A Phase 3, Open-label, 52-week Study to Assess the Safety, Tolerability, and Efficacy of Rocatinlimab (AMG 451) in Adolescent Subjects Aged ≥ 12 to < 18 years With Moderate-to-severe Atopic Dermatitis (AD) (ROCKET-Orbit)
- Trial ID
- 2022-501535-16-00
- Protocol
- 20210263
- Sponsor
- Amgen Inc.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this Phase 3, open-label study is to describe the **safety** and **tolerability** of rocatinlimab in adolescent subjects aged 12 to less than 18 years with moderate-to-severe **Atopic Dermatitis (AD)**. This is clinically relevant as it aims to ensure that the treatment is safe and well-tolerated in this specific age group, which is crucial for the management of AD in adolescents.
Secondary objectives include:
- Describing the efficacy of rocatinlimab X mg at week 24, assessed using the validated Investigator’s Global Assessment for Atopic Dermatitis (vIGA-AD).
- Describing the efficacy of rocatinlimab X mg at week 24 using the Eczema Area and Severity Index (EASI).
- Describing the efficacy of rocatinlimab X mg at week 24, assessed using vIGA-AD with an additional assessment of morphology.
Participants
The clinical trial involves a total of **114 participants** diagnosed with **Atopic Dermatitis (AD)**, specifically targeting adolescents aged **12 to less than 18 years**. The study population includes both male and female subjects, with a focus on those with moderate-to-severe AD as indicated by a vIGA-AD score of 3 or higher. Participants are required to have a body weight of at least 40 kg and must have had AD for a minimum of six months prior to enrollment. The trial includes individuals who have shown an inadequate response to topical corticosteroids of medium or higher potency. Participants are expected to maintain a stable psychiatric treatment regimen, if applicable, for at least two months before the study. The selection process ensures that the trial population is representative of adolescents with significant AD involvement, as evidenced by an EASI score of 16 or higher. The trial is designed to assess the safety and tolerability of rocatinlimab in this specific demographic.
Plans and Procedures
The clinical trial is designed to evaluate the **safety** and **tolerability** of **rocatinlimab** in adolescents aged 12 to less than 18 years with moderate-to-severe **atopic dermatitis**. This is a Phase 3, open-label study with a duration of 52 weeks. Participants will receive **rocatinlimab** as a **solution for injection** administered via **subcutaneous use**. The trial will assess treatment-emergent serious adverse events as the primary endpoint. The study will involve several key visits, starting with an inclusion (screening) visit to confirm eligibility based on criteria such as a vIGA-AD score of 3 or higher, an EASI score of 16 or higher, and a body weight of at least 40 kg. Participants must also have a history of inadequate response to topical corticosteroids of medium or higher potency.
Following the screening, eligible participants will be enrolled and will attend regular follow-up visits to monitor their response to treatment and any adverse events. The study will conclude with an end-of-study visit to evaluate the overall outcomes and gather final data. The expected length of participant involvement is up to 52 weeks, with conditions for early termination including significant adverse events or withdrawal of consent. The trial is not categorized as low intervention, and the maximum daily dose of **rocatinlimab** is 300 mg, with a total maximum dose of 4200 mg over the treatment period. Participants' involvement may be terminated early if they experience treatment-emergent serious adverse events or if they no longer meet the study criteria.
Treatment
The clinical trial involves the administration of **rocatinlimab**, also known by its sponsor product code **AMG 451** and synonym **KHK4083**. Rocatinlimab is a **solution for injection** developed by Amgen Inc. It is classified as a protein of other origin. The pharmaceutical form of rocatinlimab is a solution intended for **subcutaneous use**. The maximum daily dose is 300 mg, with a total maximum dose of 4200 mg over the course of the study. The treatment period extends up to 52 weeks. The administration schedule and dosing are designed to ensure participant compliance, with regular monitoring throughout the trial.
In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus is solely on evaluating the safety, tolerability, and efficacy of rocatinlimab in adolescent subjects aged 12 to less than 18 years with moderate-to-severe atopic dermatitis. The trial is open-label, allowing for direct observation of the effects of the experimental medication without the use of blinding. Compliance with the dosing schedule is monitored to ensure adherence to the treatment protocol.
Efficacy
Efficacy in this clinical trial will be assessed through the evaluation of treatment-emergent serious adverse events as the primary endpoint. The study involves adolescent subjects aged 12 to less than 18 years with moderate-to-severe **Atopic Dermatitis**. The trial is designed as a Phase 3, open-label study with a duration of 52 weeks. The efficacy parameters will be collected and analyzed at specified timepoints throughout the study period. The assessment will utilize validated scales, including the vIGA-AD score, which ranges from 0 to 4, with a score of 3 indicating moderate and 4 indicating severe disease. Additionally, the EASI score, which must be ≥ 16 at both initial screening and day 1 pre-enrollment, will be used to further evaluate the severity of the condition. These measures will help determine the efficacy of Rocatinlimab (AMG 451) in improving the symptoms of Atopic Dermatitis in the study population.
Inclusion and Exclusion Criteria
Inclusion Criteria
- 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.
- Age ≥ 12 to < 18 years at day 1.
- 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.
- Body weight ≥ 40 kg at screening.
- Body weight ≥ 40 kg at day 1 pre-enrollment.
- 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.
- EASI score ≥ 16 at initial screening.
- EASI score ≥ 16 at day 1 pre-enrollment.
- vIGA-AD score ≥ 3 (on the 0 to 4 vIGA-AD scale, in which 3 is moderate and 4 is severe) at initial screening.
- 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.
- ≥ 10% BSA of AD involvement at initial screening.
- ≥ 10% BSA of AD involvement at day 1 pre-enrollment.
- 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
- 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).
- History of major immunologic reaction (eg, serum sickness, anaphylaxis, or anaphylactic reaction) to any other biologic product or any excipient of rocatinlimab.
- Known sensitivity to any of the products or components to be administered during dosing.
- 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.
- 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.
- Positive for hepatitis C virus (HCV) antibody at initial screening with confirmed positive HCV RNA.
- 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.
- 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
- 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.
- Active chronic or acute infection requiring treatment with systemic antibiotics, antiviral, antiparasitic, antiprotozoal, or antifungals within 4 weeks before day 1 pre-enrollment.
- Superficial skin infections within 2 weeks before day 1 pre-enrollment.
- Severe depression, poorly controlled schizophrenia, or subjects who have had an inpatient psychiatric admission within the last year.
- History of suicide attempt or suicidal ideation as evidenced by XXX
- Recent suicide attempt or suicidal ideation or behavior as XXX
- 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
- 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.
- Any cell depletion therapy within 12 months from initial screening or until cell count returns to normal before screening, whichever is longer.
- 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
- 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
- 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.
- 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.
- 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.
- 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.
- Female subjects who are breastfeeding or who plan to breastfeed while on study through 16 weeks after the last dose of investigational product.
- Female subjects planning to become pregnant while on study through 16 weeks after the last dose of investigational product.
- 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.
- Subject has known sensitivity to any of the products or components to be administered during dosing.
- 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.
- 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.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Austria | Not Yet Recruiting | 03 Apr 2023 | 6 |
 Denmark | Not Yet Recruiting | 03 Apr 2023 | 7 |
 Finland | Not Yet Recruiting | 03 Apr 2023 | 9 |
 Germany | Not Yet Recruiting | 03 Apr 2023 | 8 |
 Hungary | Not Yet Recruiting | 03 Apr 2023 | 6 |
 Italy | Not Yet Recruiting | 03 Apr 2023 | 6 |
 Poland | Not Yet Recruiting | 03 Apr 2023 | 9 |
 Portugal | Not Yet Recruiting | 03 Apr 2023 | 3 |
 Spain | Not Yet Recruiting | 03 Apr 2023 | 4 |