201 subcutaneous(SC) injection. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percent Reduction in EASI Score From Baseline to Week 16 | EASI=Eczema Area Severity Index is a validated physician score for signs of atopic dermatitis. EASI can range from 0 to 72. An EASI score of 0 indicates clear/no eczema, 0.1 to 1.0 almost clear, 1.1 to 7 mild disease, 7.1 to 21 moderate disease, 21.1 to 50 severe disease, and 51-72 indicates very severe disease. EASI Sub-scale ranges are as follows: Head/neck can range from 0-7.2, Trunk 0-14.4, Upper Extremities 0-21.6, Lower Extremities can range from 0-28.8. To calculate EASI, % involvement is first assessed by body region with an Area involvement Score of 0-6 for each region: 0=0%, 1=1-9%, 2=10-29%, 3=30-39%, 4=50-69%, 5=70-89%, 6=90-100% involvement. Then 4 attributes (Erythema, Edema/Papulation, Excoriation, and Lichenification) are scored for severity (0= none, 1=mild, 2=moderate, 3=severe). A multiplier is applied head/neck=0.1, trunk=0.2, upper extremities= 0.3, lower extremities=0.4. The total EASI score is the sum of 4 regional sub-scores. | Reduction from baseline to 16 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| vIGA of 0/1 at Week 16 | Validated Investigator Global Assessment Score (vIGA) is assigned by the physician based on morphologic presentation of the disease in the clinic. The physician considers extent and severity of erythema, induration/papulation, lichenification, and oozing/crusting. A vIGA Score of 0=Clear, 1=Almost Clear, 2= Mild dermatitis, 3=Moderate dermatitis, and 4= Severe dermatitis. Patients are required to have a baseline IGA of 3 or 4. The response rate or percentage of patients achieving a vIGA of 0 or 1 (improved to clear or almost clear) at week 16 is the outcome. |
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Inclusion Criteria:
Exclusion Criteria:
Have any of the following laboratory abnormalities at Screening:
Have undergone treatment with any of the following:
Have any of the following:
Women must not be pregnant, planning to become pregnant or breast-feed during the study
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| Name | Affiliation | Role |
|---|---|---|
| Suzhou Connect | Connect Biopharm LLC | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Connect Investigative Site 310 | Glendale | Arizona | 85308 | United States | ||
| Connect Investigative Site 338 |
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After providing informed consent, patients were assessed for study eligibility within 45 days before the baseline visit. Of the 394 patients screeened, 226 patients met the eligibility criteria and were randomized to treatment.
Patients were recruited based on physician referrral at academic and non-academic clinical centers between Jun 2020 and Sep 2021; 394 patients were screened. The first participant was randomized to treatment on 30 Jun 2020 and the last patient was randomized in April 2021. The last patient last visit was 22 Sept 2021.
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| ID | Title | Description |
|---|---|---|
| FG000 | CBP-201 150 Q2W | CBP-201 1800 mg, 600 mg Loading dose followed by 150 mg Q2W for 16 weeks |
| FG001 | CBP-201 300 Q2W | CBP-201 3000 mg, 600 mg Loading dose followed by 300 mg Q2W for 16 weeks |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | May 28, 2020 | Sep 13, 2022 |
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| placebo | Drug | subcutaneous(SC) injection |
|
| Response Rate at 16 weeks |
| Phoenix |
| Arizona |
| 85001 |
| United States |
| Connect Investigative Site 316 | Tempe | Arizona | 85284 | United States |
| Connect Investigative Site 305 | Little Rock | Arkansas | 72204 | United States |
| Connect Investigative Site 327 | Canoga Park | California | 91303 | United States |
| Connect Investigative Site 324 | Encinitas | California | 92024 | United States |
| Connect Investigative Site 301 | Fremont | California | 94538 | United States |
| Connect Investigative Site 312 | Huntington Beach | California | 92647 | United States |
| Connect Investigative Site 329 | Mission Viejo | California | 92691 | United States |
| Connect Investigative Site 322 | San Diego | California | 92123 | United States |
| Connect Investigative Site 323 | San Luis Obispo | California | 93405 | United States |
| Connect Investigative Site 317 | Santa Ana | California | 92703 | United States |
| Connect Investigative Site 318 | Sherman Oaks | California | 91403 | United States |
| Connect Investigative Site 325 | Thousand Oaks | California | 91320 | United States |
| Connect Investigative Site 332 | Coral Gables | Florida | 33144 | United States |
| Connect Investigative Site 320 | Hialeah | Florida | 33016 | United States |
| Connect Investigative Site 306 | Hollywood | Florida | 33021 | United States |
| Connect Investigative Site 308 | Jacksonville | Florida | 32256 | United States |
| Connect Investigative Site 314 | Maitland | Florida | 32751 | United States |
| Connect Investigative Site 331 | Miami | Florida | 33155 | United States |
| Connect Investigative Site 337 | Miami | Florida | 33155 | United States |
| Connect Investigative Site 321 | Miami | Florida | 33173 | United States |
| Connect Investigative Site 304 | Orlando | Florida | 32801 | United States |
| Connect Investigative Site 340 | Weston | Florida | 33331 | United States |
| Connect Investigative Site 333 | Chicago | Illinois | 60640 | United States |
| Connect Investigative Site 303 | Chicago | Illinois | 60660 | United States |
| Connect Investigative Site 307 | New Albany | Indiana | 47150 | United States |
| Connect Investigative Site 313 | West Lafayette | Indiana | 47906 | United States |
| Connect Investigative Site 311 | Louisville | Kentucky | 40241 | United States |
| Connect Investigative Site 319 | Hunt Valley | Maryland | 21030 | United States |
| Connect Investigative Site 335 | Saint Joseph | Missouri | 64506 | United States |
| Connect Investigative Site 315 | St Louis | Missouri | 63110 | United States |
| Connect Investigative Site 336 | Las Vegas | Nevada | 89109 | United States |
| Connect Investigative Site 326 | Albuquerque | New Mexico | 87102 | United States |
| Connect Investigative Site 330 | Cincinnati | Ohio | 45231 | United States |
| Connect Investigative Site 328 | Rapid City | South Dakota | 57702 | United States |
| Connect Investigative Site 309 | Memphis | Tennessee | 38119 | United States |
| Connect Investigative Site 334 | Houston | Texas | 77065 | United States |
| Connect Investigative Site 111 | Canberra | Australian Capital Territory | 2606 | Australia |
| Connect Investigative Site 104 | Darlinghurst | New South Wales | 2010 | Australia |
| Connect Investigative Site 108 | Kanwal | New South Wales | 2259 | Australia |
| Connect Investigative Site 105 | Sydney | New South Wales | 2289 | Australia |
| Connect Investigative Site 101 | Brisbane | Queensland | 4102 | Australia |
| Connect Investigative Site 102 | Melbourne | Victoria | 3002 | Australia |
| Connect Investigative Site 106 | Fremantle | Western Australia | 6160 | Australia |
| Connect Investigative Site 103 | Perth | Western Australia | 6009 | Australia |
| Connect Investigative Site 408 | Beijing | Beijing Municipality | 100020 | China |
| Connect Investigative Site 404 | Beijing | Beijing Municipality | 100050 | China |
| Connect Investigative Site 405 | Wuxi | Jiangsu | 214002 | China |
| Connect Investigative Site 409 | Zhenjiang | Jiangsu | 212001 | China |
| Connect Investigative Site 402 | Jinan | Shandong | 250013 | China |
| Connect Investigative Site 401 | Shanghai | Shanghai Municipality | 200040 | China |
| Connect Investigative Site 406 | Shanghai | Shanghai Municipality | 200071 | China |
| Connect Investigative Site 410 | Tianjin | Tianjin Municipality | 300120 | China |
| Connect Investigative Site 403 | Hangzhou | Zhejiang | 310003 | China |
| Connect Investigative Site 204 | Tauranga | Bay of Plenty | 3110 | New Zealand |
| Connect Investigative Site 202 | Havelock North | Hawke's Bay Region | 4130 | New Zealand |
| Connect Investigative Site 205 | Waikanae | Kapiti Coast | 5036 | New Zealand |
| Connect Investigative Site 203 | Auckland | 1010 | New Zealand |
| FG002 | CBP-201 300 Q4W | CBP-201 1800 mg, 600 mg Loading dose followed by 300 mg Q4W for 16 weeks alternating with 2 mLs matched volume placebo Q4W for 16 weeks |
| FG003 | Placebo | Placebo, 4 mLs matched loading dose volume follwed by 2 mls matched volume Q2W for 16 weeks |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | CBP-201 150 Q2W | CBP-201 1800 mg, 600 mg Loading dose followed by 150 mg Q2W for 16 weeks |
| BG001 | CBP-201 300 Q2W | CBP-201 3000 mg, 600 mg Loading dose followed by 300 mg Q2W for 16 weeks |
| BG002 | CBP-201 300 Q4W | CBP-201 1800 mg, 600 mg Loading dose followed by 300 mg Q4W for 16 weeks alternating with 2 mLs matched volume placebo Q4W for 16 weeks |
| BG003 | Placebo | Placebo, 4 mLs matched loading dose volume follwed by 2 mls matched volume Q2W for 16 weeks |
| BG004 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Number | participants |
| ||||||||||||||||
| EASI Score | Eczema Area Severity Index Score | Mean | Standard Deviation | units on a scale |
| ||||||||||||||
| IGA Score | Count of Participants | Participants |
| ||||||||||||||||
| BSA | Body Surface Area affected by AD in % | Mean | Standard Deviation | percentage |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percent Reduction in EASI Score From Baseline to Week 16 | EASI=Eczema Area Severity Index is a validated physician score for signs of atopic dermatitis. EASI can range from 0 to 72. An EASI score of 0 indicates clear/no eczema, 0.1 to 1.0 almost clear, 1.1 to 7 mild disease, 7.1 to 21 moderate disease, 21.1 to 50 severe disease, and 51-72 indicates very severe disease. EASI Sub-scale ranges are as follows: Head/neck can range from 0-7.2, Trunk 0-14.4, Upper Extremities 0-21.6, Lower Extremities can range from 0-28.8. To calculate EASI, % involvement is first assessed by body region with an Area involvement Score of 0-6 for each region: 0=0%, 1=1-9%, 2=10-29%, 3=30-39%, 4=50-69%, 5=70-89%, 6=90-100% involvement. Then 4 attributes (Erythema, Edema/Papulation, Excoriation, and Lichenification) are scored for severity (0= none, 1=mild, 2=moderate, 3=severe). A multiplier is applied head/neck=0.1, trunk=0.2, upper extremities= 0.3, lower extremities=0.4. The total EASI score is the sum of 4 regional sub-scores. | All efficacy analyses were carried out using the FAS (all randomized subjects who received at least part of an SC dose of study drug based on planned treatment assignment (ie, "as randomized"). | Posted | Least Squares Mean | Standard Error | percent reduction from Baseline | Reduction from baseline to 16 weeks |
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| Secondary | vIGA of 0/1 at Week 16 | Validated Investigator Global Assessment Score (vIGA) is assigned by the physician based on morphologic presentation of the disease in the clinic. The physician considers extent and severity of erythema, induration/papulation, lichenification, and oozing/crusting. A vIGA Score of 0=Clear, 1=Almost Clear, 2= Mild dermatitis, 3=Moderate dermatitis, and 4= Severe dermatitis. Patients are required to have a baseline IGA of 3 or 4. The response rate or percentage of patients achieving a vIGA of 0 or 1 (improved to clear or almost clear) at week 16 is the outcome. | All efficacy analyses were carried out using the FAS (all randomized subjects who received at least part of an SC dose of study drug), based on planned treatment assignment (ie, "as randomized"). | Posted | Count of Participants | Participants | Response Rate at 16 weeks |
|
Adverse events were reported from the time the subject signed the informed consent and continued through the scheduled last visit (32 weeks after baseline visit), or if unresolved, until clinical recovery was complete.
An adverse event (AE) is any untoward medical occurrence in a subject administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. All AEs will be reported along with causality (related or not related) and Severity (CTCAE grading 1-5). In addition, AEs will be considered AEs of Special Interest (AESI) if they are involve ophthalmic complications (conjunctivitis or keratitis). Serious AEs will be reported within 24 hours to the Sponsor and CRO.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | CBP-201 150 Q2W | CBP-201 1800 mg, 600 mg Loading dose followed by 150 mg Q2W for 16 weeks | 0 | 57 | 1 | 57 | 26 | 57 |
| EG001 | CBP-201 300 Q2W | CBP-201 3000 mg, 600 mg Loading dose followed by 300 mg Q2W for 16 weeks | 0 | 57 | 0 | 57 | 21 | 57 |
| EG002 | CBP-201 300 Q4W | CBP-201 1800 mg, 600 mg Loading dose followed by 300 mg Q4W for 16 weeks alternating with 2 mLs matched volume placebo Q4W for 16 weeks | 1 | 56 | 2 | 56 | 34 | 56 |
| EG003 | Placebo | Placebo, 4 mLs matched loading dose volume follwed by 2 mls matched volume Q2W for 16 weeks | 0 | 56 | 2 | 56 | 31 | 56 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cholelithiasis | Hepatobiliary disorders | MedDRA 24.0 | Systematic Assessment |
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| Pneumonia | Infections and infestations | MedDRA 24.0 | Systematic Assessment |
| |
| Angina pectoris | Cardiac disorders | MedDRA 24.0 | Systematic Assessment |
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| Cardiac arrest | Cardiac disorders | MedDRA 24.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 24.0 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 24.0 | Systematic Assessment |
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| Rib fracture | Injury, poisoning and procedural complications | MedDRA 24.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 24.0 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dermatitis atopic | Skin and subcutaneous tissue disorders | MedDRA 24.0 | Systematic Assessment |
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| COVID-19 | Skin and subcutaneous tissue disorders | MedDRA 24.0 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 24.0 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA 24.0 | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA 24.0 | Systematic Assessment |
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| Conjunctivitis | Infections and infestations | MedDRA 24.0 | Systematic Assessment |
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| Skin infection | Infections and infestations | MedDRA 24.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 24.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 24.0 | Systematic Assessment |
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| Vision blurred | Eye disorders | MedDRA 24.0 | Systematic Assessment |
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| Eye pruritis | Eye disorders | MedDRA 24.0 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA 24.0 | Systematic Assessment |
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| Injection site reaction | General disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Pruritis | Skin and subcutaneous tissue disorders | MedDRA 24.0 | Systematic Assessment |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Malinda Longphre | Head of Clinical Operations US | +15105203361 | Mlongphre@connectpharm.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Oct 15, 2021 | Sep 20, 2022 | SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | Aug 7, 2020 | Sep 13, 2022 | ICF_002.pdf |
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| Between 18 and 65 years |
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| >=65 years |
|
| Male |
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| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
|
| Unknown or Not Reported |
|
| United States |
|
| China |
|
| Australia |
|
| IGA 4 = Severe disease |
|
| Superiority |
Pairwise comparisons for each CBP-201 group vs placebo were performed and a serial gate-keeping procedure was used for multiplicity adjustment. Each CBP-201 group was compared to placebo group in order from highest dose (300 mg Q2W) to the lowest dose frequency (300 mg Q4W), until statistical signficance at p=0.05 level was not achieved. |
| The sample size of the study was determined based on power calculations for the primary endpoint in patients receiving CBP-201 300 mg Q2W. Null hypothesis: CBP-201 150 Q2W is not superior to placebo in terms of percent reduction in EASI Score from Baseline to Week 16. | ANCOVA | The data were analyzed using an ANCOVA model with terms for treatment, baseline vIGA (moderate, severe), and baseline EASI. | 0.0067 | Adjusted for multiplicity using a serial gatekeeping procedure at the 5% in descending order: 1. 300 mg dose Q2W 2. 150 mg Q2W 3. 300 mg Q4W vs placebo. | Mean Difference (Final Values) | 17.89 | Standard Error of the Mean | 6.537 | 2-Sided | Superiority | Pairwise comparisons for each CBP-201 group vs placebo were performed and a serial gatekeeping procedure was used for multiplicity adjustment. Each CBP-201 group was compared with the placebo group in order from the highest dose (300 mg Q2W) to the lowest dose frequency (300 mg Q4W), until statistical significance at 0.05 level was not achieved. |
| The efficacy analysis includes comparing percentage reduction in EASI from baseline to Week 16 for CBP-201 300 mg Q4W regimen vs placebo. The sample size of the study was determined based on power calculations for the primary endpoint in patients receiving CBP-201 300 mg Q2W. Null hypothesis: CBP-201 300 Q4W is not superior to placebo in terms of percent reduction in EASI Score from Baseline to Week 16. | ANCOVA | The data were anlayzed using an ANCOVA model with terms for treatment, baseline vIGA (moderate, severe), and baseline EASI | 0.0004 | Adjusted for mulitplicity using a serial gatekeeping procedure at the 5% in descending order: 1. 300 mg dose Q2W 2. 150 mg Q2W 3. 300 mg Q4W vs placebo. | Mean Difference (Final Values) | 23.83 | Standard Error of the Mean | 6.575 | 2-Sided | Superiority | Pairwise comparisons for each CBP-201 group vs placebo were performed and a serial gatekeeping procedure was used for multiplicity adjustment. Each CBP-201 group was compared with placebo in order from highest dose (300 mg Q2W) to the lowest dose frequency (300 mg Q4W), until statistical significance at the 0.05 level was not achieved. |
| OG003 | Placebo | Placebo, 4 mLs matched loading dose volume follwed by 2 mls matched volume Q2W for 16 weeks |
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