A Study of Inebilizumab Efficacy and Safety in IgG4- Related Disease

Phase 3Active Not RecruitingNCT04540497

Amgen135 enrolled

Overview

This study aims to evaluate the efficacy and safety of inebilizumab for the prevention of flare of Immunoglobulin G4-related disease (IgG4-RD).

After a screening period of up to 28 days, subjects with IgG4-RD at high risk of flare due to multi-organ disease and recent active disease will be randomized in a 1:1 ratio to receive intravenous (IV) inebilizumab or placebo after premedication during the 52-week randomized control period (RCP). All subjects will receive an initial tapering dose of glucocorticoids (GCs) to complete treatment of their active disease. Flares occurring during study will be treated. The primary endpoint is time to a first adjudication committee-determined, investigator-treated disease flare during the RCP. The primary analysis will be conducted when the last subject completes the RCP visit or discontinues the RCP. This study includes an optional 3-year open-label treatment period. The study also includes a Safety Follow-up Period (SFUP) of up to 730 days for all participants. The expected duration of each subject's participation in this study is up to 400 days (screening and RCP), plus up to 1095 days for eligible subjects who enroll in the optional open label period (OLP), and up to 730 days for the SFUP, for a total maximum duration of up to 2273 days (screening, RCP, interval between RCP and OLP, OLP, and FSUP). Study acquired from Horizon in 2024.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

135

Conditions

IgG4 Related Disease

Interventions

InebilizumabDRUG

Inebilizumab is a monoclonal antibody that depletes B cells.

PlaceboOTHER

Placebo

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: 1. Male or female adults, ≥ 18 years of age at time of informed consent. 2. Clinical diagnosis of IgG4-RD. 3. Fulfillment of the 2019 ACR/EULAR classification criteria. 4. Experiencing (or recently experienced) an IgG4-RD flare that requires initiation or continuation of glucocorticoid (GC) treatment at the time of informed consent. 5. IgG4-RD affecting at least 2 organs/sites at any time in the course of IgG4-RD 6. Non-sterilized male subjects who are sexually active with a female partner of childbearing potential must use a condom with spermicide from Day 1 through to the end of the study and must agree to continue using such precautions for at least 6 months after the final dose of IP. Females of childbearing potential who are sexually active with a non-sterilized male partner must use a highly effective method of contraception Key Exclusion Criteria: 1. History of solid organ or cell-based transplantation or known immunodeficiency disorder. 2. Active malignancy or history of malignancy that was active within the last 10 years (some specific situations for cervical, skin or prostate cancer are acceptable). 3. Receipt of any biologic B cell-depleting therapy or non-depleting B-cell-directed therapy in the 6 months prior to screening. 4. Receipt of non-biologic DMARD or immunosuppressive agent other than GCs within 4 weeks prior to screening. 5. Active tuberculosis or high risk for tuberculosis; hepatitis C infection in absence of curative treatment; evidence of hepatitis B infection. 6. Receipt of live vaccine or live therapeutic infectious agent within 2 weeks prior to screening. 7. Estimated glomerular filtration rate \< 30 mL/min/1.73 m\^2.

Locations (72)

Outcomes

Primary Outcomes

RCP: Time to Disease Flare

Time to disease flare was defined as the number of days from Day 1 (dosing) to the date of the first treated and Adjudication Committee (AC)-determined IgG4-RD flare within the 52-week RCP. The date of disease flare was determined by the initiation of any flare treatment, including new or increased glucocorticoid (GC) treatment, other immunotherapy, or an interventional procedure, as deemed necessary by the Investigator to address the flare. Kaplan-Meier (KM) method was used to estimate the median time to flare, and 95% confidence interval (CI).

Time frame: Up to Week 52

Secondary Outcomes

RCP: Annualized Rate of Treated and AC-Determined Flares During the RCP

The annualized rate of treated and AC-determined flares during the 52-week RCP was calculated by dividing the total number of treated and AC-determined flares by the total time at risk (in years) for all participants. This measure reflected the frequency of disease flares per person per year during the RCP.

Time frame: Week 52

RCP: Percentage of Participants Achieving Flare-free, Treatment-free Complete Remission at Week 52

Flare-free, treatment-free complete remission at Week 52 was defined as the absence of evident disease activity at Week 52, no AC-determined flare during the RCP, and no treatment for flare or disease control, except for the required 8-week glucocorticoid taper. Lack of evident disease activity was determined by either a score of 0 on the IgG4-RD Responder Index (score range: 0-4, with lower scores indicating better disease control) or an investigator's assessment that no disease activity was present based on physical, laboratory, pathology, or other evidence.

Time frame: Week 52

RCP: Percentage of Participants Achieving Flare-free, Corticosteroid-free Complete Remission at Week 52

Flare-free, corticosteroid-free complete remission at Week 52 was defined as the absence of evident disease activity at Week 52, no AC-determined flare during the RCP, and no corticosteroid treatment for flare or disease control, except for the required 8-week glucocorticoid taper. Lack of evident disease activity was determined by either a score of 0 on the IgG4-RD Responder Index (score range: 0-4, with lower scores indicating better disease control) or an investigator's assessment that no disease activity was present based on physical, laboratory, pathology, or other evidence.

Data from ClinicalTrials.gov

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Viela Bio Investigative Site

Palo Alto, California, United States

Viela Bio Investigative Site

Atlanta, Georgia, United States

Viela Bio Investigative Site

Baltimore, Maryland, United States

Viela Bio Investigative Site

Boston, Massachusetts, United States

Viela Bio Investigative Site

Buenos Aires, Argentina

Viela Bio Investigative Site

Mendoza, Argentina

Viela Bio Investigative Site

Auchenflower, Queensland, Australia

Viela Bio Investigative Site

Adelaide, South Australia, Australia

Viela Bio Investigative Site

Fitzroy, Australia

Viela Bio Investigative Site

Sherbrooke, Canada

...and 62 more locations

Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) During the RCP

An adverse event (AE) referred to any untoward medical occurrence in a clinical study participant, regardless of a causal relationship with the study treatment. TEAEs included any event occurring after the participant received the study treatment. Clinically significant changes in vital signs, electrocardiograms, and laboratory tests recorded after treatment administration were documented as TEAEs. Serious AEs (SAEs) were untoward medical occurrences after the first dose, irrespective of a causal link to the study treatment, that led to death, were life-threatening, required hospitalization or its prolongation, caused significant disability, resulted in congenital anomalies, or were considered other medically important events. AEs were graded (Grade 3: severe; Grade 4: life-threatening; Grade 5: death) using the Common Terminology Criteria for Adverse Events \[CTCAE\]).

Time frame: Up to Week 52

Number of Participants Who Experienced TEAEs During the OLP

An AE referred to any untoward medical occurrence in a clinical study participant, regardless of a causal relationship with the study treatment. TEAEs included any event occurring after the participant received the study treatment. Clinically significant changes in vital signs, electrocardiograms, and laboratory tests recorded after treatment administration were documented as TEAEs. SAEs were untoward medical occurrences after the first dose, irrespective of a causal link to the study treatment, that led to death, were life-threatening, required hospitalization or its prolongation, caused significant disability, resulted in congenital anomalies, or were considered other medically important events. AEs were graded (Grade 3: severe; Grade 4: life-threatening; Grade 5: death) using the CTCAE).

Time frame: From the first dose of investigational product in OLP to the end of OLP or cutoff date; median (min, max) duration was 51.6 (0.1, 108.3) weeks.

RCP: Number of Participants With Anti-drug Antibodies (ADA) to Inebilizumab by Week 52

Incidence was the proportion of the participants with ADA positive post-baseline only or boosted their preexisting ADA (at least 4-fold over the baseline titer) during the study period. Baseline was defined as the last valid value on or before the first dose of RCP.

Time frame: Baseline to Week 52

RCP: Time to Initiation of First Treatment for New or Worsening Disease Activity Within the RCP

Time to initiation of the first treatment (medication or procedure) for new or worsening disease activity, as determined by the investigator, within the RCP, was measured from day 1 (dosing) to the date the first treatment was administered. It Included any treatment initiated by the investigator for disease activity, regardless of the AC determination of flare. KM method was used to estimate the median time to the initiation of first treatment or worsening of disease activity, and 95% CI.

Time frame: Week 52

RCP: Annualized Flare Rate for AC-Determined IgG4-RD Flares at Week 52

The annualized flare rate for AC-determined IgG4-RD flares, whether or not treated, during the RCP was calculated by dividing the total number of AC-determined flares by the total time at risk (in years) for all participants. This measure reflected the frequency of IgG4-RD flares, irrespective of treatment, per participant per year during the study period.

Time frame: Week 52

RCP: Cumulative Glucocorticoid (GC) Use for IgG4-RD Disease Control by Week 52

GC use was calculated as the cumulative glucocorticoid dose (in milligrams) taken for the purpose of IgG4-RD disease control during the RCP. This measure accounted for all GC treatments administered to participants to manage disease activity throughout the study period.

Time frame: Week 52