Study of NM8074 in Patients With aHUS With Evidence of Ongoing Thrombotic Microangiopathy

NCT05684159 | Not Yet Recruiting Phase 2 FDA Drug

• 1 other identifier: NM8074-aHUS-401
• Study Type: interventional
• Target: 12
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a Phase II, open-label study designed to determine if intravenously administered NM8074 results in remission from TMA in treatment-naïve aHUS patients.

Conditions

aHUS - Atypical Hemolytic Uremic Syndrome

Outcome Measures

Primary Outcomes (7)

• Normalization of platelet count (≥150 x 10^9/L)

  Up to Study Day 120

• Normalization of LDH levels to below ULN

  Up to Study Day 120

• Normalization of Schistocyte levels (<1%)

  Up to Study Day 120

• Change from Baseline or Percent Change from Baseline in renal function

  Assessed via the change from baseline or percent change from baseline in serum creatinine level.

  Up to Study Day 120

• Change from Baseline or Percent Change from Baseline in Haptoglobin

  Up to Study Day 120

• Change from Baseline or Percent Change from Baseline in Hemoglobin

  Up to Study Day 120

• Change from Baseline or Percent Change from Baseline in proteinuria/creatininuria

  Up to Study Day 120

Secondary Outcomes (8)

• Time to achieve complete TMA response

  Baseline through Study Day 120

• Time to achieve higher hemoglobin from baseline

  Baseline through Study Day 120

• Change from Baseline or Percent Change from Baseline in blood clots

  Up to Study Day 120

• Change from Baseline or Percent Change from Baseline in the total number of plasma infusions or exchanges

  Baseline through Study Day 120

• Change from Baseline or Percent Change from Baseline in eGFR (estimated glomerular filtration rate)

  Baseline through Study Day 120

Other Outcomes (6)

• Change from Baseline or Percent Change from Baseline in CP modulation

  Baseline through Study Day 120

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

  Baseline through Study Day 120

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

  Baseline through Study Day 120

Study Arms (2)

Cohort 1

EXPERIMENTAL

6 subjects will receive an intravenous (IV) infusion of NM8074 at every two weeks for a total of 7 doses

Drug: NM8074

Cohort 2

EXPERIMENTAL

6 subjects will receive weekly doses of 10 mg/kg for a total of 4 doses followed by biweekly doses at 20 mg/kg for a total of 5 doses

Drug: NM8074

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. Patients in Cohort 2 will receive weekly doses of 10 mg/kg for a total of 4 doses from Day 1 to Day 22 followed by biweekly doses at 20 mg/kg for a total of 5 doses from Day 29 to Day 85.

Cohort 1; Cohort 2

Eligibility Criteria

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

You may qualify if:

• Patients ≥ 18 years at the time of consent
• Patients with evidence of resistant or relapsed complement-mediated aHUS with symptoms of Thrombocytopenia, hemolysis, ongoing Thrombotic Microangiopathy and acute kidney injury.
• Evidence of ongoing Thrombotic Microangiopathy which includes Haptoglobin \<LLN or undetectable and/or presence of schistocytes
• Acute kidney injury (proteinuria/creatinuria \> ULN and/or reduced eGFR)
• Platelets less than 150,000 per microliter (Thrombocytopenia)
• Anemia (Hemoglobin ≤10 g/dL) due to hemolysis
• Lactate dehydrogenase (LDH) level ≥ 1.5 times the upper limit of normal (xULN) during 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 and MenB meningococcal serogroup B vaccine (Bexsero®). If the window of vaccination is short, then patients will be prophylactically treated with appropriate antibiotics
• Willing and able to understand and complete informed consent procedures, including signing and dating the informed consent form (ICF), and comply with the study visit schedule.
• 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.
• 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 1 month after stopping the investigational drug.

You may not qualify if:

• History of bone marrow, hematopoietic stem cell, or solid organ transplantation
• Treatment with complement blockers
• Patients with infections
• HUS due to ADAMTS-13 deficiency (\<5%)
• Kidney disease other than aHUS
• Chronic dialysis (hemo or peritoneal)
• Liver disease or other major autoimmune diseases
• Typical HUS (Shiga toxin +)
• Known Systemic Lupus Erythematosus (SLE), Systemic Sclerosis, or antiphospholipid antibody positivity or syndrome
• History of currently active primary or secondary immunodeficiency
• Currently active systemic infection or suspicion of active bacterial, viral, or fungal infection within 2 weeks prior to first dose, or history of unexplained, recurrent bacterial infections
• Has a currently active or known history of meningococcal disease or N. meningitidis infection
• Severe concurrent co-morbidities not amenable to active treatment, e.g., patients with severe kidney disease (CKD stage 4, chronic dialysis)
• Females who have a positive pregnancy test result at Screening or on Day 1.
• Pregnant, planning to become pregnant, or nursing female subjects.

Sponsors & Collaborators

• NovelMed Therapeutics: lead

Related Publications (4)

• Barbour T, Scully M, Ariceta G, Cataland S, Garlo K, Heyne N, Luque Y, Menne J, Miyakawa Y, Yoon SS, Kavanagh D; 311 Study Group Members. Long-Term Efficacy and Safety of the Long-Acting Complement C5 Inhibitor Ravulizumab for the Treatment of Atypical Hemolytic Uremic Syndrome in Adults. Kidney Int Rep. 2021 Mar 24;6(6):1603-1613. doi: 10.1016/j.ekir.2021.03.884. eCollection 2021 Jun.

  PMID: 34169200 BACKGROUND

• Cammett TJ, Garlo K, Millman EE, Rice K, Toste CM, Faas SJ. Exploratory Prognostic Biomarkers of Complement-Mediated Thrombotic Microangiopathy (CM-TMA) in Adults with Atypical Hemolytic Uremic Syndrome (aHUS): Analysis of a Phase III Study of Ravulizumab. Mol Diagn Ther. 2023 Jan;27(1):61-74. doi: 10.1007/s40291-022-00620-3. Epub 2022 Nov 4.

  PMID: 36329366 BACKGROUND

• Cofiell R, Kukreja A, Bedard K, Yan Y, Mickle AP, Ogawa M, Bedrosian CL, Faas SJ. Eculizumab reduces complement activation, inflammation, endothelial damage, thrombosis, and renal injury markers in aHUS. Blood. 2015 May 21;125(21):3253-62. doi: 10.1182/blood-2014-09-600411. Epub 2015 Apr 1.

  PMID: 25833956 BACKGROUND

• Pugh D, O'Sullivan ED, Duthie FA, Masson P, Kavanagh D. Interventions for atypical haemolytic uraemic syndrome. Cochrane Database Syst Rev. 2021 Mar 23;3(3):CD012862. doi: 10.1002/14651858.CD012862.pub2.

  PMID: 33783815 BACKGROUND

MeSH Terms

Conditions

Atypical Hemolytic Uremic Syndrome

Condition Hierarchy (Ancestors)

Hemolytic-Uremic Syndrome; Uremia; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Thrombotic Microangiopathies; Thrombocytopenia; Blood Platelet Disorders; Cytopenia

Central Study Contacts

Rekha Bansal, PhD

CONTACT

2164402696; clinicalsae@novelmed.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study will enroll a planned total of 12 patients as subjects for the trial, with extra enrollment if needed, at the discretion of the Investigator. All subjects will be assigned to either Cohort 1 or Cohort 2. Enrollment in Cohort 2 will occur after at least three patients in Cohort 1 have been evaluated for safety for 3 days after the first dose. No more than three patients will be dosed in a day. Safety data will be assessed and reviewed by the Sponsor and Study Investigators for dosed subjects prior to dosing of the rest of the study subjects. In Cohort 1, all 6 subjects will be administered 20 mg/kg of NM8074 intravenously every two weeks for a total of 7 doses. All 6 patients in Cohort 2 will receive weekly doses of 10 mg/kg for a total of 4 doses followed by biweekly doses at 20 mg/kg for a total of 5 doses.

Study Record Dates

• First Submitted: January 4, 2023
• First Posted: January 13, 2023
• Study Start (Estimated): November 1, 2027
• Primary Completion (Estimated): April 1, 2030
• Study Completion (Estimated): February 1, 2031
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share