Inebilizumab efficacy and safety in IgG4 related disease

Phase 1

• Conditions: Immunoglobulin G4-related disease (IgG4-RD); MedDRA version: 20.0Level: PTClassification code 10077271Term: Immunoglobulin G4 related diseaseSystem Organ Class: 10028395 - Musculoskeletal and connective tissue disorders; Therapeutic area: Diseases [C] - Immune System Diseases [C20]

• Registration Number: EUCTR2020-000417-33-IT
• Lead Sponsor: VIELABIO Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-10-21
• Last Update Posted: 26 July 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

1.Male or female adults, = 18 years of age at time of informed consent.
2.Written informed consent and any locally required authorization
3.Clinical diagnosis of IgG4-RD.
4.Fulfillment of the 2019 ACR/EULAR classification criteria as determined by the Eligibility Committee.
5.Experiencing (or recently experienced) an IgG4-RD flare that requires initiation or continuation of GC treatment at the time of informed consent
6.IgG4-RD affecting at least 2 organs/sites at any time in the course of IgG4-RD with documentation to confirm.
7.Willing and able to comply with the protocol, complete study assessments, and complete the study period.
8.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 must have a negative serum pregnancy test at screening. Females of childbearing potential who are sexually active with a non-sterilized male partner must use a highly effective method of contraception from signing informed consent and must agree to continue using such precautions through the end of the follow-up of the study and at least 180 days after the last dose of IP; cessation of contraception after this point should be discussed with a responsible physician. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception. A recommendation will be made that the female partners (of childbearing potential) of male study participants should use a highly effective method of contraception other than a barrier method.
Females of childbearing potential are defined as those who are not surgically sterile (ie, surgical sterilization includes bilateral tubal ligation, bilateral oophorectomy, or hysterectomy) or those who are not postmenopausal (defined as 12 months with no menses without an alternative medical cause and a follicle-stimulating hormone within the postmenopausal range as established by the clinical laboratory).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 160
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 40

Exclusion Criteria

1.Severe cardiovascular, respiratory, endocrine, gastrointestinal, hematological, neurological, psychiatric
2.History of solid organ or cell-based transplantation.
3.Known immunodeficiency disorder.
4.Active malignancy or history of malignancy that was active within the last 10 years, with exceptions (please see the protocol)
5.Receipt of any biologic B cell-depleting therapy in the 6 months prior to screening.

6.Receipt of non-depleting B-cell-directed therapy (eg, belimumab), abatacept, or other biologic immunomodulatory agent within 6 months prior screening.
7.Receipt of non-biologic DMARD or immunosuppressive agent other than GCs (eg, azathioprine, mycophenolate mofetil, methotrexate, others) within 4 weeks prior to screening.
8.Receipt of any investigational agent < 12 weeks or < 5 half-lives of the drug (whichever is longer) prior to screening.
9.Inability to be tapered off of GC therapy by 8 weeks post-randomization, in the opinion of the Investigator.
10.Receipt of live vaccine or live therapeutic infectious agent within the 2 weeks prior to screening.
11.Pregnancy, lactation, or planning to become pregnant within 6 months of the last dose of IP.
12.Positive test for, or prior treatment for, hepatitis B or HIV infection.
13.History of untreated hepatitis C infection, or positive antibody test for hepatitis C virus (HCV)
14.Evidence of active tuberculosis (TB) or being at high risk for TB
15.History of > 1 episode of herpes zoster (any grade) and/or any other definite or probable opportunistic infection in the 12 months prior to screening
16.Known history of allergy or reaction to any component of inebilizumab formulation or history of anaphylaxis to any human gamma globulin therapy.
17.Allergy to or intolerance of protocol-required treatment, including medications for prophylaxis of infusion reactions
18.Estimated glomerular filtration rate < 30 mL/min/1.73 m2 by Modification of Diet in Renal Disease Study (MDRD) equation (NIDDK).
19.Blood tests at screening that meet any of the criteria reported in the protocol
20.Subjects with the abnormal liver function tests in the absence of hepatobiliary IgG4-RD activity:
OR
Subjects with the abnormal liver function tests in the presence of hepatobiliary IgG4-RD activity:
21.Anti-neutrophil cytoplasmic antibodies (ANCA) targeted against proteinase 3 or myeloperoxidase at the central laboratory.
22.History of alcohol or drug abuse that, in the opinion of the Investigator, might affect patient safety or compliance with visits or interfere with safety or other study assessments.
23.Active, clinically significant infection at the time of randomization (IP administration may be delayed until recovery, if within screening window, otherwise subject may be rescreened).
24.Participation in any clinical trial that includes use of any pharmacologic intervention.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the efficacy of inebilizumab in reducing the risk of a disease flare in patients with IgG4-RD;Secondary Objective: • To evaluate the safety and tolerability of inebilizumab in patients with IgG4-RD.<br>.• To evaluate the effect of inebilizumab on other measures of disease activity;Primary end point(s): Time to disease flare, defined as the time in days from Day 1 (dosing) to the date of the first treated and AC-determined IgG4 RD flare within the 52-week RCP. The date of disease flare is defined as the date of initiation of any flare treatment (new or increased GC treatment, other immunotherapy, or interventional procedure) deemed necessary by the Investigator for the flare.;Timepoint(s) of evaluation of this end point: 52-week RCP