Inebilizumab efficacy and safety in IgG4 related disease

• Register: EUCTR
• Last refreshed on: 13 October 2020
• Main ID: EUCTR2020-000417-33-HU
• Date of registration: 06/08/2020
• Prospective Registration: Yes
• Primary sponsor: Viela Bio, Inc.
• Public title: Inebilizumab efficacy and safety in IgG4 related disease
• Scientific title: A Phase 3, Randomized, Double-blind, Multicenter, Placebo-Controlled Study of Inebilizumab Efficacy and Safety in IgG4 Related Disease - MITIGATE
• Date of first enrolment: 06/10/2020
• Target sample size: 200
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2020-000417-33
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: yes; Other trial design description: The second part of trial is optional and open label; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Canada, China, France, Germany, Hungary, India, Israel, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Poland, Spain, Ukraine, United Kingdom, United States

Contacts

• Name: Clinical Trials Information
• Affiliation: Viela Bio, Inc.

• Name: Clinical Trials Information
• Affiliation: Viela Bio, Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
.Male or female adults, = 18 years of age at time of informed consent.
.Written informed consent and any locally required authorization.
.Clinical diagnosis of IgG4-RD.
.Fulfillment of the 2019 ACR/EULAR classification criteria, as determined by the Eligibility Committee. Specifically, subjects must meet the classification criteria entry requirements (including involvement of one of the following organs: pancreas, bile ducts/biliary tree, orbits, lungs, kidneys, lacrimal glands, major salivary glands, retroperitoneum, aorta, pachymeninges, or thyroid gland [Riedel’s thyroiditis]), must not meet any of the classification criteria exclusions, and must achieve at least 20 classification criteria inclusion points.
.Experiencing (or recently experienced) an IgG4-RD flare that requires initiation or continuation of GC treatment at the time of informed consent. This criterion may be met in two ways: - On GC therapy for recent IgG4-RD flare, having received a maximum of 4 weeks of treatment prior to informed consent at a dose no higher than 60 mg/day prednisone or equivalent, and at 20 mg/day prednisone or equivalent on the day prior to randomization, or
- Experiencing active disease not currently being treated at the time of informed consent, with planned initiation of treatment for flare with GC at a maximum dose of 60 mg/day prednisone (or equivalent) and with a plan to be treated at a dose of 20 mg/day of prednisone (or equivalent) on the day prior to randomization, for a total duration of GC treatment during screening of at least 3 weeks at the time of randomization. This GC therapy can either be newly initiated or be increased from a maintenance dose of = 10 mg/day of prednisone or equivalent. Subjects unable to be tapered to 20 mg/day of prednisone or equivalent by Visit 2 may not be randomized.
.IgG4-RD affecting at least 2 organs/sites at any time in the course of IgG4-RD with documentation to confirm.
.Willing and able to comply with the protocol, complete study assessments, and complete the study period.
.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
Exclusion criteria:
.Severe cardiovascular, respiratory, endocrine, gastrointestinal, hematological, neurological, psychiatric, or systemic disorder, or any other condition that, in the opinion of the Investigator, would place the patient at unacceptable risk of complications, interfere with evaluation of the IP, or confound the interpretation of patient safety or study results.
.History of solid organ or cell-based transplantation.
.Known immunodeficiency disorder.
.Active malignancy or history of malignancy that was active within the last 10 years.
.Receipt of any biologic B cell-depleting therapy in the 6 months prior to screening. Receipt of such a B cell-depleting agent in the period 6-12 months prior to screening is exclusionary unless B cell counts have returned to = LLN by central laboratory.
.Receipt of non-depleting B-cell-directed therapy, abatacept, or other biologic immunomodulatory agent within 6 months prior screening.
.Receipt of non-biologic DMARD or immunosuppressive agent other than GCs within 4 weeks prior to screening.
.Receipt of any investigational agent < 12 weeks or < 5 half-lives of the drug prior to screening.
.Inability to be tapered off of GC therapy by 8 weeks post-randomization, in the opinion of the Investigator.
.Receipt of live vaccine or live therapeutic infectious agent within the 2 weeks prior to screening.
.Pregnancy, lactation, or planning to become pregnant within 6 months of the last dose of IP.
.Positive test for, or prior treatment for, hepatitis B or HIV infection. A positive test for hepatitis B is detection of either (1) hepatitis B surface antigen (HBsAg); or (2) hepatitis B core antibody (anti-HBc).
.History of untreated hepatitis C infection, or positive antibody test for hepatitis C virus (HCV) unless patient is considered to be cured following antiviral therapy and has a HCV load below the limit of detection at least 24 weeks after completion of treatment.
.Evidence of active tuberculosis (TB) or being at high risk for TB based on: - History of active TB or untreated/incompletely treated latent TB. Patients with a history of active or latent TB who have documentation of completion of treatment according to local guidelines may be enrolled.
.History of > 1 episode of herpes zoster and/or any other definite or probable opportunistic infection in the 12 months prior to screening.
.Known history of allergy or reaction to any component of inebilizumab formulation or history of anaphylaxis to any human gamma globulin therapy.
.Allergy to or intolerance of protocol-required treatment, including medications for prophylaxis of infusion reactions.
.Estimated glomerular filtration rate < 30 mL/min/1.73 m2 by Modification of Diet in Renal Disease Study (MDRD) equation (NIDDK).
.Blood tests at screening that meet any of the following criteria: - Hemoglobin < 7.5 g/dL
- Neutrophils < 1200/mm3
- Platelets < 110 × 109/L
- Eosinophil count > 3000/mm3
- Prothrombin time above upper limit of normal (ULN)
.Subjects with the following abnormal liver function tests in the absence of hepatobiliary IgG4-RD activity: - Aspartate aminotransferase (AST) > 2 × ULN
- Alanine aminotransferase (ALT) > 2 × ULN
- Total bilirubin (TBL) > 2 × ULN unless AST, ALT, and hemoglobin are within central laboratory normal range and the patient has a known history of Gilbert syndrome
OR
Subjects with the following abnormal liver function tests in the presence of hepatobiliary IgG4-RD activity:
- AST > 10 × ULN
- ALT > 10 ×

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Immunoglobulin G4-related disease (IgG4-RD)
MedDRA version: 20.0 Level: PT Classification code 10077271 Term: Immunoglobulin G4 related disease System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

Product Name: Inebilizumab
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: INEBILIZUMAB
Current Sponsor code: MEDI-551
Other descriptive name: afucosylated IgG1 kappa monoclonal antibody
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Concentrate for solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Main Objective: To evaluate the efficacy of inebilizumab in reducing the risk of a disease flare in patients with IgG4-RD

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.

Secondary Objective: .To evaluate the safety and tolerability of inebilizumab in patients with IgG4-RD.
.To evaluate the effect of inebilizumab on other measures of disease activity

Timepoint(s) of evaluation of this end point: 52-week RCP

Secondary Outcome(s)

Secondary end point(s): .Incidence of TEAEs, TESAEs, and treatment-emergent adverse events of special interest (AESIs) during the 52-week RCP and during the OLP.
.The incidence of ADAs directed against inebilizumab during the RCP.
.Annualized flare rate for treated and AC-determined flares during the RCP.
.Annualized flare rate for AC-determined flares, whether or not treated, during the RCP.
.The proportion of subjects achieving flare-free complete remission at Week 52. Complete remission is defined as an IgG4-RD Responder Index (RI, Wallace et al, 2018) score of 0 at Week 52, no AC-determined flare during the RCP, and no treatment for flare or disease control except the required 8-week GC taper.
.Time to initiation of first treatment (medication or procedure) for new or worsening disease activity by the Investigator within the RCP, regardless of AC determination of flare.
.Glucocorticoid use, calculated as the cumulative GC dose taken for the purpose of IgG4-RD disease control during the RCP.

Timepoint(s) of evaluation of this end point: 52-week RCP

Secondary ID(s)

2020-000417-33-DE

VIB0551.P3.S2

Source(s) of Monetary Support

Viela Bio, Inc.

Ethics review

Status: Approved
Approval date: 15/09/2020
Contact: