Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Efavaleukin Alfa in Participants With Systemic Lupus Erythematosus

NCT03451422 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 201701032017-002564-40
• Study Type: interventional
• Target: 35
• Locations: 4 countries
• Sites: 15

Brief Summary

To evaluate the safety and tolerability of subcutaneous (SC) dose administrations of Efavaleukin Alfa in participants with systemic lupus erythematosus (SLE).

Conditions

Systemic Lupus Erythematosus

Keywords

Efavaleukin Alfa; Systemic lupus erythematosus; Phase 1b

Outcome Measures

Primary Outcomes (1)

• Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)

  A TEAE was defined as any adverse event (AE) starting on or after the first dose of investigational product through to the safety follow-up visit. Any clinically significant changes in physical examinations, vital signs, and clinical laboratory test results were recorded as AEs.

  Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up)

Secondary Outcomes (5)

• Maximum Observed Concentration (Cmax) for AMG 592

  Day 1 (pre-dose) and 6 to 72 hours post-dose, and Days 8, 11, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, Day 85 (pre-dose) and 6 to 72 hours post-dose, and Days 92, 99, 113 and 127

• Time of Cmax (Tmax) for AMG 592

  Day 1 (pre-dose) and 6 to 72 hours post-dose, and Days 8, 11, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, Day 85 (pre-dose) and 6 to 72 hours post-dose, and Days 92, 99, 113 and 127

• Area Under the Concentration-time Curve Over a Dosing Interval (AUCtau) for AMG 592

  Day 1 (pre-dose) and 6 to 72 hours post-dose, and Days 8, 11, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, Day 85 (pre-dose) and 6 to 72 hours post-dose, and Days 92, 99, 113 and 127

• Number of Participants With Anti-AMG 592 Binding Antibodies and Anti-Interleukin (IL-2) Binding Antibodies

  Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up)

• Number of Participants With Anti-AMG 592 Neutralizing Antibodies and Anti-IL-2 Neutralizing Antibodies

  Day 1 up to end of study, maximum of 18 weeks (12-week double-blind treatment, 6-week safety follow-up)

Study Arms (2)

Efavaleukin Alfa

EXPERIMENTAL

Approximately 29 participants will be randomized in a 5:2 ratio (cohorts 1, 2, and 3) or in a 3:1 ratio (cohorts 4 and 5) to Efavaleukin Alfa or placebo in addition to standard of care therapy. Efavaleukin Alfa or placebo will be administered either weekly (QW) or biweekly (Q2W).

Drug: Efavaleukin Alfa

Placebo

PLACEBO COMPARATOR

Approximately 29 participants will be randomized in a 5:2 ratio (cohorts 1, 2, and 3) or in a 3:1 ratio (cohorts 4 and 5) to Efavaleukin Alfa or placebo in addition to standard of care therapy. Efavaleukin Alfa or placebo will be administered either weekly (QW) or biweekly (Q2W).

Drug: Placebo

Interventions

Efavaleukin Alfa DRUG

Efavaleukin Alfa will be administered by subcutaneous (SC) injection in the abdomen, thigh or upper arm.

Efavaleukin Alfa

Placebo DRUG

The placebo will be administered by subcutaneous (SC) injection in the abdomen, thigh or upper arm.

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants are eligible to be included in the study only if all of the following criteria apply:
• Participant has provided informed consent prior to initiation of any study specific activities/procedures.
• Age ≥ 18 years to ≤ 70 years at screening.
• Fulfills diagnostic criteria for SLE according to the Systemic Lupus International Collaborating Clinics (SLICC) criteria or by at least 4 of the 11 criteria of the 1997 American College of Rheumatology (ACR) classification criteria for SLE, with a history of at least one of the following:
• Antinuclear antibody ≥ 1:80; or
• Elevated anti-dsDNA antibodies
• May be taking ≤ 3 systemic SLE treatments and the dose must be stable for ≥ 4 weeks prior to day 1.
• Prednisone dose ≤ 20 mg daily (or other equivalent oral corticosteroid) with stable dose ≥ 2 weeks prior to day 1.
• Normal or clinically acceptable ECG values (12-lead reporting ventricular rate and PR, QRS, QT and QTc interval) at screening and baseline based on opinion of the investigator.
• Immunizations (tetanus, diphtheria, pertussis \[Td/Tdap\]), seasonal influenza (during flu season), and pneumococcal (polysaccharide) vaccinations\] up to date per local standards as determined by the investigator.

You may not qualify if:

• Participants are excluded from the study if any of the following criteria apply.
• Disease Related
• \- History of lupus nephritis requiring induction therapy and/or lupus cerebritis ≤ 1 year prior to screening.
• Other Medical Conditions
• Diagnosis of inflammatory joint or skin disease other than SLE which would interfere with SLE disease assessment based on investigator judgement.
• Diagnosis of fibromyalgia which would interfere with SLE assessment according to the investigator.
• Prosthetic joint infection within 3 years of screening or native joint infection within 1 year prior to screening.
• Active infection (including chronic or localized infections) for which anti-infectives were indicated within 4 weeks prior to day 1 OR presence of serious infection, defined as requiring hospitalization or intravenous anti-infectives within 8 weeks prior to day 1.
• Known history of active tuberculosis.
• Positive test for tuberculosis during screening defined as either:
• positive purified protein derivative (PPD) (≥ 5 mm of induration at 48 to 72 hours after test is placed) OR positive Quantiferon test
• a positive PPD and a history of Bacillus Calmette-Guérin vaccination are allowed with a negative Quantiferon test and negative chest X-ray.
• a positive PPD test (without a history of Bacillus Calmette-Guérin vaccination) or a positive or indeterminate Quantiferon test are allowed if they have ALL of the following at screening:
• no symptoms per tuberculosis worksheet provided by Amgen
• documented history of a completed course of adequate prophylaxis (completed treatment for latent tuberculosis per local standard of care prior to the start of investigational product)

Sponsors & Collaborators

• Amgen: lead

Study Sites (15)

Pinnacle Research Group LLC

Anniston, Alabama, 36207, United States

Location

Wallace Rheumatic Studies Center LLC

Beverly Hills, California, 90211, United States

Location

Translational Clinical Research LLC

Aventura, Florida, 33180, United States

Location

Northwell Health

Great Neck, New York, 11021, United States

Location

Altoona Center for Clinical Research

Duncansville, Pennsylvania, 16635, United States

Location

Metroplex Clinical Research Center

Dallas, Texas, 75231, United States

Location

Centre Hospitalier Régional Universitaire de Lille - Hôpital Claude Huriez

Lille, 59037, France

Location

Hopital Europeen Marseille

Marseille, 13003, France

Location

Hopital Pitie-Salpetriere

Paris, 75013, France

Location

Centre Hospitalier Universitaire de Strasbourg - Nouvel hopital civil

Strasbourg, 67091, France

Location

Charite Universitätsmedizin Berlin

Berlin, 10117, Germany

Location

Clinical Research Center Spzoo Medic-R Spolka Komandytowa

Poznan, 60-848, Poland

Location

Tomasz Blicharski Lubelskie Centrum Diagnostyczne

Świdnik, 21-040, Poland

Location

Medycyna Kliniczna Marzena Waszczak - Jeka

Warsaw, 00-874, Poland

Location

Wojewodzki Szpital Specjalistyczny we Wroclawiu

Wroclaw, 51-124, Poland

Location

Related Publications (1)

• Hannon CW, McCourt C, Lima HC, Chen S, Bennett C. Interventions for cutaneous disease in systemic lupus erythematosus. Cochrane Database Syst Rev. 2021 Mar 9;3(3):CD007478. doi: 10.1002/14651858.CD007478.pub2.

  PMID: 33687069 DERIVED

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

medinfo@amgen.com

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This phase 1b study is a double-blind, placebo controlled multiple ascending dose (MAD) study to evaluate the safety and tolerability of Efavaleukin Alfa in participants with systemic lupus erythematosus (SLE) and to determine the recommended phase 2 dose(s). Participants will be treated for a total of 12 weeks followed by a 6 week follow-up period. Five dosing cohorts are planned for the study.

Study Record Dates

• First Submitted: February 1, 2018
• First Posted: March 1, 2018
• Study Start: April 10, 2018
• Primary Completion: October 12, 2021
• Study Completion: October 12, 2021
• Last Updated: July 19, 2023
• Results First Posted: July 19, 2023

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• 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 (or other new use) 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.
• 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, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. 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 link below.

Locations

FR (4); PL (4); US (6); DE (1)