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

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

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).

Study Overview

• Status: Completed
• Conditions: Atopic Dermatitis
• Intervention / Treatment: Dietary supplement: Caffeine; Drug: Metoprolol; Drug: Midazolam; Drug: Warfarin; Dietary supplement: Vitamin K; Drug: Omeprazole; Drug: Rocatinlimab

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • North Hollywood, California, United States, 91606-1570
      • Velocity Clinical Research, North Hollywood
  • Florida
    • DeLand, Florida, United States, 32720-3134
      • Accel Research Sites (ACR)
    • Hialeah, Florida, United States, 33012-3618
      • Direct Helpers Research Center (DHRC)
  • Minnesota
    • Dilworth, Minnesota, United States, 56529
      • Axis Clinicals, LCC
  • Pennsylvania
    • Camp Hill, Pennsylvania, United States, 17011
      • DermDox Dermatology Centers, PC - Camp Hill
  • South Carolina
    • Spartanburg, South Carolina, United States, 29303-4225
      • Velocity Clinical Research -Spartanburg
  • Tennessee
    • Nashville, Tennessee, United States, 37203-1632
      • DermDox Dermatology Centers, PC - Sugarloaf

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female participant, aged 18 to 65 years
2. Diagnosis of AD, defined as diagnosis of AD for at least 6 months before signing of informed consent
3. Eczema Area Severity Index score ≥8 at the screening and Check-in
4. Investigator's Global Assessment (IGA) score ≥3 (on the 0 to 4 IGA scale) at screening and Check-in
5. ≥7% Body Surface Area of AD involvement at initial screening
6. 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).
7. Provide signed informed consent

Exclusion Criteria:

1. 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

2. The use of any of the following treatments within 4 weeks before Check-in:

   • Systemic corticosteroids
   • Immunosuppressive/immunomodulating drugs

3. The use of any of the following treatments within one week before Check-in:

   1. Topical corticosteroids of any super-high potency
   2. Topical phosphodiesterase 4 (PDE4) inhibitors
   3. Phototherapy
4. 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.

5. Any contraindication to one or more of the following drugs, according to the applicable labeling:

   • Midazolam
   • Omeprazole
   • Warfarin (and Vitamin K)
   • Caffeine
   • Metoprolol

6. 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
7. 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)
8. Smoke more than 10 cigarettes or use the equivalent (as determined by site staff) tobacco- or nicotine-containing products per day and unwilling to adhere to smoking restrictions.
9. Poor metabolizers for CYP2C9, CYP2C19, or CYP2D6 based on genotyping

10. 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

11. Active, chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antiprotozoals, or antifungals at screening or Check-in
12. Superficial skin infections, including tinea infections, within 2 weeks prior to Check-in
13. History of acquired, common variable, primary or secondary immunodeficiency
14. 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.
15. 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)
16. 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.
17. 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
18. 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
19. Unwilling to adhere to contraceptive requirements through 18 weeks after the end of study visit
20. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Rocatinlimab and CYP450 Substrates; 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.

Dietary supplement: Caffeine; Oral liquid; Other Names: Caffeine Citrate; Drug: Metoprolol; Oral tablet; Other Names: Metoprolol Tartrate; Drug: Midazolam; Oral liquid; Other Names: Midazolam Hydrochloride; Drug: Warfarin; Oral tablet; Other Names: Warfarin Sodium; Dietary supplement: Vitamin K; Oral tablet; Drug: Omeprazole; Oral capsule; Other Names: Omeprazole magnesium; Drug: Rocatinlimab; Subcutaneous injection; Other Names: AMG 451

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum Observed Serum Concentration (Cmax) of CYP450 Substrate	Day 1
Cmax of CYP450 Substrate	Day 120
Area Under the Serum Concentration-Time Curve from Time Zero to Time of Last Quantifiable Concentration (AUClast) of CYP450 Substrate	Day 1
AUClast of CYP450 Substrate	Day 120
Area Under the Serum Concentration-Time Curve from Time Zero to Infinity (AUCinf) of CYP450 Substrate	Day 1
AUCinf of CYP450 Substrate	Day 120

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of Participants with Treatment-emergent Adverse Events (TEAEs)	Up to Day 238
Number of Participants with Serious Adverse Events (SAEs)	Up to Day 238
Number of Participants with Anti-rocatinlimab Antibody Formation	Up to Day 238

Collaborators and Investigators

• Sponsor: Amgen
• Investigators: Study Director: MD, Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): June 3, 2023
• Primary Completion (Actual): August 28, 2024
• Study Completion (Actual): February 12, 2025

Study Registration Dates

• First Submitted: May 26, 2023
• First Submitted That Met QC Criteria: May 26, 2023
• First Posted (Actual): June 6, 2023

Study Record Updates

• Last Update Posted (Actual): December 23, 2025
• Last Update Submitted That Met QC Criteria: December 19, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: AMG 451; Rocatinlimab; Moderate to Severe Atopic Dermatitis; Cytochrome P450 (CYP450) Substrates
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Immune System Diseases; Hypersensitivity, Immediate; Hypersensitivity; Skin Diseases; Skin Diseases, Genetic; Skin Diseases, Eczematous; Dermatitis; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin and Connective Tissue Diseases; Dermatitis, Atopic; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pyrans; Hydrocarbons; Hydrocarbons, Cyclic; Terpenes; Alkaloids; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Amines; Purinones; Purines; Diterpenes; Alcohols; Benzazepines; Phenoxypropanolamines; Propanolamines; Amino Alcohols; Propanols; Coumarins; Benzopyrans; Benzodiazepines; Naphthoquinones; Phytol; Xanthines; 4-Hydroxycoumarins; Midazolam; Metoprolol; Vitamin K; Warfarin; Caffeine; Omeprazole; caffeine citrate
• Other Study ID Numbers: 20210147

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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 Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No