Phase 3 Study Assessing Rocatinlimab (AMG 451) in Adolescent Subjects With Moderate-to-severe Atopic Dermatitis (AD) (ROCKET-Orbit)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Amgen Inc.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Decision date (initial)

2023-03-27

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Amgen Inc.

External identifiers

EU CT number

2022-501535-16-00

WHO UTN

U1111-1281-0735

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Safety, Efficacy

To describe the safety and tolerability of rocatinlimab in adolescents with moderate-to-severe AD

Secondary objectives 3

1. To describe the efficacy of rocatinlimab X mg at week 24, assessed using validated Investigator’s Global Assessment for Atopic Dermatitis (vIGA-AD)
2. To describe the efficacy of rocatinlimab X mg at week 24 using EASI
3. To describe the efficacy of rocatinlimab Xmg at week 24, assessed using vIGA-AD with an additional assessment of morphology

Conditions and MedDRA coding

Atopic Dermatitis (AD)

Study design 1 period

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-002886-PIP01-20

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Subject’s legally authorized representative has provided informed consent when the subject is legally too young to provide informed consent and the subject has provided written assent based on local regulations and/or guidelines prior to any study-specific activities/procedures being initiated.
2. Age ≥ 12 to < 18 years at day 1.
3. Subject has a diagnosis of AD (according to American Academy of Dermatology Consensus Criteria [Eichenfield, 2014]) that has been present for at least 6 months before signing of informed consent.
4. Body weight ≥ 40 kg at screening.
5. Body weight ≥ 40 kg at day 1 pre-enrollment.
6. Prior to informed consent, history of inadequate response to TCS of medium or higher potency within 6 months (with or without TCI as appropriate). • Inadequate response is defined as failure to achieve and maintain remission or a low disease activity state (comparable to vIGA-AD score of 0 = clear to 2 = mild) despite treatment with a daily regimen of TCS of medium or higher potency with or without TCI as appropriate), applied for at least 28 days or the maximum duration recommended by the product prescribing information (eg, 14 days for super-high potent TCS), whichever is shorter.
7. EASI score ≥ 16 at initial screening.
8. EASI score ≥ 16 at day 1 pre-enrollment.
9. vIGA-AD score ≥ 3 (on the 0 to 4 vIGA-AD scale, in which 3 is moderate and 4 is severe) at initial screening.
10. vIGA-AD score ≥ 3 (on the 0 to 4 vIGA-AD scale, in which 3 is moderate and 4 is severe) at day 1 pre-enrollment.
11. ≥ 10% BSA of AD involvement at initial screening.
12. ≥ 10% BSA of AD involvement at day 1 pre-enrollment.
13. Subjects who are receiving psychiatric treatment regimen need to be stable on treatment for at least 2 months prior to study day 1 pre-enrollment.

Exclusion criteria 29

1. 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).
2. History of major immunologic reaction (eg, serum sickness, anaphylaxis, or anaphylactic reaction) to any other biologic product or any excipient of rocatinlimab.
3. Known sensitivity to any of the products or components to be administered during dosing.
4. Diagnosis of a helminth parasitic infection within 6 months prior to day 1 pre-enrollment that had not been treated with or had failed to respond to standard of care therapy.
5. Evidence of human immunodeficiency virus (HIV) infection or positive for HIV antibodies at initial screening or current acquired, common variable or inhibited, primary or secondary immunodeficiency.
6. Positive for hepatitis C virus (HCV) antibody at initial screening with confirmed positive HCV RNA.
7. Active and non-virally suppressed hepatitis B infection at initial screening, defined as detectable hepatitis B DNA polymerase chain reaction (PCR) test in a subject with detectable hepatitis B Surface Antigen (HBsAg) and/or antibodies to hepatitis B core (anti-HBc). Subjects with detectable HBsAg are required to be virally suppressed with an approved hepatitis B antiviral therapy during the study.
8. Positive or indeterminate XXX from central laboratory at initial screening. Exception: A positive or indeterminate XXX test is allowed if ALL of the following are present at initial screening: • No symptoms of tuberculosis (TB) as XXX • Documented history of a completed course of adequate prophylaxis (completed treatment for latent TB per local standard of care prior to start of investigational product) • No known exposure to a case of active TB after most recent prophylaxis • No evidence of active TB on XXX
9. A corrected QT interval (QTc) of > 450 msec in males or > 470 msec in females at initial screening as assessed by the investigator, or history of long QT syndrome.
10. Active chronic or acute infection requiring treatment with systemic antibiotics, antiviral, antiparasitic, antiprotozoal, or antifungals within 4 weeks before day 1 pre-enrollment.
11. Superficial skin infections within 2 weeks before day 1 pre-enrollment.
12. Severe depression, poorly controlled schizophrenia, or subjects who have had an inpatient psychiatric admission within the last year.
13. History of suicide attempt or suicidal ideation as evidenced by XXX
14. Recent suicide attempt or suicidal ideation or behavior as XXX
15. Any of the following laboratory abnormalities at initial screening: • Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m^2 • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥ 2.5 times the upper limit of normal (ULN) • Neutrophil count < 1.5 x 10^3/µL
16. Treatment with a biologic immunosuppressive or immunomodulatory therapy for AD or any other autoimmune, inflammatory, or allergic condition XXX within 12 weeks or 5 half-lives, whichever is longer, prior to day 1 pre-enrollment.
17. Any cell depletion therapy within 12 months from initial screening or until cell count returns to normal before screening, whichever is longer.
18. Treatment with any of the following medications or therapies within 4 weeks or 5 half-lives, whichever is longer, prior to day 1 pre-enrollment: • Systemic corticosteroids (inhaled corticosteroids, intra-articular steroid injection, eye, ear, or nasal drops containing corticosteroids are allowed, suppositories, thalidomide, or enemas containing corticosteroids are not allowed) • Systemic treatment with methotrexate, mycophenolate, calcineurin inhibitors, thalidomide, or other systemic immunosuppressants • Phototherapy • Oral or topical JAK inhibitors • TCS with high- or super high-potency
19. Treatment with any of the following agents within 1 week before day 1 pre-enrollment: • TCS • TCI • Anti-pruritic agents (e.g., crotamiton) or antihistamines used for treatment of pruritus • Topical phosphodiesterase type 4 (PDE4) inhibitors • Other topical immunosuppressive agents • Combination topical agents containing a corticosteroid or calcineurin-inhibiting component
20. Treatment with live virus including live attenuated vaccination 12 weeks prior to day 1. Inactive vaccination (eg, non-live or nonreplicating agent), including COVID-19 vaccination, is allowed.
21. Previous participation in a study including rocatinlimab (formerly KHK4083 or AMG 451) or any therapy selectively targeting OX40/OX40L and receipt of active investigational product.
22. Currently receiving treatment in another investigational device or drug study, or less than 30 days (16 weeks for Japan) since ending treatment on another investigational device or drug study(ies). Other investigational procedures while participating in this study are excluded.
23. Female subjects of childbearing potential unwilling to use protocol specified method of contraception see Appendix 5 (Section 11.5) during treatment and for an additional 16 weeks after the last dose of investigational product.
24. Female subjects who are breastfeeding or who plan to breastfeed while on study through 16 weeks after the last dose of investigational product.
25. Female subjects planning to become pregnant while on study through 16 weeks after the last dose of investigational product.
26. Female subjects of childbearing potential with a positive pregnancy test assessed at initial screening and day 1 pre-enrollment by a highly sensitive serum or urine pregnancy test, respectively.
27. Subject has known sensitivity to any of the products or components to be administered during dosing.
28. Subject likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures (e.g., Clinical Outcome Assessments) to the best of the subject and investigator’s knowledge.
29. History or evidence of any other clinically significant disorder (including concomitant dermatologic conditions such as psoriasis), or disease, including non-AD dermatologic conditions (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Treatment-emergent serious adverse events

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Amgen Inc.

Sponsor organisation

Amgen Inc.

Address

1 Amgen Center Drive

City

Thousand Oaks

Postcode

91320-1799

Country

United States

Scientific contact point

Organisation

Amgen Inc.

Contact name

Medical Information

Public contact point

Organisation

Amgen Inc.

Contact name

Medical Information

Third parties 5

Locations

9 EU/EEA countries · 21 investigational sites

By country

Investigational sites

Application history

1 submissions — initial application plus substantial / non-substantial modifications