A Phase 3 Study of Obexelimab in Patients with Warm Autoimmune Hemolytic Anemia

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

22 Sep 2023 → 28 Aug 2025

Decision date (initial)

2023-07-19

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Zenas BioPharma (USA) LLC

External identifiers

EU CT number

2022-501005-12-00

WHO UTN

U1111-1281-7206

ClinicalTrials.gov

NCT05786573

ISRCTN

ISRCTN13110963

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety, Others

Part A: Safety and Dose Confirmation Run-in Period (SRP)
- To evaluate the safety and tolerability of weekly subcutaneous (SC) administration of obexelimab in patients with wAIHA
- To evaluate the clinical benefit of weekly SC administration of obexelimab on anemia in patients with wAIHA

Part B: Randomized Control Period (RCP)
- To evaluate the clinical benefit of weekly SC administration of obexelimab on anemia in patients with wAIHA

Part C: Open-Label Extension (OLE) Period
- To evaluate the safety and tolerability of weekly SC administration of obexelimab in patients with wAIHA
- To evaluate Hgb response and total duration of response of weekly SC administration of obexelimab in patients with wAIHA
- To evaluate the clinical benefit of weekly SC administration of obexelimab on rescue therapy use in patients with wAIHA

Secondary objectives 1

1. Part A: Safety and Dose Confirmation Run-in Period (SRP) - To evaluate the clinical benefit of weekly SC administration of obexelimab on other measures of disease activity in patients with wAIHA, Part B: Randomized Control Period (RCP) - To evaluate the clinical benefit of weekly SC administration of obexelimab on other measures of disease activity in patients with wAIHA - To evaluate the safety and tolerability of weekly SC administration of obexelimab in patients with wAIHA

Conditions and MedDRA coding

WARM AUTOIMMUNE HEMOLYTIC ANEMIA

Study design 3 periods

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 20

1. PARTS A AND B: INCLUSION CRITERIA 1. Males and females ≥ 18 years of age at the time of signing the informed consent
2. 2. Diagnosed with wAIHA for at least 3 months and currently receiving treatment for wAIHA or have previously received treatment for wAIHA (treatment-naive patients are not eligible)
3. 3. Diagnosis of primary or secondary wAIHA as documented by a positive DAT specific for anti-IgG or anti-IgA
4. 4. Failed at least 1 prior wAIHA treatment regimen, including steroids, rituximab, azathioprine, cyclophosphamide, cyclosporine, mycophenolate mofetil, danazol, vincristine, erythropoiesis-stimulating agents, or splenectomy (folate, iron, or other supplements do not fulfill this criterion). Failure is defined as a drop in Hgb of ≥ 1 g/dL and an increase in LDH of ≥ 1.5 × upper limit of normal (ULN) after a minimum of 4 weeks of GC therapy, or 3 months of immunosuppression therapy, respectively.
5. 5. For the SRP (Part A) only, if on prednisone/prednisolone, the dose may not exceed 30 mg/day and must have been stable for at least 4 weeks prior to enrollment. Patients must remain on the stable dose throughout the SRP, except for patients on doses of >20 mg to ≤ 30 mg/day who may taper to no less than 20 mg/day and remain on a stable dose thereafter once they have achieved the primary endpoint and have a Hgb response on 2 consecutive in-clinic visits. For the RCP (Part B), if on prednisone/prednisolone, the dose may not exceed 20 mg/day and must have been stable for at least 4 weeks prior to randomization and remain stable throughout the RCP
6. 6. If receiving immunosuppressants, must have been on a stable dose for at least 12 weeks prior to enrollment (SRP) or randomization (RCP) and remain on a stable dose throughout the SRP or RCP. Allowed concomitant immunosuppressants are azathioprine, mycophenolate mofetil/mycophenolic acid, cyclosporine, and cyclophosphamide
7. 7. Hgb ≥ 7 to < 10 g/dL
8. 8. At least one sign or symptom of anemia as assessed by the investigator at screening
9. 9. Screening platelet count ≥ 50,000 mm3
10. 10. Screening neutrophil count ≥ 1,000 mm3
11. 11. Screening serum albumin and serum calcium concentrations within the normal range
12. 12. Screening total serum IgG of ≥ 400 mg/dL
13. 13. Screening creatine kinase value < 2 × ULN
14. 14. Patients with a history of splenectomy must be at least 4 months post resection prior to enrollment (SRP) or randomization (RCP) and must be vaccinated as per country-specific immunization schedules
15. 15. Patients with autoimmune disorders (e.g., systemic lupus erythematosus, rheumatoid arthritis) may be eligible if they are receiving stable treatment (no changes in disease- related concomitant medications), and the severity of disease has been stable for at least 4 months prior to enrollment (SRP) or randomization (RCP)
16. 16. Removed in Amendment 2 v3.0
17. 17. Females not pregnant (see Appendix 4), not breastfeeding, and for whom at least one of the following conditions applies: a. Not of childbearing potential, as defined in Appendix 4 OR b. FOCBP with a negative serum pregnancy test at screening and a negative urine pregnancy test prior to the first dose of study drug and agreement to follow the contraceptive guidance in Appendix 4 for the duration of the study and for at least 8 weeks after the last administration of study drug c. Agree to refrain from egg donation until at least 8 weeks after the last dose of study drug
18. 18. Males for whom the following conditions apply: a. Agree to (i) abstain from intercourse or (ii) use contraception (as detailed in Appendix 4) for the duration of the study and for 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 for the duration of the study and for at least 8 weeks after the last dose of IMP
19. 19. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol
20. PART C: OLE PERIOD INCLUSION CRITERIA 1. Completed the Week 24 SRP or RCP visit 2. Have not had IMP discontinued due to any of the following safety reasons: a. Pregnancy b. Malignancy c. Hypersensitivity to IMP d. Determination that the patient was ineligible for the SRP and RCP e. For any reason deemed necessary by the investigator for patient safety 3. Have not discontinued from IMP due to unblinding of a patient 4. FOCBP must have a negative serum pregnancy test prior to enrollment in the OLE Period 5. Have not received a transfusion within 2 weeks prior to first dose in the OLE Period 6. Not receiving more than 2 concomitant medications for the treatment of wAIHA, excluding vitamins or other supplements, at the time of enrollment in the OLE Period 7. Patients must receive first dose of obexelimab in the OLE Period within 14 days of the Week 24 SRP/RCP visit 8. Willing to comply with all study protocol procedures and complete all study visits

Exclusion criteria 23

1. PARTS A AND B: EXCLUSION CRITERIA 1. Have cold antibody AIHA, cold agglutinin syndrome, mixed type (i.e., warm and cold) AIHA, or paroxysmal cold hemoglobinuria
2. 2. Have any other associated cause of hereditary or acquired hemolytic anemia
3. 3. Removed in Amendment 2 v3.0
4. 4. Received a transfusion within 2 weeks prior to enrollment (SRP) or randomization (RCP)
5. 5. Use of B cell–depleting, B cell–targeted, or other biologic immunomodulatory agents within the 6 months prior to enrollment (SRP) or randomization (RCP). Patients who received B cell–targeted therapy within 6 to 12 months prior to randomization must have a B cell count at screening that is within the laboratory reference range, as measured by the central laboratory
6. 6. Received IV Ig or epoetin alfa within 6 weeks prior to enrollment (SRP) or randomization (RCP). The patient may be re-screened after the exclusionary period of 6 weeks has passed
7. 7. Receiving more than 2 concomitant medications for the treatment of wAIHA, excluding vitamins or other supplements, at the time of screening
8. 8. Received an investigational treatment or direct medical intervention in another clinical study within 12 weeks or < 5 half-lives of the investigational treatment, whichever is shorter, prior to screening
9. 9. Received live vaccine or live therapeutic infectious agent within the 6 weeks prior to enrollment (SRP) or randomization (RCP)
10. 10. Evidence of active tuberculosis (TB) or at high risk for TB based on at least one of the following: a. History of active TB or latent TB, unless completion of treatment according to local guidelines is documented b. Positive, indeterminate, or invalid interferon-gamma (IFNγ) 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 scan, or magnetic resonance imaging that suggests possible diagnosis of TB
11. 11. 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), that, in the opinion of the investigator, would pose a risk to patient safety or interfere with the study evaluations, procedures, or completion
12. 12. Known allergy to mAb therapy
13. 13. Known hypersensitivity to dextran or components of dextran
14. 14. Active infection (e.g., pneumonia, biliary tract infection, diverticulitis, Clostridium difficile infection) that requires parenteral or oral anti-infectives and/or hospitalization, and/or is assessed as serious/clinically significant by the investigator, within 8 weeks prior to screening. Patients may be re-screened after the 8-week exclusionary period has passed
15. 15. Chronic infection (e.g., bronchiectasis, chronic osteomyelitis, chronic pyelonephritis) or requiring chronic treatment with anti-infectives (e.g., antibiotics, antivirals)
16. 16. Confirmed or suspected clinical immunodeficiency syndrome not related to treatment of wAIHA, or has a family history of congenital or hereditary immunodeficiency, unless confirmed absent in the patient
17. 17. Acute hepatitis B infection (hepatitis B surface antigen-positive), active hepatitis C virus (HCV), 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. In Japan, patients will be excluded if there is detection of (a) hepatitis B surface antigen or (b) hepatitis B surface antibody or (c) hepatitis B core antibody. Patients with a history of HCV will be excluded in the study unless there is documentation of a negative HCV ribonucleic acid level in the serum at 12 weeks or longer after the completion of HCV therapy
18. 18. Intend to become pregnant, breastfeed, or are planning egg or sperm donation during the study or within 8 weeks after the last dose of study drug
19. 19. Current alcohol/substance abuse/dependence, a history of alcohol/substance abuse/dependence within the 12 months prior to enrollment (SRP) or randomization (RCP), or, in the investigator’s opinion, there is evidence of ongoing alcohol/substance abuse/dependence
20. 20. Major surgery (surgery requiring hospitalization ≥ 3 days or with a high risk of re-bleeding) within 4 months prior to enrollment (SRP) or randomization (RCP) or have plans for or have been scheduled for any elective surgery or major dental procedure during the study
21. 21. Have a history of a major organ transplant (e.g., heart, lung, kidney, liver) or hematopoietic stem cell/marrow transplant
22. 22. Malignancy within 5 years of enrollment (SRP) or randomization (RCP)
23. 23. Commitment to an institution by virtue of an order issued either by the judicial or the administrative authorities

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 7

1. Incidence of AEs, SAEs, and any AESIs, as defined by the CTCAE v5.0
2. Proportion of patients with Hgb ≥ 10 g/dL and ≥ 2 g/dL increase from Baseline on or after Week 8 with no use of blood transfusion or GC rescue therapy prior to attaining response
3. Proportion of patients who achieve a durable Hgb response (defined as Hgb ≥ 10 g/dL and ≥ 2 g/dL increase from Baseline on at least 3 of 4 consecutive available visits), at the earliest on or after Week 12, with no use of blood transfusion or GC rescue therapy prior to attaining durable response through Week 24
4. Incidence of AEs, SAEs, and any AESIs, as defined by the CTCAE v5.0
5. Proportion of patients with Hgb ≥ 10 g/dL and ≥ 2 g/dL increase from Baseline, with no use of blood transfusion or GC rescue therapy
6. Time in Hgb response in patients achieving durable Hgb response
7. Cumulative dose of GC rescue therapy

Secondary endpoints 20

1. Change from Baseline in FACIT-F score through Week 24
2. Proportion of patients with no use of blood transfusion or GC rescue therapy through Week 24
3. Proportion of patients who achieve a durable Hgb response (defined as Hgb ≥ 10 g/dL and ≥ 2 g/dL increase from Baseline on at least 3 of 4 consecutive available visits) at the earliest on, or after Week 8, with no use of blood transfusion or GC rescue therapy prior to attaining durable response through Week 24
4. Proportion of patients who attain normal values on or after Week 8 with no use of blood transfusion or GC rescue therapy prior to response: – Lactate dehydrogenase (LDH) – Haptoglobin – Indirect bilirubin
5. Change from Baseline to Week 24 in Hgb concentration
6. Time to Hgb ≥ 10 g/dL and ≥ 2 g/dL increase from Baseline, with no use of blood transfusion or GC rescue therapy
7. Proportion of patients with no use of blood transfusions through Week 24
8. Obexelimab serum concentrations through Week 24
9. Incidence of anti-obexelimab antibodies through Week 24
10. "Change from Baseline through Week 24 over time in the following: – Circulating absolute T, B, and NK cell count – Ig levels and ratios (e.g., IgG, IgM, IgA, IgE) – CD19 target receptor occupancy – Reticulocyte count – LDH – Haptoglobin – Indirect bilirubin"
11. Change from Baseline to Week 24 in FACIT-F Score
12. Proportion of patients with no use of blood transfusion or GC rescue therapy through Week 24
13. Cumulative dose of GC rescue therapy through Week 24
14. Proportion of patients with no use of blood transfusions through Week 24
15. Change from Baseline to Week 24 in Hgb concentration
16. "Proportion of patients who attain normal values on at least 3 of 4 consecutive available visits, at the earliest on or after Week 12, with no use of blood transfusion or GC rescue therapy prior to attaining durable response through Week 24 in all 3 of the following: – LDH – Haptoglobin – Indirect bilirubin"
17. Proportion of patients with a ≥ 3-point increase in FACIT-F score at Week 24, with no prior use of blood transfusion or GC rescue therapy
18. Time to durable Hgb response, in patients who achieve the primary endpoint
19. Percentage of time in Hgb response, on or after Week 4 through Week 24, in patients who achieve the primary endpoint
20. Incidence of AEs, SAEs, and any AESIs, as defined by the 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 14

Locations

3 EU/EEA countries · 6 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 76 files

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

Application history

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