Clinical trial NCT05891119: 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
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Atopic Dermatitis
Keywords: Moderate to Severe Atopic Dermatitis
Rocatinlimab
AMG 451
Cytochrome P450 (CYP450) Substrates
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2023-06-06
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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).


Eligibility criteria: 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 Have previously completed or withdrawn from this study or any other study investigating rocatinlimab or have previously received a dose of an investigational drug within the past 90 days or 5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

Primary outcomes:
measure: Maximum Observed Serum Concentration (Cmax) of CYP450 Substrate
timeFrame: Day 1
measure: Cmax of CYP450 Substrate
timeFrame: Day 120
measure: Area Under the Serum Concentration-Time Curve from Time Zero to Time of Last Quantifiable Concentration (AUClast) of CYP450 Substrate
timeFrame: Day 1
measure: AUClast of CYP450 Substrate
timeFrame: Day 120
measure: Area Under the Serum Concentration-Time Curve from Time Zero to Infinity (AUCinf) of CYP450 Substrate
timeFrame: Day 1
measure: AUCinf of CYP450 Substrate
timeFrame: Day 120
Secondary outcomes:
measure: Number of Participants with Treatment-emergent Adverse Events (TEAEs)
timeFrame: Up to Day 238
measure: Number of Participants with Serious Adverse Events (SAEs)
timeFrame: Up to Day 238
measure: Number of Participants with Anti-rocatinlimab Antibody Formation
timeFrame: Up to Day 238
Other outcomes:
Locations:
city: North Hollywood
country: United States
facility: Velocity Clinical Research, North Hollywood
state: California
city: DeLand
country: United States
facility: Accel Research Sites (ACR)
state: Florida
city: Hialeah
country: United States
facility: Direct Helpers Research Center (DHRC)
state: Florida
city: Dilworth
country: United States
facility: Axis Clinicals, LCC
state: Minnesota
city: Camp Hill
country: United States
facility: DermDox Dermatology Centers, PC - Camp Hill
state: Pennsylvania
city: Spartanburg
country: United States
facility: Velocity Clinical Research -Spartanburg
state: South Carolina
city: Nashville
country: United States
facility: DermDox Dermatology Centers, PC - Sugarloaf
state: Tennessee
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: