Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
CAEL-101 · 3 trials · 1 indication
Time to all-cause mortality was defined as the number of weeks from the date of randomization to the date of death if it is on or before the end of PETP. Participants alive at the end of PETP (LPI+18 months) were censored at their last known alive date recorded within the PETP. CVHs were events adjudicated and confirmed as such by the Clinical Event Adjudication Committee (CEAC). Hypothesis testing with the Finkelstein-Schoenfeld test and treatment effect estimation with the win-ratio method based on pairwise comparisons of participant outcomes with comparisons performed in a hierarchical manner. To calculate win ratio, participant outcomes based on time to all-cause mortality were first compared and if there was no 'winner' due to censoring then a comparison based on frequency of cardiovascular hospitalization was made. A win ratio \>1 represents a more favorable outcome for CAEL-101 over placebo.
An adverse event (AE) was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, at any dose, that was not necessarily related to the treatment. A TEAE was an AE with an occurrence defined as follows: last study intervention day-first study intervention day + 140 days. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
An adverse event (AE) was as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An SAE was an AE that met at least 1 of the following criteria: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization for the AE, resulted in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, congenital anomaly/birth defect (in the child of a participant who was exposed to the study drug), or an important medical event or reaction. A TEAE was defined as an AE that started after the first dose of treatment and before the last dose of study drug +140 days. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
A DLT was defined as any Grade 3 or greater study intervention-related AE that was clinically significant.
| Arm | Type | Description |
|---|---|---|
| CAEL-101 combined with SoC plasma cell dyscrasia | EXPERIMENTAL | The study is divided into 2 parts, the Primary Study and the Open-Label Extension Study. CAEL-101 is administered as an intravenous (IV) infusion over approximately 2 hours. It is planned that all patients will continue their double-blind treatment until the last patient is randomized in the study plus 18 months. |
| Placebo combined with SoC plasma cell dyscrasia | PLACEBO_COMPARATOR | Patients randomized to receive placebo will receive 0.9% normal saline in an equivalent volume to a CAEL-101 infusion (approximately 250 cc). It is planned that all patients will continue their double-blind treatment until the last patient is randomized in the study plus 18 months. |
| Part A: CAEL-101 combined with SoC CyBorD | EXPERIMENTAL | CAEL-101 is administered as an intravenous (IV) infusion over approximately 2 hours. The initial cohort dose assignments of CAEL-101 will be: Cohort 1 - 500 mg/m\^2 Cohort 2 - 750 mg/m\^2 Cohort 3 - 1000 mg/m\^2. CAEL-101 will be administered weekly for the first 4 weeks, and then every other week until end of study, in combination with the SoC CyBorD chemotherapy. Patients will be treated until death, unacceptable toxicity, symptomatic deterioration, Investigator decision, patient decision or Sponsor decision to terminate the study. Patients from Part A who are in the Continued Treatment Period and who, in the Investigator's judgment, should have their SoC treatment complemented with daratumumab may do so (Part B). |
| Part B: CAEL-101 combined with SoC CyBorD and daratumumab | EXPERIMENTAL | CAEL-101 is administered as an intravenous (IV) infusion at the RP3D dose level. CAEL-101 will be administered weekly for the first 4 weeks, and then every other week until end of study, in combination with the SoC CyBorD chemotherapy and daratumumab. 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. Patients will be treated until death, unacceptable toxicity, symptomatic deterioration, Investigator decision, patient decision or Sponsor decision to terminate the study. |
| Name | Type | Description |
|---|---|---|
| CAEL-101 | DRUG | 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. |
| Placebo | OTHER | Commercially available 0.9% Normal Saline will be used as the placebo. |
| cyclophosphamide, bortezomib, and dexamethasone (CyBorD) regimen | DRUG | According to institutional standard of care. |
| SoC: cyclophosphamide, bortezomib, and Dexamethasone (CyBorD) | DRUG | According to institutional standard of care. |
| Daratumumab | DRUG | Treatment for AL amyloidosis |
Key Inclusion Criteria: * AL amyloidosis stage IIIa based on the European Modification of the 2004 Standard Mayo Clinic Staging who also have NT-proBNP \> 650 ng/L at the time of Screening * Measurable hematologic disease at Screening as defined by at least one of the following: 1. Involved/unin...
CAEL-101 is an investigational small molecule being developed for the treatment of AL amyloidosis, a rare disease. It is currently in Phase 3 clinical trials. The drug is being studied in patients with Mayo Stage IIIa and IIIb AL amyloidosis to evaluate its efficacy and safety.
CAEL-101 is being developed by AstraZeneca PLC, a biopharmaceutical company traded on the stock exchange under the ticker AZN. The company is conducting clinical trials to evaluate the drug's safety and efficacy in patients with AL amyloidosis.
CAEL-101 is currently in Phase 3 clinical development. It is being studied in two Phase 3 trials, both of which are active but not recruiting patients. The drug is investigational and has not been approved by regulatory authorities.
CAEL-101 is being evaluated in two Phase 3 trials: NCT04504825 for Mayo Stage IIIb AL amyloidosis and NCT04512235 for Mayo Stage IIIa AL amyloidosis. Both are randomized, double-blind, placebo-controlled studies. A Phase 2 trial, NCT04304144, has been completed.
CAEL-101 is a small molecule designed to target and remove amyloid deposits in patients with AL amyloidosis. By binding to these deposits, it aims to reduce organ damage caused by the disease. The exact molecular target has not been disclosed.