Clinical Trials /

Phase 1b Study of AEVI-007 in Subjects With Relapsed or Refractory Multiple Myeloma

NCT04671251

Description:

This is a multicenter, open-label, dose-escalation Phase 1b study of AEVI-007 in subjects with relapsed or refractory Multiple Myeloma. The objectives of the study are to evaluate the safety, pharmacokinetics and pharmacodynamics of AEVI-007.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Phase 1b Study of AEVI-007 in Subjects With Relapsed or Refractory Multiple Myeloma
  • Official Title: A Multicenter, Open-Label, Dose-Escalation Phase 1b Study of AEVI-007 in Subjects With Relapsed or Refractory Multiple Myeloma

Clinical Trial IDs

  • ORG STUDY ID: AEVI-007-MM-101
  • NCT ID: NCT04671251

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
AEVI-007AEVI-007

Purpose

This is a multicenter, open-label, dose-escalation Phase 1b study of AEVI-007 in subjects with relapsed or refractory Multiple Myeloma. The objectives of the study are to evaluate the safety, pharmacokinetics and pharmacodynamics of AEVI-007.

Trial Arms

NameTypeDescriptionInterventions
AEVI-007Experimental
  • AEVI-007

Eligibility Criteria

        Inclusion Criteria:

          1. Subject has active R/R multiple myeloma.

          2. Subject has measurable myeloma based on any of the following:

               -  Serum M-protein > 0.5 g/dL

               -  Urine M-protein > 200 mg/24 hours

               -  Serum free light chains > 10 mg/dL

               -  Measurable plasmacytoma or extramedullary disease

          3. Subject has active myeloma despite prior therapy with a proteasome inhibitor, an
             immunomodulatory agent and an anti-CD38 antibody.

             Note: Subject must not be a candidate for regimens known to provide clinical benefit.

          4. Subject has an Eastern Cooperative Oncology Group performance status (ECOG PS) score
             of 0 or 1.

          5. Subject is > 18 years of age.

          6. Subject has adequate hematopoietic, renal and hepatic function, defined as:

               -  Absolute neutrophil count > 1,000/μL; platelet count > 75,000/μL in patients with
                  < 50% marrow involvement

               -  Absolute neutrophil count > 750/μL; platelet count > 50,000/μL in patients with
                  >50% marrow involvement

               -  Serum creatinine < 2.5 mg/dL or calculated creatinine clearance of > 30 mL/min
                  according to the Cockcroft-Gault equation

               -  Aspartate transaminase/alanine transaminase ≤2.5× the upper limit of normal (ULN)
                  and total bilirubin < 2× the ULN

          7. If applicable, the subject has undergone prior autologous hematopoietic stem cell
             transplantation more than 100 days prior to the Screening Visit.

          8. Female patients of childbearing potential who are heterosexually active and male
             patients with female sexual partners of childbearing potential must agree to use an
             effective method of contraception (eg, oral contraceptives, double-barrier methods
             such as a condom and a diaphragm, intrauterine device) or abstain from sexual activity
             during the study and for 220 days (5 half-lives) following the last dose of study
             medication, or to abstain from sexual intercourse for this duration of study
             participation. A woman not of childbearing potential is one who has undergone
             bilateral oophorectomies or who is post-menopausal, defined as the absence of
             menstrual periods for 12 consecutive months.

          9. Subject has provided written informed consent for this study.

        Exclusion Criteria:

          1. Subject has currently active infection requiring use of systemic antimicrobial
             therapy.

          2. Subject has received corticosteroids (>10 mg/daily prednisone or equivalent) or
             chemotherapy within 2 weeks of study drugs (4 weeks for nitrosourea, melphalan or
             monoclonal antibodies).

          3. Subject has hyperviscosity syndrome.

          4. Subject has central nervous system involvement by myeloma, including leptomeningeal
             involvement.

          5. Subject is judged to be at risk for impending fracture.

          6. Subject has known amyloidosis or POEMS (Polyneuropathy, Organomegaly, Endocrinopathy,
             Monoclonal protein, Skin changes) syndrome.

          7. Subject had another malignancy within 1 year of study entry with high probability of
             recurrence.

          8. Subject is pregnant or lactating.

          9. Subject has a history of, or tests positive for, hepatitis B, untreated hepatitis C or
             human immunodeficiency virus (HIV). Subject with hepatitis C who has received a full
             course of anti-viral therapy or who is currently receiving anti-viral therapy with
             undetectable levels of hepatitis C RNA is eligible for the trial.

         10. Subject has undergone major surgery or trauma within 4 weeks of study entry.

         11. Subject has been previously treated with an anti IL 18 antibody.

         12. Subject is currently taking immunomodulatory drugs, including pharmacologic doses of
             systemic glucocorticoids (> 10 mg prednisone daily or equivalent), anti tumor necrosis
             factor alpha (TNFα) antibodies, anti-IL-17 antibodies, anti IL 12/23 antibodies,
             phosphodiesterase-4 (PDE-4) inhibitors, janus kinase (JAK) inhibitors, IL-6
             inhibitors, rituximab, methotrexate, cyclosporine, mycophenolate.

         13. Subject with known active autoimmune disorders including, but not limited to,
             rheumatoid arthritis, lupus, systemic sclerosis, Sjogren's syndrome, psoriatic
             arthritis, ulcerative colitis, Crohn's disease, vasculitis, multiple sclerosis.
             Subjects with autoimmune endocrinopathies on stable doses of replacement hormone
             therapy are eligible for the trial.

         14. Subject has had a prior allogeneic transplant.

         15. Subject has New York Heart Association (NYHA) Class III or IV Congestive Heart Failure
             (CHF), myocardial infarction or acute coronary syndrome within 6 months prior to the
             Screening Visit, ongoing angina pectoris, severe peripheral vascular disease, or any
             other concomitant medical disorder that might interfere with the subject's
             participation in the trial or interpretation of the study data.

         16. Subject has psychiatric, substance abuse or social conditions that would interfere
             with the subject's participation or cooperation with the requirements of the trial.

         17. Subject has known hypersensitivity to any of the components of AEVI-007.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Recommended Phase 2 Dose
Time Frame:Cohorts 1-3 will take approximately 4-5 months
Safety Issue:
Description:Identify the recommended Phase 2 dose based on safety, pharmacokinetics and pharmacodynamics observed in this Phase 1b study.

Secondary Outcome Measures

Measure:Incidence of Treatment Emergent Adverse Events (TEAEs)
Time Frame:Approximately 9 months
Safety Issue:
Description:
Measure:Incidence of Clinically Significant Changes in Clinical Laboratory Results
Time Frame:Approximately 9 months
Safety Issue:
Description:
Measure:Incidence of Clinically Significant Changes in Vital Signs
Time Frame:Approximately 9 months
Safety Issue:
Description:
Measure:Incidence of Clinically Significant Changes in Electrocardiogram Recordings
Time Frame:Approximately 9 months
Safety Issue:
Description:
Measure:Incidence of Clinically Significant Changes to Eastern Cooperative Oncology Group Performance Status (ECOG PS) Score
Time Frame:Approximately 9 months
Safety Issue:
Description:
Measure:Incidence of Clinically Significant Changes in Physical Examination Findings
Time Frame:Approximately 9 months
Safety Issue:
Description:
Measure:Maximum Observed Concentration of AEVI-007
Time Frame:Approximately 9 months
Safety Issue:
Description:
Measure:Apparent Terminal Half-Life of AEVI-007
Time Frame:Approximately 9 months
Safety Issue:
Description:
Measure:Clearance of AEVI-007
Time Frame:Approximately 9 months
Safety Issue:
Description:
Measure:Volume of Distribution of AEVI-007
Time Frame:Approximately 9 months
Safety Issue:
Description:
Measure:Area Under the Concentration-Time Curve From Time 0 to Time t of AEVI-007
Time Frame:Approximately 9 months
Safety Issue:
Description:
Measure:Anti-myeloma activity
Time Frame:Approximately 9 months
Safety Issue:
Description:To assess the anti-myeloma activity of AEVI-007 based on International Myeloma Working Group (IMWG) criteria for response
Measure:Determination of ADAs
Time Frame:Approximately 9 months
Safety Issue:
Description:To determine the incidence of anti-drug antibodies to AEVI-007.
Measure:Time to Response (TTR)
Time Frame:Approximately 9 months
Safety Issue:
Description:Defined as the time from start of the treatment to the first observation of PR or better. TTR is restricted to only subjects with confirmed responses.
Measure:Progression Free Survival (PFS)
Time Frame:Approximately 9 months
Safety Issue:
Description:Defined as the duration from start of the treatment to disease progression or death (regardless of cause of death), whichever comes first
Measure:Duration of Response
Time Frame:Approximately 9 months
Safety Issue:
Description:Defined as the duration from the first observation of PR to the time of disease progression, with deaths from causes other than progression censored

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Aevi Genomic Medicine, LLC, a Cerecor company

Last Updated

December 19, 2020