NCT04304144

A Study to Evaluate the Safety and Tolerability of CAEL-101 in Patients With AL Amyloidosis

CAEL101-203: A Phase 2, Open-label, Multicenter Dose Selection Study to Evaluate the Safety and Tolerability of CAEL-101 in Patients With AL Amyloidosis

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 25 (actual)
• Sponsor: Alexion Pharmaceuticals, Inc. · Industry
• Sex: All
• Age: —
• Healthy volunteers: Not accepted

Summary

AL amyloidosis begins in the bone marrow where abnormal proteins misfold and create free light chains that cannot be broken down. These free light chains bind together to form amyloid fibrils that build up in the extracellular space of organs, affecting the kidneys, heart, liver, spleen, nervous system and digestive tract. The primary purpose of this study is to determine the recommended dose of CAEL-101 to facilitate progression of further clinical trials and evaluate safety and tolerability of CAEL-101 in combination with the standard of care (SoC) cyclophosphamide-bortezomib-dexamethasone (CyBorD) chemotherapy and daratumumab .

Detailed description

This is a multicenter, open-label, sequential cohort, dose-selection study of CAEL-101 in Mayo Stage I, Stage II and Stage IIIa AL amyloidosis patients. CAEL-101 will be administered in combination with the standard of care (SoC) cyclophosphamide-bortezomib-dexamethasone (CyBorD) chemotherapy and daratumumab. The study is divided into two parts with the following objectives: * Part A defines the safety and tolerability of CAEL-101 in combination with SoC CyBorD and determines the recommended Phase 3 dose (RP3D) of CAEL-101 * Part B evaluates the safety and tolerability of CAEL-101 in combination with SoC CyBorD and daratumumab The study will also evaluate the pharmacokinetic profile of CAEL-101 and explore the PK profile of CAEL-101 when given bi-weekly (q2wk) versus once-monthly (q4wk) after the first 50 weeks. Part A of the study will employ a 3+3 dose escalation design. At least 3 patients will be enrolled in each dose cohort unless adverse events (AE) preventing further dosing are observed. CAEL-101 will be administered in combination with the SoC CyBorD chemotherapy. In Part B, a minimum of 6 new patients will receive CAEL-101 administered in combination with SoC CyBorD and daratumumab. Patients from both Parts A and B will receive CAEL-101 therapy weekly and SoC throughout the safety observation period. CAEL-101 study drug infusions will continue, with dosing approximately every two weeks (q2wk) thereafter. SoC will continue per the Investigator's discretion. After completing approximately 50 weeks of treatment, participants may switch to an alternative maintenance dosing regimen of every four weeks (q4wk), if agreed upon by the Investigator and the Sponsor Medical Monitor. Approximately 25 patients will be enrolled in the study at approximately 3 investigator sites. Patients will be treated with CAEL-101 until death, unacceptable toxicity, symptomatic deterioration, Investigator decision, patient decision or Sponsor decision to terminate the study.

Conditions

• AL Amyloidosis

Interventions

Type	Name	Description
DRUG	CAEL-101	The investigational product, CAEL-101, is formulated as a sterile liquid solution of protein plus excipients for dilution in a single-use, stoppered, glass vial. Each 10 mL vial contains 300 mg of CAEL-101 at a concentration of 30 mg/mL. CAEL-101 will be diluted with commercially available 0.9% Normal Saline.
DRUG	SoC: cyclophosphamide, bortezomib, and Dexamethasone (CyBorD)	According to institutional standard of care.
DRUG	Daratumumab	Treatment for AL amyloidosis

Timeline

• Start date: 2020-03-18
• Primary completion: 2023-11-14
• Completion: 2023-11-14
• First posted: 2020-03-11
• Last updated: 2025-03-05
• Results posted: 2025-03-05

Locations

3 sites across 1 country: United States

Regulatory

• FDA-regulated drug study