A phase II Study of obexelimab in patients with relapsing multiple sclerosis
| ISRCTN | ISRCTN78327800 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN78327800 |
| EudraCT/CTIS number | 2024-512707-40 |
| IRAS number | 1010092 |
| ClinicalTrials.gov number | NCT06564311 |
| Secondary identifying numbers | ZB012-02-002, CPMS 61107 |
- Submission date
- 11/06/2024
- Registration date
- 26/11/2024
- Last edited
- 16/01/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Ongoing
- Condition category
- Nervous System Diseases
Plain English summary of protocol
Background and study aims
Multiple sclerosis (MS) is a potentially disabling autoimmune disease that affects the central nervous system (brain and spinal cord). B cells play an important role in the autoimmune disease mechanism. Obexelimab, an experimental study drug, is an antibody developed for the treatment of such autoimmune disorders. The drug acts by binding to the B cell surface and decreases B cell activity. The purpose of this study is to evaluate the safety and effectiveness of obexelimab, on MS.
Who can participate?
Patients ≥ 18 to ≤ 60 years of age with a diagnosis of relapsing-remitting or secondary progressive with relapses (RMS)
What does the study involve?
In Part A, obexelimab or placebo as subcutaneous injections, will be administered at random. Two-thirds of the patients will receive obexelimab and one-third will receive a placebo, once weekly for 12 weeks. After week 12, all patients will receive obexelimab in Part B, for an additional 12 weeks.
What are the possible benefits and risks of participating?
Taking part in this study may or may not help to treat the patient’s MS, however, the data collected may help doctors learn more about the study drug and whether it provides any benefit to patients with MS, which in turn may help future patients with MS.
All drugs have some risks, which may include things that could make the participant feel unwell, uncomfortable, or harm them.
Participants might have side effects related to the study drug and procedures while taking part in the study. Everyone taking part in the study will be watched for side effects; however, the study team do not know all the side effects that the study drug may have on the participant. These effects may be mild or serious. In some cases, these effects might be long-lasting, permanent, and may even be life-threatening. Participants should call the study doctor when they think they are having any problems.
The sponsor recognises that weekly IP administration is quite intensive, therefore the burden of this has been mitigated for visits where no clinic attendance is required by protocol, by allowing the option of home IP administration either via self, caregiver or utilisation of home care vendor services (Firma). IP administration is the only study procedure that Firma would be undertaking if required.
Obexelimab risks:
There have been 198 healthy volunteers and patients with autoimmune diseases treated with various doses of obexelimab as either intravenous infusion (158 patients) or subcutaneous injection (40 patients). Approximately 40 additional patients have been dosed with either obexelimab or placebo in patients with IgG4-RD and warm autoimmune hemolytic anaemia. Obexelimab affects the immune system and may cause serious infections. Obexelimab has side effects at the site of drug injection with the most common being bruising and redness. Most of these side effects were mild and lasted less than a day.
When obexelimab was given by intravenous infusion, there were serious cases of infusion reactions and non-serious abdominal discomfort including nausea, vomiting, and diarrhoea. These side effects have not been observed for obexelimab given as a subcutaneous injection.
Other common side effects included:
• Headache 8%
• Injection site bruising 8%
• Dizziness 5%
• Back pain 5%
• Injection site redness 5%
These events were mostly mild and temporary.
Risks from study test procedures:
• Injection site reactions: pain, redness, swelling, itching, or bruising at the site of the study drug injection.
• Blood sampling: Having blood taken from a vein may cause some pain, redness, or bruising at the injection site. An infection at the injection site is possible but rare.
• ECG: The ECG procedure may cause some mild discomfort during the placement and removal of the leads to and from the skin. The skin may become a little red or irritated. May also experience local irritation, redness, or burning in the areas where the leads are attached.
• MRI scan: There are risks from an MRI if participants are pregnant or have one of the following: an artificial heart valve, pacemaker, metal plate, pins, or other metallic objects in their body (including gunshot or shrapnel). Participants may also become anxious from lying in a tight space without moving. The MRI scan does not cause any pain and does not expose participants to X-ray radiation. For some MRI scans, participants may receive a contrast dye, given via vein using a small needle or plastic tube. Participants may feel local warmth or pain in the area where the dye is injected. The most common contrast material used for MRIs is gadolinium. Side effects from the dye may include nausea, vomiting, or headache. Participants will not be given the MRI contrast dye if they have abnormal kidney function. People with severe kidney insufficiency or chronic liver disease experiencing kidney insufficiency may develop a severe disease, called nephrogenic systemic fibrosis, from gadolinium. Nephrogenic systemic fibrosis triggers thickening of the skin, organs, and other tissues. The exact cause is unclear, and there is no effective treatment. Serious allergic reactions that may be life-threatening are very rare. Participants will be asked questions and may undergo tests to ensure that the MRI scan is safe for them.
• Chest X-ray: Chest X-rays involve exposure to a very small amount of ionising radiation. Ionising radiation can cause cancer many years or decades after the exposure. Participants are advised of the inherent risks in the ICF.
• Lumbar Puncture: Use of atraumatic or non-cutting lumbar puncture needles and screening techniques (ultrasound) may be used to reduce the risk of a post-lumbar puncture headache.
• Unforeseeable risks: Since obexelimab is an experimental study drug, there may be other risks that are unknown at this time. Participants are advised to seek medical assistance right away.
• Reproductive risks; The effects of obexelimab on human eggs, unborn children (including miscarriage), or nursing infants are not known at this time. Participants will not be eligible for participation if they are planning on becoming pregnant if they are pregnant, or if they are nursing.
Where is the study run from?
Zenas BioPharma (USA) LLC
When is the study starting and how long is it expected to run for?
June 2024 to January 2026
Who is funding the study?
Zenas BioPharma (USA) LLC
Who is the main contact?
allen.poma@zenasbio.com
Contact information
Scientific
1000 Winter Street, Suite 1200
Waltham
MA 02451
United States of America
| Phone | +1 857 2730413 |
|---|---|
| allen.poma@zenasbio.com |
Principal Investigator
Queen Mary, University of London, Whitechapel
London
E1 1BB
United Kingdom
| Phone | +44 (0)20 7882 8954 |
|---|---|
| g.giovannoni@qmul.ac.uk |
Study information
| Study design | Randomized placebo-controlled double-blind study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Safety, Efficacy |
| Scientific title | A phase II, multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of obexelimab, in patients with relapsing multiple sclerosis |
| Study objectives | To evaluate the effect of weekly SC administration of obexelimab versus placebo in patients with RMS on the prevention of new gad enhancing T1 (GdE T1) hyperintense lesions detected using MRI To evaluate the effect of weekly SC administration of obexelimab versus placebo in patients with RMS on: • Additional MRI endpoints • Neurofilament light chain (NfL) To evaluate the safety and tolerability of weekly SC administration of obexelimab in patients with RMS |
| Ethics approval(s) |
Approved 09/09/2024, London – Riverside REC (2 Redman Place, Stratford, London, E20 1JQ, United Kingdom; -; riverside.rec@hra.nhs.uk), ref: 24/LO/0508 |
| Health condition(s) or problem(s) studied | Relapsing multiple sclerosis |
| Intervention | Patients will be randomized 2:1 to obexelimab 250mg SC or matching placebo SC once weekly for 12 weeks, followed by an additional 12 weeks in which all patients will receive obexelimab 250mg SC. A follow-up visit will occur 8 weeks after the final dose. Randomization will be performed using Interactive Response Technology. |
| Intervention type | Biological/Vaccine |
| Pharmaceutical study type(s) | Pharmacokinetic, Pharmacodynamic, Therapy, Others (Tolerability) |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | Obexelimab [Obexelimab] |
| Primary outcome measure | Cumulative number of new GdE T1 hyperintense lesions measured by brain MRI over Week 8 and 12 |
| Secondary outcome measures | 1. Cumulative number of new and/or enlarging T2 weighted hyperintense lesions measured by brain MRI over Week 8 and Week 12 2. Number of new GdE T1 hyperintense lesions measured by brain MRI at Weeks 4, 8, and 12 3. Change from baseline in volume of T2 lesions measured by brain MRI at Week 12 4. Serum neurofilament lightchain measured by a blood test at Week 12 5. Incidence of AEs, SAEs, including injection site reactions and hypersensitivity reactions, and AESI, as defined by the CTCAE v5.0 from date of informed consent until end of study |
| Overall study start date | 07/06/2024 |
| Completion date | 31/01/2026 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 60 Years |
| Sex | Both |
| Target number of participants | 93 |
| Key inclusion criteria | 1. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF 2. Male or female, ≥ 18 to ≤ 60 years of age, inclusive, at the time of signing the ICF 3. Diagnosis of RMS (relapsing-remitting or secondary progressive with relapses) according to the 2017 revision of the McDonald diagnostic criteria 4. An EDSS of ≤ 5.5 at the Screening Visit 5. Must have documentation of: 5.1. at least 1 relapse within the previous year OR 5.2. ≥ 2 relapses within the past 2 years OR 5.3. ≥ 1 active Gd-enhancing brain lesion on an MRI scan within the past 6 months before screening 6. A female patient is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies: 6.1. Not a woman of childbearing potential (WOCBP) as defined in Appendix 4 OR 6.2. A WOCBP who agrees to follow the contraceptive guidance in Appendix 4 until at least 8 weeks after the last administration of IMP AND 6.3. Has a negative serum pregnancy test at screening and a negative urine pregnancy test on Day 1 before the first dose of IMP AND 6.4. Agrees to refrain from egg donation until at least 8 weeks after the last administration of IMP 7. A male patient must: 7.1. Agree to either (i) abstain from intercourse or (ii) use contraception (as detailed in Appendix 4) until at least 8 weeks after the last administration of IMP, or (iii) be surgically sterile for the duration of the study AND 7.2. Agree to refrain from donating sperm until at least 8 weeks after the last administration of IMP |
| Key exclusion criteria | 1. Primary progressive MS or secondary progressive MS without relapses 2. Meet criteria for neuromyelitis optica spectrum disorder 3. Relapse in the 30 days prior to randomization 4. ≥ 10 years disease duration from the onset with patient’s EDSS ≤ 2.0 (patient-reported is adequate in absence of written medical record) 5. Has > 20 Gd+ lesions on brain MRI at screening 6. Prior use of B cell–depleting agents 7. Prior use of other biologic immunomodulatory agents ≤ 6 months before randomization 8. Has received systemic corticosteroids or adrenocorticotropic hormone within 1 month (30 days) before screening MRI 9. Has received dimethyl fumarate within 1 month before randomization 10. Has received treatment with B-interferons or glatiramer acetate within 1 month before randomization 11. Has received treatment with intravenous immunoglobulins, plasmaphereses, sphingosine-1-phosphate treatments, or natalizumab (patients who stop getting infusions within 6 months before randomization should be ruled out for progressive multifocal leukoencephalopathy) within 2 months before randomization 12. Has received azathioprine or methotrexate within 6 months before randomization 13. Has received treatment with teriflunomide within 3 months to randomization (unless elimination procedure was done) 14. Has received cladribine, cyclophosphamide, alemtuzumab, or mitoxantrone within 2 years before randomization 15. Has received lymphoid irradiation or stem cell transplantation 16. 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 longer, before randomization 17. Has received a live vaccine or live therapeutic infectious agent within the 4 weeks before randomization 18. History of drug or alcohol abuse in the previous 12 months before screening in the opinion of the investigator 19. Acute hepatitis B infection (hepatitis B surface antigen-positive), active hepatitis C virus, or HIV infection. Patients will be excluded from the study if they have a positive test for active hepatitis B by detecting (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. Patients with active, chronic or uncured HBV will be excluded. 20. Evidence of active tuberculosis (TB) or at high risk for TB as shown by at least one of the following: 20.1. Documented history of active TB or latent TB, unless completion of treatment according to local guidelines 20.2. 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 20.3. Signs or symptoms that could represent active TB 20.4. Chest radiograph, computed tomography, or MRI that suggests possible diagnosis of TB 21. Malignancy within 5 years except successfully treated in situ cervical cancer, resected squamous cell or basal cell carcinoma of the skin 22. Hematology or clinical chemistry parameters that meet any of the following criteria at screening: 22.1. White blood cell count < 3.5 × 10^3/μL 22.2. Absolute neutrophil count < 1.5 × 10^3/μL 22.3. Elevated serum creatinine > 2.5 × upper limit of normal (ULN) OR estimated creatinine clearance < 40 mL/min calculated by the Cockcroft-Gault formula at screening 22.4. Hemoglobin < 10 g/dL 22.4. Platelet count < 75 × 10^3/μL 23. Abnormal liver function tests meeting any of the following criteria: 23.1. Alanine aminotransferase > 2 × ULN 23.2. Aspartate aminotransferase > 2 × ULN 23.3. Total bilirubin > 1.5 × ULN 24. 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 RMS that, in the opinion of the investigator, would pose a risk to patient safety or interfere with the study evaluation, procedures, or completion 25. Any known allergy to mAb therapy 26. Hypersensitivity to dextran or components of dextran or any component of the study drug and placebo, including excipients 27. Inability to comply with MRI scanning or MRI contrast administration |
| Date of first enrolment | 06/08/2024 |
| Date of final enrolment | 31/03/2025 |
Locations
Countries of recruitment
- Austria
- Belgium
- China
- Croatia
- Denmark
- England
- Greece
- Italy
- Poland
- Spain
- United Kingdom
- United States of America
- Wales
Study participating centres
London
E1 1BB
United Kingdom
Cwmrhydyceirw
Swansea
SA6 6NL
United Kingdom
Leicester
LE5 4PW
United Kingdom
Harlow
CM20 1QX
United Kingdom
Basildon
SS16 5NL
United Kingdom
Westcliff-on-sea
SS0 0RY
United Kingdom
Broomfield
Chelmsford
CM1 7ET
United Kingdom
Croydon
CR9 2PQ
United Kingdom
Charter Way
Turner Road
Colchester
CO4 5JL
United Kingdom
Sponsor information
Industry
1000 Winter Street, Suite 1200
Waltham, MA
02451
United Kingdom
| Phone | +1 857 273 0413 |
|---|---|
| allen.poma@zenasbio.com |
Funders
Funder type
Industry
No information available
Results and Publications
| Intention to publish date | 01/12/2030 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | 1. Peer reviewed scientific journals 2. Internal report 3. Conference presentation 4. Publication on website 5. Submission to regulatory authorities 6. Other |
| IPD sharing plan | The data-sharing plans for the current study are unknown and will be made available at a later date. The sponsor, PPD, part of Thermo Fisher Scientific and regulatory authorities will be granted direct access to medical records for verification of study procedures and data without violating the confidentiality of the records to the extent permitted by the applicable laws and regulations. Before data transfer all identifiable information will be replaced by a code. The sponsor shall ensure that the necessary measures are taken to protect and maintain the confidentiality of data when transferred outside of the UK and EEA. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol file | version 1.0 | 22/03/2024 | 29/10/2024 | No | No |
Additional files
Editorial Notes
16/01/2025: Internal review.
11/09/2024: ISRCTN received notification of combined HRA/MHRA approval for this trial on 11/09/2024
11/06/2024: Study's existence confirmed by Health Research Authority (HRA) (UK).
