A study to evaluate efficacy and safety of obexelimab in patients with IgG4-related disease
| ISRCTN | ISRCTN18188034 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN18188034 |
| EudraCT/CTIS number | 2022-500718-24 |
| IRAS number | 1006349 |
| ClinicalTrials.gov number | NCT05662241 |
| Secondary identifying numbers | ZB012-03-001, IRAS 1006349, CPMS 54695 |
- Submission date
- 23/12/2022
- Registration date
- 02/04/2024
- Last edited
- 02/05/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Ongoing
- Condition category
- Haematological Disorders
Plain English summary of protocol
Background and study aims
IgG4-Related Disease (IgG4-RD) is a rare condition that causes inflammation and scarring in many different areas of the body, including the pancreas, biliary tract, salivary glands and other organs. IgG4-RD can cause different symptoms and affect one or multiple organs. Most patients are middle-aged to elderly men.
The current therapy for IgG4-RD consists of steroids followed by gradual withdrawal. This is initially effective, but 30 to 60% of patients will relapse after discontinued treatment. Long-term steroid therapy can cause several complications. Therefore, there is a need for novel treatment of IgG4-RD.
The purpose of this study is to evaluate the safety and effectiveness of obexelimab, on IgG4-RD. Obexelimab (a B cell targeted therapy) is an investigational drug, which means it has not yet been approved for the treatment of a disease by any regulatory agencies and can only be tested in a study like this one. There have been five studies of obexelimab with a total of 198 healthy volunteers or patients. A Phase 2 study in 20 participants with IgG4-RD showed strong and rapid improvement in their disease activity.
Who can participate?
Adults aged 18 years and older with a diagnosis of IgG4-RD who are experiencing active signs/symptoms of IgG4-RD
What does the study involve?
Approximately 200 adult participants are expected to take part globally. After an initial course of steroids, participants will enter a placebo-controlled period (a placebo is an inactive substance which resembles the study drug but has no medical value) where participants will receive obexelimab or placebo as a subcutaneous injection weekly for 52 weeks. At the end of the 52 weeks, participants may enter an open-label extension period, where all participants are given obexelimab for another 52 weeks. All participants will attend a follow-up visit when they complete the study. Study procedures include but are not limited to physical examination, vital signs, CT or MRI scan, blood samples, stool samples, quality of life questionnaires, glucocorticoid treatment and taper.
What are the possible benefits and risks of participating?
Taking part in this study may or may not help to treat your IgG4-RD. Your health could improve, stay the same, or get worse. However, the data we get from you during this study may help doctors learn more about the study drug and whether or not it provides any benefit to patients with IgG4-RD, and this may help future patients with IgG4-RD.
The safety of obexelimab has been studied in 198 people of whom 40 received the subcutaneous injection form used in this study. When obexelimab was given in the intravenous form, there was a serious but uncommon risk for allergic reactions and gastrointestinal symptoms like nausea, vomiting and diarrhea during infusion. Obexelimab treats IgG4-RD by changing your immune system which may cause you risk for infections. When obexelimab was given as the subcutaneous form, there were mild to moderate side effects at the site of injection including redness, pain, and swelling.
Where is the study run from?
Zenas BioPharma (USA) LLC
When is the study starting and how long is it expected to run for?
January 2022 to December 2026
Who is funding the study?
Zenas BioPharma LLC (USA)
Who is the main contact?
Dr Emma Culver, emma.culver@nhs.net
Contact information
Scientific
1-2 Crown Walk
Jewry Street
Winchester
SO23 8BB
United Kingdom
| Phone | +44 196 2896764 |
|---|---|
| UKStart-upteam.SM@ppd.com |
Principal Investigator
Headley Way
Headington
Oxford
OX3 9DU
United Kingdom
| emma.culver@nhs.net |
Scientific
1000 Winter Street
Waltham
02451-1438
United States of America
| Phone | +1 (0)857 273 0413 |
|---|---|
| allen.poma@zenasbio.com |
Study information
| Study design | Interventional double blind randomized parallel group placebo controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised parallel trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a participant information sheet |
| Scientific title | A Phase III, multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of obexelimab in patients with IgG4-related disease (INDIGO) |
| Study acronym | INDIGO |
| Study objectives | Administration of obexelimab will increase the time to first IgG4-RD flare that requires initiation of rescue therapy. |
| Ethics approval(s) | Approval pending, North West - Liverpool Central Research Ethics Committee (+44 (0)2071048118, +44 (0)20 7104 8222, +44 (0)2071048016; liverpoolcentral.rec@hra.nhs.uk), ref: 23/NW/0015 |
| Health condition(s) or problem(s) studied | IgG4-Related Disease |
| Intervention | Participants will be randomised in a 1:1 ratio to receive either obexelimab or placebo as a subcutaneous injection for 52 weeks. At the end of the 52 weeks of the randomized control period (RCP), participants will have the opportunity to continue in an open-label extension period (OLE), where all participants will receive obexelimab. Patients who do not wish to enroll into the open-label extension period will return for an in-clinic safety follow-up visit 8 weeks after the Week 52 visit (i.e., Week 60). |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | Obexelimab |
| Primary outcome measure | 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 outcome measures | There are no secondary outcome measures |
| Overall study start date | 01/01/2022 |
| Completion date | 31/12/2026 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | 200 |
| Key inclusion criteria | 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 4. Patients must have active IgG4-RD signs/symptoms (i.e., flare) that require the initiation of GC therapy or the increase in background long-term GC therapy 5. Other inclusion criteria apply |
| Key exclusion criteria | 1. Has disease in only one organ system whose primary manifestation is fibrosis 2. Has received prednisone equivalent given orally at a dose greater than 60 mg/day within the 4 weeks prior to screening or during screening 3. Has received a non-biologic, disease-modifying anti-rheumatological drug or immunosuppressive agent other than GCs within the 4 weeks prior to screening 4. 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 5. Has received live vaccine or live therapeutic infectious agent within the 2 weeks prior to screening 6. Active tuberculosis or high risk for tuberculosis; hepatitis C infection in absence of curative treatment; evidence of hepatitis B infection 7. Use of B cell depleting or targeting agents within 6 months of randomization 8. Other exclusion criteria apply |
| Date of first enrolment | 30/09/2022 |
| Date of final enrolment | 31/12/2024 |
Locations
Countries of recruitment
- Argentina
- Canada
- China
- England
- France
- Germany
- Hong Kong
- Hungary
- Italy
- Japan
- Korea, South
- Mexico
- Netherlands
- Poland
- Spain
- Sweden
- Taiwan
- Türkiye
- United Kingdom
- United States of America
Study participating centres
Headington
Oxford
OX3 9DU
United Kingdom
Great Maze Pond
London
SE1 9RT
United Kingdom
Sponsor information
Industry
1000 Winter Street
Waltham
MA 02451-1436
United States of America
| clinicaltrialsinfo@zenasbio.com |
Funders
Funder type
Industry
No information available
Results and Publications
| Intention to publish date | 31/12/2027 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Published as a supplement to the results publication |
| Publication and dissemination plan | Peer reviewed scientific journals Internal report Conference presentation Publication on website Submission to regulatory authorities Other |
| IPD sharing plan | The Sponsor is committed to the responsible sharing of clinical data with the goal of advancing medical science and improving patient care. Independent researchers will be permitted to use anonymised data collected from participants during this study to conduct additional scientific research, which may be unrelated to the study medication. This data will be obtained from study publications once the research has been completed. The data from study publications will not include identifiable information. |
Editorial Notes
02/05/2024: Internal review.
23/12/2022: Trial's existence confirmed by NHS HRA.
