A Single Ascending Dose Study in Healthy Participants and Multiple Ascending Dose Study of CNTO 7160 in Participants With Asthma and Participants With Atopic Dermatitis

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and tolerability of single ascending dose of CNTO 7160 administered intravenously (IV) in healthy participants and multiple dose administered IV in participants with asthma and atopic dermatitis.

Detailed Description
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This is a Phase 1, randomized, placebo-controlled, multicenter study of CNTO 7160. The study consists of Screening Period, In-patient period (6 days for healthy participants, 11 days for asthmatic participants and atopic dermatitis participants) and outpatient period (105 days for healthy participants, 110 days for asthmatic and atopic dermatitis participants). The total duration of participation for each participant will be approximately 21 weeks for healthy participants, 25 weeks for asthmatic participants, and atopic dermatitis participants. All eligible participants will be randomly assigned to receive active agent or placebo. The study will be conducted in 2 parts. In Part 1, single ascending doses of CNTO 7160 or placebo will be administered to sequential cohorts of healthy participants as an IV infusion. In Part 2, ascending multiple doses of CNTO 7160 or placebo will be administered as IV infusions to sequential cohorts of participants with asthma or atopic dermatitis. Blood samples will be collected for assessment of pharmacokinetic and pharmacodynamics parameters in both part 1 and 2 parameters, along with assessment of safety and clinical effects in part 2. Participants' safety will be monitored throughout the study.

Official Title
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A Phase 1, Randomized, Double-blind, Placebo-controlled, Single Ascending Dose Study in Healthy Subjects and Multiple Ascending Dose Study of CNTO 7160 in Subjects With Asthma and Subjects With Atopic Dermatitis

Conditions
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Asthma, Atopic Dermatitis, Healthy

Intervention / Treatment
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* Drug: Part 1: CNTO 7160
* Drug: Part 2 (Asthma): CNTO 7160
* Drug: Part 2 (Atopic Dermatitis): CNTO 7160
* Drug: Part 1 and Part 2: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Part 1 (Healthy Participants): Participant must have a body weight in the range of 50 to 100 kilogram (kg) inclusive and have a body mass index (BMI) of 19 to 30 kilogram per meter square (kg/m^2) inclusive Part 1 (Healthy Participants): Participant must be healthy on the basis of physical examination, medical history, vital signs and 12-lead ECG performed at screening Part 2 (Asthma Participants): Participant must have a body weight in the range of 50 to 125 kg inclusive and have a BMI of 19 to 32 kg/m^2 inclusive Part 2 (Asthma Participants): Participant must have a physician documented diagnosis of asthma for at least 12 months before screening Part 2 (Atopic Dermatitis Participants): Participant must have a body weight in the range of 50 to 100 kg inclusive and have a BMI of 19 to 30 kg/m^2 inclusive Part 2 (Atopic Dermatitis Participants): Participant has physician documented diagnosis of atopic dermatitis for at least 12 months before screening based on UK refinements of the Rajka and Hanifin criteria Exclusion Criteria: Part 1 (Healthy Participants): Participant has any known malignancy or history of malignancy, with the exception of basal cell carcinoma or squamous cell carcinoma in situ of the skin that has been treated with no evidence of recurrence within 6 months prior to the Screening Visit Part 1 (Healthy Participants): Participant currently has or has a history of any clinically significant cardiovascular disease, including but not limited to a history of angina or myocardial infarction, congestive heart failure, symptomatic atherosclerotic vascular disease, or arrhythmia. Part 2 (Asthma Participants): Participant has any known malignancy or history of malignancy, with the exception of basal cell carcinoma or squamous cell carcinoma in situ of the skin that has been treated with no evidence of recurrence within 6 months prior to the Screening Visit Part 2 (Asthma Participants): Participant has or have had a serious infection (eg, sepsis, pneumonia or pyelonephritis), or have been hospitalized or received IV antibiotics for a serious infection during the 4 months prior to the Screening Visit Part 2 (Atopic Dermatitis Participants): Participant has any known malignancy or history of malignancy, with the exception of basal cell carcinoma or squamous cell carcinoma in situ of the skin that has been treated with no evidence of recurrence within 6 months prior to the Screening Visit. Part 2 (Atopic Dermatitis Participants): Participant has or have had a serious infection (eg, sepsis, pneumonia or pyelonephritis), or have been hospitalized or received IV antibiotics for a serious infection during the 4 months prior to the Screening Visit

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: Dose 1<br>Drug CNTO7160 or Placebo administered IV infusion Dose 1. | Drug: Part 1: CNTO 7160<br>* Participants will receive Drug CNTO7160 administered IV infusion at escalating doses (with a starting dose of 0.001 mg/kg).<br>Drug: Part 1 and Part 2: Placebo<br>* Participants will receive single IV infusion of placebo matched to CNTO 7160.<br>|
| Experimental: Part 1: Dose 2<br>Drug CNTO7160 or Placebo administered IV infusion Dose 2. | Drug: Part 1: CNTO 7160<br>* Participants will receive Drug CNTO7160 administered IV infusion at escalating doses (with a starting dose of 0.001 mg/kg).<br>Drug: Part 1 and Part 2: Placebo<br>* Participants will receive single IV infusion of placebo matched to CNTO 7160.<br>|
| Experimental: Part 1: Dose 3<br>Drug CNTO7160 or Placebo administered IV infusion Dose 3. | Drug: Part 1: CNTO 7160<br>* Participants will receive Drug CNTO7160 administered IV infusion at escalating doses (with a starting dose of 0.001 mg/kg).<br>Drug: Part 1 and Part 2: Placebo<br>* Participants will receive single IV infusion of placebo matched to CNTO 7160.<br>|
| Experimental: Part 1: Dose 4<br>Drug CNTO7160 or Placebo administered IV infusion Dose 4. | Drug: Part 1: CNTO 7160<br>* Participants will receive Drug CNTO7160 administered IV infusion at escalating doses (with a starting dose of 0.001 mg/kg).<br>Drug: Part 1 and Part 2: Placebo<br>* Participants will receive single IV infusion of placebo matched to CNTO 7160.<br>|
| Experimental: Part 1: Dose 5<br>Drug CNTO7160 or Placebo administered IV infusion Dose 5. | Drug: Part 1: CNTO 7160<br>* Participants will receive Drug CNTO7160 administered IV infusion at escalating doses (with a starting dose of 0.001 mg/kg).<br>Drug: Part 1 and Part 2: Placebo<br>* Participants will receive single IV infusion of placebo matched to CNTO 7160.<br>|
| Experimental: Part 1: Dose 6<br>Drug CNTO7160 or Placebo administered IV infusion Dose 6. | Drug: Part 1: CNTO 7160<br>* Participants will receive Drug CNTO7160 administered IV infusion at escalating doses (with a starting dose of 0.001 mg/kg).<br>Drug: Part 1 and Part 2: Placebo<br>* Participants will receive single IV infusion of placebo matched to CNTO 7160.<br>|
| Experimental: Part 1: Dose 7<br>Drug CNTO7160 or Placebo administered IV infusion Dose 7. | Drug: Part 1: CNTO 7160<br>* Participants will receive Drug CNTO7160 administered IV infusion at escalating doses (with a starting dose of 0.001 mg/kg).<br>Drug: Part 1 and Part 2: Placebo<br>* Participants will receive single IV infusion of placebo matched to CNTO 7160.<br>|
| Experimental: Part 1: Dose 8<br>Drug CNTO7160 or Placebo administered IV infusion Dose 8. | Drug: Part 1: CNTO 7160<br>* Participants will receive Drug CNTO7160 administered IV infusion at escalating doses (with a starting dose of 0.001 mg/kg).<br>Drug: Part 1 and Part 2: Placebo<br>* Participants will receive single IV infusion of placebo matched to CNTO 7160.<br>|
| Experimental: Part 1: Dose 9<br>Drug CNTO7160 or Placebo administered IV infusion Dose 9. | Drug: Part 1: CNTO 7160<br>* Participants will receive Drug CNTO7160 administered IV infusion at escalating doses (with a starting dose of 0.001 mg/kg).<br>Drug: Part 1 and Part 2: Placebo<br>* Participants will receive single IV infusion of placebo matched to CNTO 7160.<br>|
| Experimental: Part 2 (Asthma): Dose 1<br>Drug CNTO 7160 or Placebo administered IV infusions Dose 1 (3 dose administrations over 4 weeks). | Drug: Part 2 (Asthma): CNTO 7160<br>* Participants will receive Drug CNTO 7160 administered IV infusions (3 dose administrations over 4 weeks).<br>Drug: Part 1 and Part 2: Placebo<br>* Participants will receive single IV infusion of placebo matched to CNTO 7160.<br>|
| Experimental: Part 2 (Asthma): Dose 2<br>Drug CNTO 7160 or Placebo administered IV infusions Dose 2 (3 dose administrations over 4 weeks). | Drug: Part 2 (Asthma): CNTO 7160<br>* Participants will receive Drug CNTO 7160 administered IV infusions (3 dose administrations over 4 weeks).<br>Drug: Part 1 and Part 2: Placebo<br>* Participants will receive single IV infusion of placebo matched to CNTO 7160.<br>|
| Experimental: Part 2 (Atopic Dermatitis): Dose 1<br>Drug CNTO 7160 or Placebo administered IV infusions Dose 1 (3 dose administrations over 4 weeks). | Drug: Part 2 (Atopic Dermatitis): CNTO 7160<br>* Participants will receive Drug CNTO 7160 administered IV infusions (3 dose administrations over 4 weeks).<br>Drug: Part 1 and Part 2: Placebo<br>* Participants will receive single IV infusion of placebo matched to CNTO 7160.<br>|
| Experimental: Part 2 (Atopic Dermatitis): Dose 2<br>Drug CNTO 7160 or Placebo administered IV infusions Dose 2 (3 dose administrations over 4 weeks). | Drug: Part 2 (Atopic Dermatitis): CNTO 7160<br>* Participants will receive Drug CNTO 7160 administered IV infusions (3 dose administrations over 4 weeks).<br>Drug: Part 1 and Part 2: Placebo<br>* Participants will receive single IV infusion of placebo matched to CNTO 7160.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Treatment Emergent Adverse Events (TEAEs) as a Measure of Safety and Tolerability of CNTO 7160 (Part 1) | The incidence of TEAEs from treatment until the last scheduled follow-up visit will be summarized by treatment group. | Through Week 17 | 
| Number of Participants with Treatment Emergent Adverse Events (TEAEs) as a Measure of Safety and Tolerability of CNTO 7160 (Part 2) | The incidence of TEAEs from treatment until the last scheduled follow-up visit will be summarized by treatment group. | Through Week 21 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Serum Concentration (Cmax) (Part 1) | Cmax (microgram per millileter [mcg/mL]) will be summarized by treatment group. | Up to Week 17 after dose | 
| Maximum Observed Serum Concentration (Cmax) (Part 2) | Cmax (mcg/mL) after the first and last dose will be summarized by treatment group. | Up to Week 21 after dose | 
| Area Under the Serum Time Curve [AUC(0-t) and AUC(0-infinity)] (Part 1) | AUC (mcg*day/mL) will be summarized by treatment group. | Up to Week 17 after dose | 
| Area Under the Serum Concentration Versus Time Curve [AUC(t1-t2)] (Part 2) | AUC (mcg*day/mL) will be summarized by treatment group. | Up to Week 21 after dose | 
| Number of Participants With Antibodies to CNTO 7160 (Part 1) | The incidence of participants with anti-CNTO 7160 antibodies will be summarized by treatment group. | Up to Week 17 | 
| Number of Participants with Antibodies to CNTO 7160 (Part 2) | The incidence of participants with anti-CNTO 7160 antibodies will be summarized by treatment group. | Up to Week 21 | 
| Change From Baseline in Immunoglobulin E (IgE) (Part 2) | Change from Baseline in immunoglobulin E (IgE) Concentration (international unit per millileter [IU/mL]) through Week 21 will be summarized by treatment group. | Baseline, Week 21 | 
| Change from Baseline in Chemokine (C-C motif) Ligand 17 (CCL17) (Part 2) | Change from Baseline in Chemokine (C-C motif) Ligand 17 (CCL17) concentration (picogram per millileter [pg/mL]) through Week 21 will be summarized by treatment group. | Baseline, Week 21 | 
| Change From Baseline in Forced Expiratory Volume in 1 second (FEV1) in Participants With Asthma | Changes in FEV1 (liter [L]) from baseline through end of follow up will be summarized by treatment group. | Baseline Up to week 21 | 
| Change From Baseline in Eczema Area Severity Index (EASI) in Participants With Atopic Dermatitis | Changes in EASI score from baseline through the end of follow up will be summarized by treatment group. | Baseline up to week 21 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Safety, Efficacy, CNTO 7160, Healthy, Asthma, Atopic Dermatitis