A Phase 3, Randomized, Double-Blind, Multicenter, Placebo-Controlled Study of Inebilizumab Efficacy and Safety in IgG4-Related Disease.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Horizon Therapeutics Ireland Designated Activity Company

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

18 Dec 2020 → ongoing

Decision date (initial)

2024-03-28

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Horizon Therapeutics Ireland DAC, Ireland

External identifiers

EU CT number

2023-508290-81-00

EudraCT number

2020-000417-33

ClinicalTrials.gov

NCT04540497

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacodynamic, Pharmacokinetic, Therapy, Efficacy

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

Secondary objectives 2

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

Conditions and MedDRA coding

Immunoglobulin G4-related disease (IgG4-RD)

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. 1.Male or female adults who have reached the age of consent in the applicable region (eg, ≥18 years in the US)
2. 2. Clinical diagnosis of IgG4-RD.
3. 3. Fulfillment of the 2019 ACR/EULAR classification criteria.
4. 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. 5. IgG4-RD affecting at least 2 organs/sites at any time in the course of IgG4-RD. One organ must meet the requirements for the ACR/EULAR classification criteria; the second organ is as defined by the investigator
6. 6. Non-sterilized male subjects who are sexually active with a female partner of childbearing potential must use a condom with spermicide (where spermicide is available) 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 highlyeffective method of contraception.

Exclusion criteria 7

1. 1. History of solid organ or cell-based transplantation or known immunodeficiency disorder .
2. 2. Active malignancy or history of malignancy that was active within the last 10 years (some specific situations for cervical, skin, prostate or thyroid cancer are acceptable).
3. 3. Receipt of any biologic B cell-depleting therapy or non-depleting Bcell- directed therapy in prior 6 months.
4. 4. Receipt of non-biologic DMARD or immunosuppressive agent other than GCs within prior 4 weeks
5. 5. Active tuberculosis or high risk for tuberculosis; hepatitis C infection in absence of curative treatment; evidence of hepatitis B infection
6. 6. Live vaccine or therapeutic agent in prior 2 weeks
7. 7. Glomerular filtration rate < 30 mL/min/1.73 m2

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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 endpoints 8

1. 1. Annualized flare rate for treated and AC-determined flares during the RCP.
2. 2. The proportion of subjects achieving flare-free, treatment-free complete remission at Week 52, defined as the lack of evident disease activity 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.
3. 3. The proportion of subjects achieving flare-free, corticosteroid-free complete remission at Week 52, defined as the lack of evident disease activity at Week 52, no AC-determined flare during the RCP, and no corticosteroid treatment for flare or disease control except the required 8-week GC taper.
4. 4. 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.
5. 5. Annualized flare rate for AC-determined flares, whether or not treated, during the RCP.
6. 6. Glucocorticoid use, calculated as the cumulative GC dose taken for the purpose of IgG4 RD disease control during the RCP.
7. 7. Incidence of treatment emergent adverse events (TEAEs), serious TESAEs, and TEAEs of special interest (AESIs) during the 52-week RCP and during the OLP.
8. 8. The incidence of ADAs directed against inebilizumab during the RCP.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Horizon Therapeutics Ireland Designated Activity Company

Sponsor organisation

Horizon Therapeutics Ireland Designated Activity Company

Address

Pottery Road, Dun Laoghaire Dun Laoghaire

City

Dublin

Postcode

A96 F2A8

Country

Ireland

Scientific contact point

Organisation

Horizon Therapeutics Ireland Designated Activity Company

Contact name

Sue Cheng

Public contact point

Organisation

Horizon Therapeutics Ireland Designated Activity Company

Contact name

Medical Information

Third parties 10

Locations

6 EU/EEA countries · 15 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 58 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

11 submissions — initial application plus substantial / non-substantial modifications