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A Study of ION251 Administered to Patients With Relapsed/Refractory Multiple Myeloma

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ClinicalTrials.gov Identifier: NCT04398485
Recruitment Status : Recruiting
First Posted : May 21, 2020
Last Update Posted : June 18, 2021
Sponsor:
Information provided by (Responsible Party):
Ionis Pharmaceuticals, Inc.

Tracking Information
First Submitted Date  ICMJE May 11, 2020
First Posted Date  ICMJE May 21, 2020
Last Update Posted Date June 18, 2021
Actual Study Start Date  ICMJE January 20, 2021
Estimated Primary Completion Date January 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 18, 2020)
  • Maximum-Tolerated Dose (MTD) [ Time Frame: Up to 28 days from the last dose of study drug in Cycle 1 (each cycle is 28 days) ]
    MTD is defined as the maximum dose at which ≤ 1 of 3 evaluable participants experiences a dose-limiting toxicity (DLT) within Cycle 1 and there are 2 of 3 or 2 of 6 evaluable participants in the next higher-dose level experiencing a DLT within Cycle 1. If no dose in the dose-escalation has 2 of 3 or 2 of 6 evaluable participants experiencing a DLT, the highest dose level is considered the MTD
  • Recommended Phase 2 Dose (PR2D) [ Time Frame: Up to 28 days from the last dose of study drug ]
    RP2D is chosen based on the dose response and exposure-response analyses of the pooled clinical PK, PD, safety results, and anti-myeloma activity from both Part 1 and Part 2
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 18, 2020)
  • Safety and Tolerability as Measured by the Incidence of TEAEs [ Time Frame: Up to 28 days from the last dose of study drug ]
  • Incidence of Abnormal Laboratory Values and Vital Signs [ Time Frame: Up to 28 days from the last dose of study drug ]
  • Cmax: Maximum Observed Concentration ION251 [ Time Frame: From Baseline up to 28 days from the last dose of study drug ]
  • AUC[0-t]: Area Under the Plasma Concentration-Time Curve from Hour zero to t of ION251 [ Time Frame: From Baseline up to 28 days from the last dose of study drug ]
  • t1/2: Distribution Half-life of ION251 [ Time Frame: From Baseline up to 28 days from the last dose of study drug ]
  • Trough Concentration of ION251 [ Time Frame: From Baseline up to 28 days from the last dose of study drug ]
  • Urine 0-24 Hour (hr) Excretion of ION251 [ Time Frame: Up to 12 months from the last dose of study drug ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of ION251 Administered to Patients With Relapsed/Refractory Multiple Myeloma
Official Title  ICMJE A Phase 1 Study of ION251 Administered by Intravenous Infusion to Patients With Relapsed/Refractory Multiple Myeloma
Brief Summary The purpose of this study is to determine the maximum-tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of ION251 in patients with relapsed/refractory multiple myeloma.
Detailed Description This is a two-part, multi-center first in human study of ION251 in up to 80 participants. Part 1 will use a 3+3 dose-escalation scheme in sequential cohorts to determine the MTD and RP2D during repeated 28-day treatment cycles. MTD will be determined by the number of participants with AEs meeting the dose-limiting toxicity (DLT) criteria during Cycle 1. The MTD determined in Part 1 will be used with other variables to inform a RP2D for participants proceeding to Part 2 for further assessments in the safety, tolerability and anti-myeloma activity.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Relapsed Multiple Myeloma
  • Refractory Multiple Myeloma
Intervention  ICMJE Drug: ION251
ION251 administered by IV infusion
Study Arms  ICMJE Experimental: ION251
In Part 1, the dose escalation phase, increased amounts of ION251 will be administered at multiple time points by intravenous (IV) infusion during 28-day cycles. In Part 2, the determined RP2D of ION251 will be administered at multiple time points by IV infusion.
Intervention: Drug: ION251
Publications * Mondala PK, Vora AA, Zhou T, Lazzari E, Ladel L, Luo X, Kim Y, Costello C, MacLeod AR, Jamieson CHM, Crews LA. Selective antisense oligonucleotide inhibition of human IRF4 prevents malignant myeloma regeneration via cell cycle disruption. Cell Stem Cell. 2021 Apr 1;28(4):623-636.e9. doi: 10.1016/j.stem.2020.12.017. Epub 2021 Jan 20.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 18, 2020)
80
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 2024
Estimated Primary Completion Date January 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Aged ≥ 18 years at the time of informed consent
  2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  3. Measurable multiple myeloma (MM)
  4. In need of systemic treatment for MM and either is refractory to or has failed treatment with, is intolerant to or has refused, or is not otherwise a candidate in the opinion of the Investigator, for any of the currently available established therapies known to provide clinical benefit in relapsed/refractory MM. Refractory to treatment is defined as documented MM disease progression while on or within 60 days from the last dose (LD) of treatment

Exclusion Criteria:

  1. Screen laboratory results as follows, or any other clinically significant abnormalities in screen laboratory values that would render a participant unsuitable for inclusion

    • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2 × upper limit of normal (ULN)
    • Total bilirubin > 1.3 × ULN
    • Absolute neutrophil count ≤ 1.0 1000/cubic millimeter (k/mm^3)
    • Platelet count < 50 k/mm^3
    • Hemoglobin < 8.0 g/dL
    • Estimated glomerular filtration rate (eGFR) < 50 milliliters per minute (mL/min)/1.73 square meter (m^2)
    • Urine albumin creatinine ratio > 100 mg/g
  2. History of or current plasma cell leukemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, and skin changes) syndrome, solitary bone or extramedullary plasmacytoma as the only evidence for plasma cell dyscrasia, myelodysplastic syndrome or a myeloproliferative neoplasm
  3. Uncontrolled hypertension (systolic pressure ≥ 160 mm of mercury (mm Hg) and/or diastolic pressure ≥ 100 mm Hg)
  4. Presence of a bleeding disorder or an underlying disease state associated with active bleeding.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Ionis Pharmaceuticals 800-679-4747 patients@ionisph.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04398485
Other Study ID Numbers  ICMJE ION251-CS1
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Ionis Pharmaceuticals, Inc.
Study Sponsor  ICMJE Ionis Pharmaceuticals, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Ionis Pharmaceuticals, Inc.
Verification Date June 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP