A Phase 2 Study of Obexelimab in Patients with Relapsing Multiple Sclerosis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Zenas Biopharma (USA) LLC

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

7 Nov 2024 → ongoing

Decision date (initial)

2024-10-02

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Zenas BioPharma (USA) LLC

External identifiers

EU CT number

2024-512707-40-00

WHO UTN

U1111-1302-2972

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Efficacy, Therapy, Others, Pharmacodynamic

To evaluate the effect of weekly subcutaneous (SC) administration of obexelimab versus placebo in patients with relapsing multiple sclerosis (RMS) on the prevention of new gadolinium -enhancing T1 (GdE T1) hyperintense lesions detected using magnetic resonance imaging (MRI)

Secondary objectives 2

1. To evaluate the effect of weekly SC administration of obexelimab versus placebo in patients with RMS on: • Additional MRI endpoints; • Neurofilament light chain (NfL)
2. To evaluate the safety and tolerability of weekly SC administration of obexelimab in patients with RMS

Conditions and MedDRA coding

RELAPSING MULTIPLE SCLEROSIS

Study design 5 periods

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. 1. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF
2. 2. Male or female, ≥ 18 to ≤ 60 years of age, inclusive, at the time of signing the ICF
3. 3. Diagnosis of RMS (relapsing-remitting or active secondary progressive) according to the 2017 revision of the McDonald diagnostic criteria
4. 4. An EDSS of ≤ 5.5 at the Screening Visit
5. 5. Must have documentation of: a. at least 1 relapse within the previous year OR b. ≥ 2 relapses within the past 2 years OR c. ≥ 1 active Gd-enhancing brain lesion on an MRI scan within the past 6 months prior to screening
6. 6. A female patient is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies: a. Not a woman of childbearing potential (WOCBP) as defined in Appendix 4 OR b. A WOCBP who agrees to follow the contraceptive guidance in Appendix 4 until at least 8 weeks after the last administration of IMP AND c. Has a negative serum pregnancy test at screening and a negative urine pregnancy test at Day 1 prior to the first dose of IMP AND d. Agrees to refrain from egg donation until at least 8 weeks after the last administration of IMP
7. 7. A male patient must: a. 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 b. Agree to refrain from donating sperm until at least 8 weeks after the last administration of IMP

Exclusion criteria 28

1. 1. Primary progressive MS or inactive secondary progressive MS
2. 25. Any known allergy to mAb therapy
3. 7. Prior use of other biologic immunomodulatory agents ≤ 6 months prior to randomization
4. 17. Has received live vaccine, live-attenuated vaccine, or live therapeutic infectious agent within the 4 weeks prior to randomization
5. 15. Has received lymphoid irradiation or stem cell transplantation
6. 8. Has received systemic corticosteroids or adrenocorticotropic hormone within 1 month (30 days) prior to screening MRI
7. 12. Has received azathioprine or methotrexate within 6 months prior to randomization
8. 9. Has received dimethyl fumarate within 1 month prior to randomization
9. 23. Abnormal liver function tests meeting any of the following criteria: a. Alanine aminotransferase > 2 × ULN b. Aspartate aminotransferase > 2 × ULN c. Total bilirubin > 1.5 × ULN
10. 11. Has received treatment with intravenous immunoglobulins, plasmapheresis or natalizumab (patients who stop getting infusions within 6 months prior to randomization should be ruled out for progressive multifocal leukoencephalopathy) within 2 months prior to randomization. Has received sphingosine 1-phosphate receptor modulator treatment within 5 half-lives of the treatment or until the end of its pharmacodynamic activity, or whichever is longer, prior to randomization (for example; Ponesimod [Ponvory®]: 2 weeks, Siponimod [Mayzent®]: 1 month, Fingolimod [Gilenya®]: 2 months, Fingolimod oral disintegrating tablets [ODT] [Tascenso ODT®]: 2 months, Ozanimod [Zeposia®]: 3 months)
11. 26. Hypersensitivity to dextran or components of dextran or any component of the study drug and placebo, including excipients
12. 4. ≥ 10 years disease duration from onset with patient’s EDSS ≤ 2.0 (patient reported is adequate in absence of written medical record)
13. 10. Has received treatment with B-interferons or glatiramer acetate within 1 month prior to randomization
14. 14. Has received cladribine, cyclophosphamide, alemtuzumab, or mitoxantrone within 2 years prior to randomization
15. 21. Malignancy within 5 years except successfully treated in situ cervical cancer, resected squamous cell carcinoma, or basal cell carcinoma of the skin
16. 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 through detection of (a) hepatitis B surface antigen or (b) hepatitis B core antibody. Patients with active, chronic, or uncured HBV will be excluded.
17. 2. Meet criteria for neuromyelitis optica spectrum disorder
18. 3. Relapse in the 30 days prior to randomization
19. 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
20. 27. Inability to comply with MRI scanning or MRI contrast administration
21. 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 prior to randomization
22. 20. 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 or symptoms that could represent active TB d. Chest radiograph, computed tomography, or MRI that suggests possible diagnosis of TB
23. 5. Has > 20 Gd+ lesions on brain MRI at screening
24. 6. Prior use of B cell–depleting agents
25. 22. Hematology or clinical chemistry parameters that meet any of the following criteria at screening: a. White blood cell count < 3.5 × 10^3/μL b. Absolute neutrophil count < 1.5 × 10^3/μL c. 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 d. Hemoglobin < 10 g/dL e. Platelet count < 75 × 10^3/μL
26. 13. Has received treatment with teriflunomide within 3 months to randomization (unless elimination procedure was done)
27. 18. History of drug or alcohol abuse in the previous 12 months before screening in the opinion of the investigator
28. 28. History of Gilbert’s syndrome

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Cumulative number of new GdE T1 hyperintense lesions over Week 8 and Week 12, as measured by brain MRI

Secondary endpoints 5

1. Cumulative number of new and/or enlarging T2 weighted hyperintense lesions detected over Week 8 and Week 12
2. Number of new GdE T1 hyperintense lesions at Week 4, Week 8, and Week 12
3. Change from baseline in volume of T2 lesions at Week 12
4. Change from baseline in serum NfL at Week 12
5. Incidence of adverse events (AEs), serious adverse events (SAEs), and AEs of special interest, (AESI), as defined by the Common Terminology of Criteria for Adverse Events (CTCAE) Version 5.0

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 9

Locations

10 EU/EEA countries · 24 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 138 files

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

Application history

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