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

Phase 1

Completed

• Conditions: Refractory Multiple Myeloma; Relapsed Multiple Myeloma
• Interventions: Drug: ION251

• Registration Number: NCT04398485
• Lead Sponsor: Ionis Pharmaceuticals, Inc.

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 Timeline

• Study First Submitted: 2020-05-11
• Study First Submitted QC: 2020-05-18
• Study First Posted: 2020-05-21
• Study Start: 2021-01-20
• Primary Completion: 2024-09-30
• Study Completion: 2024-09-30
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-30
• Last Update Posted: 2024-10-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 23

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
ION251	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.

Primary Outcome Measures

Name	Time	Method
Maximum-Tolerated Dose (MTD)	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)	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

Secondary Outcome Measures

Name	Time	Method
Trough Concentration of ION251	From Baseline up to 28 days from the last dose of study drug
Safety and Tolerability as Measured by the Incidence of TEAEs	Up to 28 days from the last dose of study drug
Incidence of Abnormal Laboratory Values and Vital Signs	Up to 28 days from the last dose of study drug
Cmax: Maximum Observed Concentration ION251	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	From Baseline up to 28 days from the last dose of study drug
t1/2: Distribution Half-life of ION251	From Baseline up to 28 days from the last dose of study drug
Urine 0-24 Hour (hr) Excretion of ION251	Up to 12 months from the last dose of study drug

Trial Locations

Locations (6)

Cedars-Sinai Medical Center; 🇺🇸 Los Angeles, California, United States

Barbara Ann Karmanos Cancer Institute; 🇺🇸 Detroit, Michigan, United States

University of California San Diego Moores Cancer Center; 🇺🇸 La Jolla, California, United States

Washington University School of Medicine in Saint Louis; 🇺🇸 Saint Louis, Missouri, United States

Levine Cancer Institute; 🇺🇸 Charlotte, North Carolina, United States

UCLA Rrmc; 🇺🇸 Los Angeles, California, United States