A Phase 3 Study of Obexelimab in Patients with IgG4-Related Disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Zenas Biopharma (USA) LLC

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

9 Jun 2023 → ongoing

Decision date (initial)

2023-04-18

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Zenas BioPharma (USA) LLC

External identifiers

EU CT number

2022-500718-24-00

WHO UTN

U1111-1281-5874

ClinicalTrials.gov

NCT05662241

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Others, Therapy, Safety, Efficacy

RCP: To evaluate the effect of weekly SC administration of obexelimab on IgG4-RD flare following an initial course of GC therapy in patients with active IgG4-RD

Secondary objectives 1

1. RCP: 1. To evaluate the effect of weekly SC administration of obexelimab on measures of disease activity in patients with IgG4-RD 2. To evaluate the safety and tolerability of weekly SC administration of obexelimab in patients with active IgG4-RD

Conditions and MedDRA coding

IgG4-Related Disease

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. RCP:1. Males and females, ≥ 18 years of age 2. Clinical diagnosis of IgG4-RD 3. Patients must meet the 2019 ACR/EULAR Classification Criteria for IgG4-RD with a score of ≥ 20 4. Patients must have active IgG4-RD signs/symptoms that require the initiation of GC therapy or the increase in background long-term GC therapy 5. A female patient not pregnant, not breastfeeding, and at least 1 of the following conditions applies: a. Not a woman of childbearing potential (WOCBP) OR b. A WOCBP who agrees to follow the contraceptive guidance until at least 8 weeks after the last IMP administration; c.Agree to refrain from egg donation throughout the study and until at least 8 weeks after the last dose of IMP 6. A male patient must: a. Agree to (i) abstain from intercourse or (ii) use contraception until at least 8 weeks after the last dose of IMP, or (iii) be surgically sterile for the duration of the study AND b. Agree to refrain from donating sperm until at least 8 weeks after the last dose of IMP 7. A WOCBP must have a negative serum pregnancy test at screening and a negative urine test prior to the first dose of IMP and at all timepoints specified in the protocol 8. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in the protocol 9. Willing to comply with all study protocol procedures and complete all study visits 10. Total duration of GC treatment prior to randomization must be ≥ 3 weeks and a maximum of 6 weeks at a dose of 20 to 60 mg/day OLE: 1.Have remained on study and completed the Week 52 RCP visit 2. Have not had IMP discontinued due to the following safety reasons: a. Grade ≥ 3 TEAE that is considered related to obexelimab b.Pregnancy; c. Malignancy; d. Hypersensitivity to IMP; e. Determination that the patient was ineligible for the RCP;f. For any reason deemed necessary by the investigator for patient safety 3. Have not discontinued from IMP due to unblinding of a patient 4. Have not received B-cell-depleting, B-cell-targeted, or other biologic immunomodulatory agents (apart from obexelimab) within the 6 months prior to enrollment in the OLE period. Patients who received B-cell-targeted therapy prior to enrollment in the OLE must have a B-cell count that is within the laboratory reference range, as measured by the central laboratory 5.For the rest of the inclusion criteria, please refer to the study protocol.

Exclusion criteria 1

1. RCP: 1. Any exclusion criteria listed in the ACR/EULAR Classification Criteria for IgG4-RD 2. Has disease in only 1 organ system whose primary manifestation is fibrosis (i.e., retroperitoneum fibrosis without aortitis, Riedel’s thyroiditis, fibrosing mediastinitis, sclerosing mesenteritis involvement, etc.) 3. Has received prednisone equivalent given orally at a dose greater than 60 mg/day within the 4 weeks prior to screening or during screening 4. Has received a non-biologic, disease-modifying anti-rheumatological drug or immunosuppressive agent other than GCs within the 2 weeks prior to screening 5. Has received an investigational treatment or direct medical intervention on another clinical study within 12 weeks or < 5 half-lives of the investigational treatment, whichever is shorter,prior to screening 6. Has received live vaccine or live therapeutic infectious agent within the 2 weeks prior to screening 7. Acute hepatitis B infection (hepatitis B surface antigen-positive), active hepatitis C virus, orHIV infection. Patients will be excluded from the RCP if they have a positive test for active hepatitis B through detection of (a) hepatitis B surface antigen or (b) hepatitis B core antibody. In Japan, patients will be excluded if there is detection of (a) hepatitis B surface antigen (b) hepatitis B surface antibody, or (c) hepatitis B core antibody. 8. Evidence of active tuberculosis (TB) or at high risk for TB as shown by at least one of the following: a. Documented history of active TB or latent TB, unless completion of treatment according to local guidelines; b. Positive, indeterminate, or invalid interferon-gamma release assay results at screening, unless treatment is documented. Patients with an indeterminate test result can repeat the test once either centrally or locally, but if the repeat test is also indeterminate, the patient is excluded; c. Signs of symptoms that could represent active TB; d. Chest radiograph, computed tomography (CT), or magnetic resonance imaging (MRI) that suggests possible diagnosis of TB 9. History or evidence of a clinically unstable/uncontrolled disorder, condition, or disease (including, but not limited to, cardiopulmonary, oncologic, renal, hepatic, metabolic, hematologic, psychiatric, active infection) other than IgG4-RD that, in the opinion of the investigator, would pose a risk to patient safety or interfere with the study evaluation, procedures, or completion 10. Malignancy within 5 years (except successfully treated in situ cervical cancer, resected squamous cell or basal cell carcinoma of the skin, breast cancer with no recurrence ≥ 5 years following therapy, or prostate cancer with no recurrence ≥ 3 years following prostatectomy) For the rest of the exclusion criteria, please refer to the study protocol.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. RCP: Time to first IgG4-RD flare, defined as the reappearance of previous signs/symptoms or appearance of new signs/symptoms of IgG4-RD that requires initiation of rescue therapy in the opinion of the investigator and the Adjudication Committee (AC), from randomization to Week 52

Secondary endpoints 5

1. RCP: Time to IgG4-RD flare that requires initiation of rescue therapy, as determined by the investigator
2. RCP: Number of investigator- and AC-determined flares requiring initiation of rescue therapy from randomization to Week 52
3. RCP: The proportion of patients achieving complete remission, defined as no AC-determined flare, no treatment for flare, and either an IgG4-RD Responder Index (RI) score of 0 or determination by the investigator that there was no clinical evidence of active disease at Week 52
4. RCP: Cumulative dose of IgG4-RD GC rescue therapy from randomization to Week 52
5. RCP: Incidence of adverse events (AEs), serious adverse events (SAEs), and any AEs of special interest (AESIs), as defined by the Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE v5.0)

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Zenas Biopharma (USA) LLC

Sponsor organisation

Zenas Biopharma (USA) LLC

Address

852 Winter Street Suite 250

City

Waltham

Postcode

02451-1439

Country

United States

Scientific contact point

Organisation

Zenas Biopharma (USA) LLC

Contact name

Allen Poma

Public contact point

Organisation

Zenas Biopharma (USA) LLC

Contact name

Allen Poma

Third parties 17

Locations

8 EU/EEA countries · 29 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 133 files

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

Application history

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