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Study to Investigate the Effect of Rocatinlimab (AMG 451) on the Pharmacokinetics of Multiple Cytochrome P450 (CYP450) Substrates in Participants With Moderate to Severe Atopic Dermatitis

Primary Purpose

Atopic Dermatitis

Status
Recruiting
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Caffeine
Metoprolol
Midazolam
Warfarin
Vitamin K
Omeprazole
Rocatinlimab
Sponsored by
Amgen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Atopic Dermatitis focused on measuring Moderate to Severe Atopic Dermatitis, Rocatinlimab, AMG 451, Cytochrome P450 (CYP450) Substrates

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Male or female participant, aged 18 to 65 years Diagnosis of AD, defined as diagnosis of AD for at least 6 months before signing of informed consent Eczema Area Severity Index score ≥12 at the screening and Check-in Investigator's Global Assessment (IGA) score ≥3 (on the 0 to 4 IGA scale) at screening and Check-in ≥7% Body Surface Area of AD involvement at initial screening History of inadequate response to topical corticosteroid therapy (TCS) of medium to higher potency within 6 months (with or without topical calcineurin inhibitors [TCI]) or for whom topical treatments are otherwise medically inadvisable (eg, because of important side effects or safety risks). Provide signed informed consent Exclusion Criteria: Have previously completed or withdrawn from this study or any other study investigating rocatinlimab or have previously received a dose of an investigational drug within the past 90 days or 5 half-lives, whichever is longer, prior to Check-in The use of any of the following treatments within 4 weeks before Check-in: Systemic corticosteroids Immunosuppressive/immunomodulating drugs The use of any of the following treatments within one week before Check-in: Topical corticosteroids of high or ultrahigh potency Topical phosphodiesterase 4 (PDE4) inhibitors Other topical immunosuppressive agents Phototherapy Any combination containing any of the above agents Administration, within 14 days before baseline or within a period of 5 times the elimination half-life of the medication before baseline, whichever is longer, of any medication that is a known inducer or inhibitor of either one or more of the following cytochrome P450 (CYP) enzymes: CYP3A4, CYP2C19, CYP2C9, CYP2D6, and CYP1A2. Participants who are on any of these medications at the time of screening and cannot be safely taken off these medications will be excluded from the study. Any contraindication to one or more of the following drugs, according to the applicable labeling: Midazolam Omeprazole Warfarin (and Vitamin K) Caffeine Metoprolol Consumption of any 1 or more of the following food items and/or beverages within 1 week prior to Check-in: Grapefruit or grapefruit juice, apple or apple juice, orange or orange juice, lemons or lemon juice, limes or lime juice Vegetables from the mustard green family (eg, broccoli) Charbroiled meats Caffeinated beverages, foods or drugs containing caffeine History of alcoholism or drug/chemical abuse within 1 year prior to Check-in or regular alcohol consumption (>14 units per week for males and >7 units for females) Use of tobacco- or nicotine-containing products within 6 months prior to Check-in. Poor metabolizers for CYP2C9, CYP2C19, or CYP2D6 based on genotyping Presence of any one or more of the following lab abnormalities at screening or Check-in: • Platelet count <100k /µL, international normalized ratio (INR)>1.2, prothrombin time (PT)>13.5 sec or partial thromboplastin time (PTT)>35 sec Active, chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antiprotozoals, or antifungals at screening or Check-in Superficial skin infections, including tinea infections, within 2 weeks prior to Check-in History of acquired, common variable, primary or secondary immunodeficiency Positive hepatitis B or hepatitis C panel and/or positive human immunodeficiency virus test, at screening as per Center for Disease Control interpretation. Participants whose hepatitis B and C results are compatible with prior immunity (resulting from inoculation) may be included. Participants with positive hepatitis B core antibody will be excluded. Active malignancy, multiple myeloma, myeloproliferative or lymphoproliferative disorder, or a history of any of these conditions within 5 years prior to informed consent (except curatively treated in situ cervical carcinoma, cutaneous basal cell carcinoma, or cutaneous squamous cell carcinoma) Diagnosis of a helminth parasitic infection within 6 months prior to screening that had not been treated with or failed to respond to standard of care therapy. History of suicidal ideation (thoughts), suicide-related behaviors, suicide attempt(s), depression or major psychiatric illness within 6 months prior to signing the informed consent Female participants who are pregnant, breastfeeding, or planning to become pregnant or breastfeed during the study through 18 weeks after the end of study visit Unwilling to adhere to contraceptive requirements through 18 weeks after the end of study visit Male participant with a pregnant partner or partner planning to become pregnant while the participant is on study through 18 weeks after the end of study visit

Sites / Locations

  • Axis ClinicalRecruiting
  • DermDox Centers for DermatologyRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Rocatinlimab and CYP450 Substrates

Arm Description

A single oral dose of a CYP450 substrates cocktail which will include caffeine, metoprolol, midazolam, warfarin (with vitamin K), and omeprazole will be administered on Day 1. A single dose of rocatinlimab will then be administered on Days 8, 22, 36, 64, and 92. A single oral dose of CYP450 substrates cocktail in combination with a single dose of rocatinlimab will then be administered on Day 120.

Outcomes

Primary Outcome Measures

Maximum Observed Serum Concentration (Cmax) of CYP450 Substrate
Cmax of CYP450 Substrate
Area Under the Serum Concentration-Time Curve from Time Zero to Time of Last Quantifiable Concentration (AUClast) of CYP450 Substrate
AUClast of CYP450 Substrate
Area Under the Serum Concentration-Time Curve from Time Zero to Infinity (AUCinf) of CYP450 Substrate
AUCinf of CYP450 Substrate

Secondary Outcome Measures

Number of Participants with Treatment-emergent Adverse Events (TEAEs)
Number of Participants with Serious Adverse Events (SAEs)
Number of Participants with Anti-rocatinlimab Antibody Formation

Full Information

First Posted
May 26, 2023
Last Updated
September 22, 2023
Sponsor
Amgen
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1. Study Identification

Unique Protocol Identification Number
NCT05891119
Brief Title
Study to Investigate the Effect of Rocatinlimab (AMG 451) on the Pharmacokinetics of Multiple Cytochrome P450 (CYP450) Substrates in Participants With Moderate to Severe Atopic Dermatitis
Official Title
A Phase 1, Open-label, Drug-Drug Interaction Study to Investigate the Effect of Rocatinlimab (AMG 451) on the Pharmacokinetics of Multiple CYP450 Substrates in Patients With Moderate to Severe Atopic Dermatitis
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 3, 2023 (Actual)
Primary Completion Date
August 2, 2024 (Anticipated)
Study Completion Date
November 29, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amgen

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The primary objective of the study is to evaluate the pharmacokinetics (PK) of multiple cytochrome P450 (CYP450) substrates alone and in combination with rocatinlimab in participants with moderate to severe atopic dermatitis (AD).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Atopic Dermatitis
Keywords
Moderate to Severe Atopic Dermatitis, Rocatinlimab, AMG 451, Cytochrome P450 (CYP450) Substrates

7. Study Design

Primary Purpose
Basic Science
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Rocatinlimab and CYP450 Substrates
Arm Type
Experimental
Arm Description
A single oral dose of a CYP450 substrates cocktail which will include caffeine, metoprolol, midazolam, warfarin (with vitamin K), and omeprazole will be administered on Day 1. A single dose of rocatinlimab will then be administered on Days 8, 22, 36, 64, and 92. A single oral dose of CYP450 substrates cocktail in combination with a single dose of rocatinlimab will then be administered on Day 120.
Intervention Type
Dietary Supplement
Intervention Name(s)
Caffeine
Other Intervention Name(s)
Caffeine Citrate
Intervention Description
Oral liquid
Intervention Type
Drug
Intervention Name(s)
Metoprolol
Other Intervention Name(s)
Metoprolol Tartrate
Intervention Description
Oral tablet
Intervention Type
Drug
Intervention Name(s)
Midazolam
Other Intervention Name(s)
Midazolam Hydrochloride
Intervention Description
Oral liquid
Intervention Type
Drug
Intervention Name(s)
Warfarin
Other Intervention Name(s)
Warfarin Sodium
Intervention Description
Oral tablet
Intervention Type
Dietary Supplement
Intervention Name(s)
Vitamin K
Intervention Description
Oral tablet
Intervention Type
Drug
Intervention Name(s)
Omeprazole
Other Intervention Name(s)
Omeprazole magnesium
Intervention Description
Oral capsule
Intervention Type
Drug
Intervention Name(s)
Rocatinlimab
Other Intervention Name(s)
AMG 451
Intervention Description
Subcutaneous injection
Primary Outcome Measure Information:
Title
Maximum Observed Serum Concentration (Cmax) of CYP450 Substrate
Time Frame
Day 1
Title
Cmax of CYP450 Substrate
Time Frame
Day 120
Title
Area Under the Serum Concentration-Time Curve from Time Zero to Time of Last Quantifiable Concentration (AUClast) of CYP450 Substrate
Time Frame
Day 1
Title
AUClast of CYP450 Substrate
Time Frame
Day 120
Title
Area Under the Serum Concentration-Time Curve from Time Zero to Infinity (AUCinf) of CYP450 Substrate
Time Frame
Day 1
Title
AUCinf of CYP450 Substrate
Time Frame
Day 120
Secondary Outcome Measure Information:
Title
Number of Participants with Treatment-emergent Adverse Events (TEAEs)
Time Frame
Up to Day 238
Title
Number of Participants with Serious Adverse Events (SAEs)
Time Frame
Up to Day 238
Title
Number of Participants with Anti-rocatinlimab Antibody Formation
Time Frame
Up to Day 238

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male or female participant, aged 18 to 65 years Diagnosis of AD, defined as diagnosis of AD for at least 6 months before signing of informed consent Eczema Area Severity Index score ≥12 at the screening and Check-in Investigator's Global Assessment (IGA) score ≥3 (on the 0 to 4 IGA scale) at screening and Check-in ≥7% Body Surface Area of AD involvement at initial screening History of inadequate response to topical corticosteroid therapy (TCS) of medium to higher potency within 6 months (with or without topical calcineurin inhibitors [TCI]) or for whom topical treatments are otherwise medically inadvisable (eg, because of important side effects or safety risks). Provide signed informed consent Exclusion Criteria: Have previously completed or withdrawn from this study or any other study investigating rocatinlimab or have previously received a dose of an investigational drug within the past 90 days or 5 half-lives, whichever is longer, prior to Check-in The use of any of the following treatments within 4 weeks before Check-in: Systemic corticosteroids Immunosuppressive/immunomodulating drugs The use of any of the following treatments within one week before Check-in: Topical corticosteroids of high or ultrahigh potency Topical phosphodiesterase 4 (PDE4) inhibitors Other topical immunosuppressive agents Phototherapy Any combination containing any of the above agents Administration, within 14 days before baseline or within a period of 5 times the elimination half-life of the medication before baseline, whichever is longer, of any medication that is a known inducer or inhibitor of either one or more of the following cytochrome P450 (CYP) enzymes: CYP3A4, CYP2C19, CYP2C9, CYP2D6, and CYP1A2. Participants who are on any of these medications at the time of screening and cannot be safely taken off these medications will be excluded from the study. Any contraindication to one or more of the following drugs, according to the applicable labeling: Midazolam Omeprazole Warfarin (and Vitamin K) Caffeine Metoprolol Consumption of any 1 or more of the following food items and/or beverages within 1 week prior to Check-in: Grapefruit or grapefruit juice, apple or apple juice, orange or orange juice, lemons or lemon juice, limes or lime juice Vegetables from the mustard green family (eg, broccoli) Charbroiled meats Caffeinated beverages, foods or drugs containing caffeine History of alcoholism or drug/chemical abuse within 1 year prior to Check-in or regular alcohol consumption (>14 units per week for males and >7 units for females) Use of tobacco- or nicotine-containing products within 6 months prior to Check-in. Poor metabolizers for CYP2C9, CYP2C19, or CYP2D6 based on genotyping Presence of any one or more of the following lab abnormalities at screening or Check-in: • Platelet count <100k /µL, international normalized ratio (INR)>1.2, prothrombin time (PT)>13.5 sec or partial thromboplastin time (PTT)>35 sec Active, chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antiprotozoals, or antifungals at screening or Check-in Superficial skin infections, including tinea infections, within 2 weeks prior to Check-in History of acquired, common variable, primary or secondary immunodeficiency Positive hepatitis B or hepatitis C panel and/or positive human immunodeficiency virus test, at screening as per Center for Disease Control interpretation. Participants whose hepatitis B and C results are compatible with prior immunity (resulting from inoculation) may be included. Participants with positive hepatitis B core antibody will be excluded. Active malignancy, multiple myeloma, myeloproliferative or lymphoproliferative disorder, or a history of any of these conditions within 5 years prior to informed consent (except curatively treated in situ cervical carcinoma, cutaneous basal cell carcinoma, or cutaneous squamous cell carcinoma) Diagnosis of a helminth parasitic infection within 6 months prior to screening that had not been treated with or failed to respond to standard of care therapy. History of suicidal ideation (thoughts), suicide-related behaviors, suicide attempt(s), depression or major psychiatric illness within 6 months prior to signing the informed consent Female participants who are pregnant, breastfeeding, or planning to become pregnant or breastfeed during the study through 18 weeks after the end of study visit Unwilling to adhere to contraceptive requirements through 18 weeks after the end of study visit Male participant with a pregnant partner or partner planning to become pregnant while the participant is on study through 18 weeks after the end of study visit
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Amgen Call Center
Phone
866-572-6436
Email
medinfo@amgen.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MD
Organizational Affiliation
Amgen
Official's Role
Study Director
Facility Information:
Facility Name
Axis Clinical
City
Dilworth
State/Province
Minnesota
ZIP/Postal Code
56529
Country
United States
Individual Site Status
Recruiting
Facility Contact:
Phone
913-314-6755
Facility Name
DermDox Centers for Dermatology
City
Camp Hill
State/Province
Pennsylvania
ZIP/Postal Code
17011
Country
United States
Individual Site Status
Recruiting
Facility Contact:
Phone
717-439-6900

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
IPD Sharing Time Frame
Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
IPD Sharing Access Criteria
Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
IPD Sharing URL
http://www.amgen.com/datasharing
Links:
URL
http://www.amgentrials.com
Description
AmgenTrials clinical trials website

Learn more about this trial

Study to Investigate the Effect of Rocatinlimab (AMG 451) on the Pharmacokinetics of Multiple Cytochrome P450 (CYP450) Substrates in Participants With Moderate to Severe Atopic Dermatitis

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