Study of NM8074 in Patients with Anti-Neutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis (AAV)

NCT06226662 | Not Yet Recruiting Phase 2 FDA Drug

• 1 other identifier: NM8074-AAV-501
• Study Type: interventional
• Target: 12
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a Randomized, Double-Blind, Placebo-Controlled Study designed to assess safety, tolerability, and efficacy of NM8074 in AAV patients when used in combination with Standard of Care (SOC) cyclophosphamide/azathioprine or rituximab plus corticosteroids.

Conditions

Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis

Outcome Measures

Primary Outcomes (1)

• Proportion of subjects achieving disease response at Day 85 defined as BVAS percent decrease of at least 50% from baseline.

  Up to Study Day 85

Secondary Outcomes (12)

• Number of patients with ANCA positivity (anti-PR3 and anti-MPO)

  Up to Study Day 133

• Change from Baseline or Percent Change from Baseline in BVAS (Birmingham Vasculitis Activity Score)

  Up to Study Day 133

• Change from Baseline or Percent Change from Baseline in Vasculitis Damage Index (VDI)

  Up to Study Day 133

• Change from Baseline or Percent Change from Baseline in C-reactive protein concentration

  Up to Study Day 133

• Proportion of patients requiring rescue glucocorticoid treatment

  Up to Study Day 133

Other Outcomes (6)

• Change from Baseline or Percent Change from Baseline in Classical Pathway (CP) modulation

  Up to Study Day 133

• Change from Baseline or Percent Change from Baseline in Factor B levels

  Up to Study Day 133

• Change from Baseline or Percent Change from Baseline in plasma concentration of NM8074

  Up to Study Day 133

Study Arms (2)

NM8074

EXPERIMENTAL

6 subjects will receive a biweekly dose of 20 mg/kg of NM8074 plus SOC (cyclophosphamide/azathioprine or rituximab plus corticosteroids)

Drug: NM8074

Placebo

PLACEBO COMPARATOR

6 subjects will receive a biweekly dose of placebo plus SOC (cyclophosphamide/azathioprine or rituximab plus corticosteroids)

Drug: Placebo

Interventions

NM8074 DRUG

NM8074 will be administered as an intravenous infusion. In Cohort 1, all subjects will be administered 20 mg/kg of NM8074 intravenously every two weeks for a total of 7 doses from Day 1 to Day 85 of the Treatment Period.

NM8074

Placebo DRUG

Saline Placebo will be administered as an intravenous infusion. In Cohort 2, all subjects will be administered saline placebo intravenously every two weeks for a total of 7 doses from Day 1 to Day 85 of the Treatment Period.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Clinical diagnosis of granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), or renal limited vasculitis.
• Male and female subjects aged at least 18 years, with newly diagnosed or relapsed Associated Vasculitis (AAV) where treatment with cyclophosphamide or rituximab is needed.
• At least 1 major item, or at least 3 non-major items, or at least the 2 renal items of proteinuria and hematuria on Birmingham Vasculitis Activity Score (BVAS).
• Estimated glomerular filtration rate (eGFR) ≥ 20 mL/ minute.
• Positive ANCA Test: indirect immunofluorescence (IIF) test for P-ANCA or C-ANCA, or positive ELISA test for anti-proteinase-3 (PR3) or anti-myeloperoxidase (MPO) at Screening.
• All patients must be vaccinated prior to dosing with MenACWY Menactra® polysaccharide diphtheria toxoid conjugate vaccination against Neisseria meningitidis serogroups A, C, Y, and W-135. Meningitis B (MenB) meningococcal serogroup B vaccine (Bexsero®) will be administered per local guidelines. If the window of vaccination is short, then patients will be prophylactically treated with appropriate antibiotics. Patients will also be required to have confirmation or administration of vaccination against S. pneumoniae and H. influenzae.
• Willing and able to understand and complete informed consent procedures, including signing and dating the informed consent form (ICF), and complying with the study visit schedule.
• Female partners of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, must have a negative pregnancy test at screening and must agree to use highly effective methods of contraception during dosing and for at least 8 weeks after stopping the investigational drug, and for at least 6 months after the last cyclophosphamide dose (if receiving cyclophosphamide) and at least 12 months after the last rituximab dose (if receiving rituximab).
• Male patients and partners of child-bearing potential must agree to use contraceptives and male patients must agree to refrain from donating sperm for the duration of the study.

You may not qualify if:

• Severe disease as determined by alveolar hemorrhage, hemoptysis, rapid onset mononeuritis multiplex or central nervous system involvement.
• Patients with rapidly progressive glomerulonephritis
• Any other known multi-system autoimmune disease including eosinophilic granulomatosis with polyangiitis (EGPA, Churg Strauss), systemic lupus erythematosus, Immunoglobulin A (lgA) vasculitis (HenochSchönlein purpura), rheumatoid vasculitis, Sjogren's disease, anti
• glomerular basement membrane disease, or cryoglobulinemia.
• Required dialysis or plasma exchange within 12 weeks prior to screening.
• Have a kidney transplant or disease.
• Received cyclophosphamide within 12 weeks prior to screening; if on azathioprine, mycophenolate mofetil or methotrexate at the time of screening, these drugs must be withdrawn prior to receiving the cyclophosphamide or rituximab dose on Day 1.
• Received intravenous glucocorticoids, \>3000 mg methylprednisolone equivalent, within 4 weeks prior to screening.
• Have been taking an oral daily dose of a glucocorticoid of more than 10 mg prednisone-equivalent for more than 6 weeks continuously prior to screening.
• Received rituximab or other B-cell antibody within 52 weeks of screening or 26 weeks provided B cell reconstitution has occurred (i.e., Cluster of Differentiation 19 (CD19) count \> 0.01x10\^9/L); received anti-tumor necrosis factor (TNF) treatment or other complement inhibitor treatment within 12 weeks prior to screening.
• Currently or previously under other complement inhibitor treatments less than 3 months prior to study Day 1.
• Patients who need the initiation of renal replacement therapy within 7 days
• Have any other clinically significant abnormal laboratory value in the opinion of the investigator.
• History of bone marrow, hematopoietic stem cell, or solid organ transplantation.
• History of currently active primary or secondary immunodeficiency.

Sponsors & Collaborators

• NovelMed Therapeutics: lead

Related Publications (5)

• Tesar V, Hruskova Z. Complement Inhibition in ANCA-Associated Vasculitis. Front Immunol. 2022 Jul 8;13:888816. doi: 10.3389/fimmu.2022.888816. eCollection 2022.

  PMID: 35880179 BACKGROUND

• Xiao H, Hu P, Falk RJ, Jennette JC. Overview of the Pathogenesis of ANCA-Associated Vasculitis. Kidney Dis (Basel). 2016 Mar;1(4):205-15. doi: 10.1159/000442323. Epub 2015 Dec 3.

  PMID: 27536680 BACKGROUND

• Chung SA, Langford CA, Maz M, Abril A, Gorelik M, Guyatt G, Archer AM, Conn DL, Full KA, Grayson PC, Ibarra MF, Imundo LF, Kim S, Merkel PA, Rhee RL, Seo P, Stone JH, Sule S, Sundel RP, Vitobaldi OI, Warner A, Byram K, Dua AB, Husainat N, James KE, Kalot MA, Lin YC, Springer JM, Turgunbaev M, Villa-Forte A, Turner AS, Mustafa RA. 2021 American College of Rheumatology/Vasculitis Foundation Guideline for the Management of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis. Arthritis Rheumatol. 2021 Aug;73(8):1366-1383. doi: 10.1002/art.41773. Epub 2021 Jul 8.

  PMID: 34235894 BACKGROUND

• Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group. KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. Kidney Int. 2021 Oct;100(4S):S1-S276. doi: 10.1016/j.kint.2021.05.021. No abstract available.

  PMID: 34556256 BACKGROUND

• Hellmich B, Sanchez-Alamo B, Schirmer JH, Berti A, Blockmans D, Cid MC, Holle JU, Hollinger N, Karadag O, Kronbichler A, Little MA, Luqmani RA, Mahr A, Merkel PA, Mohammad AJ, Monti S, Mukhtyar CB, Musial J, Price-Kuehne F, Segelmark M, Teng YKO, Terrier B, Tomasson G, Vaglio A, Vassilopoulos D, Verhoeven P, Jayne D. EULAR recommendations for the management of ANCA-associated vasculitis: 2022 update. Ann Rheum Dis. 2024 Jan 2;83(1):30-47. doi: 10.1136/ard-2022-223764.

  PMID: 36927642 BACKGROUND

MeSH Terms

Conditions

Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis

Condition Hierarchy (Ancestors)

Systemic Vasculitis; Vasculitis; Vascular Diseases; Cardiovascular Diseases; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Central Study Contacts

Rekha Bansal, PhD

CONTACT

2164402696; clinicalsae@novelmed.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: This is a double-blind study (subjects and on-site medical/nursing staff at the study site are blinded to study drug/dose assignment). The pharmacy staff preparing the investigational products will not be blinded to NM8074 study drug assignment, but all other site staff, including the Investigator, will be blinded. Unblinding should only be considered for the safety of the subject.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Eligible subjects will be enrolled and stratified in three strata: (1) granulomatosis with polyangiitis (GPA) (2) microscopic polyangiitis (MPA), and (3) renal-limited vasculitis, and then randomized in a 1:1 ratio of NM8074+SOC to Placebo+SOC (6 subjects in each cohort).

Study Record Dates

• First Submitted: January 18, 2024
• First Posted: January 26, 2024
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): September 1, 2028
• Last Updated: March 11, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share