Study to Evaluate the Pharmacokinetics, Safety and Tolerability of Intravenous Secukinumab in Patients With GCA or PMR

NCT06130540 | Completed Phase 1 FDA Drug

• 2 other identifiers: CAIN457E221012023-507667-19-00
• Study Type: interventional
• Target: 65
• Locations: 6 countries
• Sites: 19

Brief Summary

This study will examine how intravenous (i.v.) Secukinumab will be processed in the body (pharmacokinetics \[PK\]) and whether it will be safe and tolerable after multiple doses of i.v. Secukinumab infusion in adult patients with giant cell arteritis (GCA) or polymyalgia rheumatica (PMR).

Conditions

Giant Cell Arteritis; Polymyalgia Rheumatica

Keywords

Giant cell arteritis (GCA); Polymyalgia rheumatica (PMR); Secukinumab; pharmacokinetics; intravenous

Outcome Measures

Primary Outcomes (4)

• Secukinumab: Maximum concentration at steady state (Cmax,ss)

  Venous whole blood samples will be collected and analyzed for all PK evaluable participants. Maximum concentration at steady state (Cmax,ss) will be listed and summarized using descriptive statistics.

  Baseline, Week 4 and Week 8: Pre-dose and End-of Infusion (EOI); Weeks 9, 10, 11, 12, 16 and 20: Anytime

• Secukinumab: Minimum concentration at steady state (Cmin,ss)

  Venous whole blood samples will be collected and analyzed for all PK evaluable participants. Minimum concentration at steady state (Cmin,ss) will be listed and summarized using descriptive statistics.

  Baseline, Week 4 and Week 8: Pre-dose and End-of Infusion (EOI); Weeks 9, 10, 11, 12, 16 and 20: Anytime

• Secukinumab: Area under the concentration-time curve at steady state during a dosing interval (AUCtau,ss)

  Venous whole blood samples will be collected and analyzed for all PK evaluable participants. Area under the concentration-time curve at steady state during a dosing interval (AUCtau,ss) will be listed and summarized using descriptive statistics.

  Baseline, Week 4 and Week 8: Pre-dose and End-of Infusion (EOI); Weeks 9, 10, 11, 12, 16 and 20: Anytime

• Secukinumab: Average concentration at steady state (Cavg,ss [=AUCtau,ss/tau])

  Venous whole blood samples will be collected and analyzed for all PK evaluable participants. Average concentration at steady state (Cavg,ss \[=AUCtau,ss/tau\]) will be listed and summarized using descriptive statistics.

  Baseline, Week 4 and Week 8: Pre-dose and End-of Infusion (EOI); Weeks 9, 10, 11, 12, 16 and 20: Anytime

Secondary Outcomes (3)

• Number of Participants with Treatment Emergent Adverse Events

  Up to 12 weeks after last dose administration.

• Secukinumab: Clearance (CL)

  Baseline, Week 4 and Week 8: Pre-dose and End-of Infusion (EOI); Weeks 9, 10, 11, 12, 16 and 20: Anytime

• Secukinumab: Volume of distribution at steady state (Vss)

  Baseline, Week 4 and Week 8: Pre-dose and End-of Infusion (EOI); Weeks 9, 10, 11, 12, 16 and 20: Anytime

Study Arms (2)

Secukinumab: Giant Cell Arteritis (GCA)

EXPERIMENTAL

Drug: Secukinumab

Secukinumab: Polymyalgia Rheumatica (PMR)

EXPERIMENTAL

Drug: Secukinumab

Interventions

Secukinumab DRUG

Intravenous (i.v.) doses of Secukinumab at Week 0, Week 4 and Week 8

Also known as: AIN457

Secukinumab: Giant Cell Arteritis (GCA); Secukinumab: Polymyalgia Rheumatica (PMR)

Eligibility Criteria

• Age: 50 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or non-pregnant, non-lactating female participants at least 50 years of age
• Diagnosis of GCA based on meeting all of the following criteria:
• Unequivocal cranial symptoms of GCA (e.g., new-onset localized headache, scalp or temporal artery tenderness, permanent or temporary ischemia-related vision loss, or otherwise unexplained mouth or jaw pain upon mastication), and/or unequivocal symptoms of PMR (defined as shoulder and/or hip girdle pain associated with inflammatory morning stiffness) and/or symptoms of limb ischemia (claudication)
• Temporal artery biopsy (TAB) revealing features of GCA and/or cross-sectional imaging study such as ultrasound (e.g., cranial or axillary), MRI/MRA, CTA, or PET-CT with evidence of vasculitis
• Active GCA disease within 6 months prior to Baseline as defined by meeting both of the following:
• Presence of signs or symptoms attributed to active GCA and not related to prior damage (e.g., vision loss that occurred without new findings)
• Elevated ESR \>= 30 mm/hr or CRP \>= 10 mg/L attributed to active GCA or active GCA on TAB or on imaging study
• Male or non-pregnant, non-lactating female participants at least 50 years of age
• Diagnosis of PMR according to the provisional ACR/EULAR classification criteria: Participants \>= 50 years of age with a history of bilateral shoulder pain accompanied by elevated CRP concentration (\>= 10 mg/L) and/or elevated ESR (\>= 30 mm/hr) who scored at least 4 points from the following optional classification criteria:
• Morning stiffness \>45 min (2 points)
• Hip pain or restricted range of motion (1 point)
• Absence of rheumatoid factor and/or anti-citrullinated protein antibodies (2 points)
• Absence of other joint involvement (1 point)
• Active PMR disease within 6 months prior to Baseline as defined by signs and symptoms attributable to PMR meeting the following:
• Bilateral shoulder girdle and/or bilateral hip girdle pain associated with inflammatory stiffness with or without additional symptoms indicative of a PMR relapse (such as constitutional symptoms) that are in the opinion of the Investigator not due to other diseases that may mimic PMR such as osteoarthritis in shoulders or hips, polyarticular calcium pyrophosphate deposition disease, rotator cuff disease, adhesive capsulitis (frozen shoulder) or fibromyalgia

You may not qualify if:

• Pregnant or nursing (lactating) women where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test
• History of hypersensitivity or contraindication to any of the study treatments or its excipients or to drugs of similar chemical classes
• Use of other investigational drugs within 5 half-lives of enrollment or within 30 days (e.g., small molecules) or until the expected pharmacodynamic effect has returned to BSL (e.g., biologics), whichever is longer; or longer if required by local regulations
• History of clinically significant liver disease or liver injury as indicated by clinically significantly abnormal liver function tests (LFTs), such as SGOT (AST), SGPT (ALT) and serum bilirubin. The Investigator should be guided by the following criteria:
• AST (Aspartate Aminotransferase) and ALT (Alanine Aminotransferase) may not exceed 3 x the upper limit of normal (ULN)
• Total bilirubin concentration may not exceed 1.5 x ULN Any one of these parameters, if elevated above ULN, should be re-checked once more as soon as possible, and in all cases, at least prior to enrollment, to rule-out laboratory error.
• Active infections or history of ongoing, chronic or recurrent infectious disease including but not limited to below:
• Active infections during the last 2 weeks prior to BSL
• Known infection with human immunodeficiency virus (HIV), hepatitis B (HBV) or hepatitis C (HCV) at screening or BSL, except for HCV successfully treated and cured, according to local/global guidelines
• Evidence of tuberculosis (TB) infection as defined by a positive QuantiFERON TB-Gold Plus test. Participants with a positive test may participate in the study if further work-up (according to local practice/guidelines) establishes conclusively that the participant has no evidence of active TB. If the test result is indeterminate, the Investigator may repeat the test once or may proceed directly to perform the work-up for TB as per local procedures. If presence of latent TB is established, then treatment must be initiated prior to BSL (both treatment and timing prior to BSL according to local country guidelines)
• Active inflammatory bowel disease or active uveitis
• Active ongoing diseases which in the opinion of the Investigator immuno-compromises the participant and/or places the participant at unacceptable risk for treatment with immunomodulatory therapy
• Current severe progressive or uncontrolled disease, which in the judgment of the Investigator renders the participant unsuitable for the trial, including but not limited to below:
• Major ischemic event (e.g., myocardial infarction, stroke, etc.) or transient ischemic attack (TIA) within 12 weeks of screening
• Significant medical conditions or diseases, including but not limited to the following: uncontrolled hypertension, congestive heart failure (New York Heart Association (NYHA) status of class III or IV) and uncontrolled diabetes mellitus

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (19)

Rheumatology Associates of South Florida

Boca Raton, Florida, 33486, United States

Location

FL Medical Clinic Orlando Health

Zephyrhills, Florida, 33542, United States

Location

Willow Rheumatology Wellness

Willowbrook, Illinois, 60527, United States

Location

Altoona Center for Clin Res

Duncansville, Pennsylvania, 16635, United States

Location

West Tennessee Research Institute

Jackson, Tennessee, 38305, United States

Location

Accurate Clinical Research Inc

San Antonio, Texas, 78229, United States

Location

Overlake Internal Med Associates

Bellevue, Washington, 98004, United States

Location

Rheumatology Pulmonary Clinic

Beckley, West Virginia, 25801, United States

Location

Novartis Investigative Site

Uherské Hradiště, Uherske Hradiste, 686 01, Czechia

Location

Novartis Investigative Site

Brno-Bohunice, 625 00, Czechia

Location

Novartis Investigative Site

Florence, FI, 50134, Italy

Location

Novartis Investigative Site

Reggio Emilia, RE, 42123, Italy

Location

Novartis Investigative Site

Lisbon, 1649 035, Portugal

Location

Novartis Investigative Site

Santiago de Compostela, Galicia, 15706, Spain

Location

Novartis Investigative Site

Madrid, 28009, Spain

Location

Novartis Investigative Site

Madrid, 28046, Spain

Location

Novartis Investigative Site

Basel, 4031, Switzerland

Location

Novartis Investigative Site

Bern, 3010, Switzerland

Location

Novartis Investigative Site

Sankt Gallen, 9007, Switzerland

Location

Related Links

• CAIN457E22101 Clinical Trial Results
• A Plain Language Trial Summary is available on www.novctrd.com

MeSH Terms

Conditions

Giant Cell Arteritis; Polymyalgia Rheumatica

Interventions

secukinumab

Condition Hierarchy (Ancestors)

Vasculitis, Central Nervous System; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Arteritis; Vasculitis; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Muscular Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 30 patients per cohort (Giant Cell Arteritis (GCA) and Polymyalgia Rheumatica (PRM) are planned to be enrolled

Study Record Dates

• First Submitted: November 8, 2023
• First Posted: November 14, 2023
• Study Start: March 27, 2024
• Primary Completion: March 12, 2025
• Study Completion: April 2, 2025
• Last Updated: April 1, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (2); ES (3); CH (3); US (8); PT (1); CZ (2)