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AL (or light chain) 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 whether CAEL-101, a monoclonal antibody that removes AL amyloid deposits from tissues and organs, improves overall survival, reduces cardiovascular related hospitalizations and it is safe and well tolerated in patients with stage IIIb AL amyloidosis.
This is a double-blind, randomized, multicenter international Phase 3 study of CAEL-101 combined with standard of care (SoC) plasma cell dyscrasia (PCD) treatment versus placebo combined with SoC PCD treatment in Mayo stage IIIb PCD treatment-naïve AL amyloidosis patients. The primary evaluation treatment period (PETP) part of the study will stop when the last patient is randomized in the PETP plus 18 months. Approximately 124 patients will be enrolled using a 2:1 randomization ratio. Stratification will be based on geographic region across investigator sites. The primary endpoint is a composite endpoint of all-cause mortality and frequency of cardiovascular hospitalizations. Patients in both study intervention groups will be followed from randomization until death from any cause, heart transplant, left wall assist device (LVAD) implantation or until the end of study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| CAEL-101 combined with SoC plasma cell dyscrasia | Experimental | 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. The study is divided into 2 parts, the Primary Evaluation Treatment period part and the Open-Label Extension period of Study. |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| A Hierarchical Combination of Time to All-cause Mortality and Frequency of Cardiovascular Hospitalizations (CVHs) Analyzed by Win Ratio | 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. | Day 1 through end of the participant's PETP (Participants were enrolled on a rolling basis. Therefore, the primary analysis for the study was conducted 18-47 months after the study randomization.) |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 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. | Day 1 through end of the participant's PETP (Participants were enrolled on a rolling basis. Therefore, the primary analysis for the study was conducted 18-47 months after the study randomization.) |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in the Kansas City Cardiomyopathy Questionnaire-Overall Score (KCCQ-OS) | The KCCQ-OS is a 23-item self-administered questionnaire that quantifies physical function, symptoms, social function, self-efficacy and knowledge and quality of life. It uses an ordinal, adjectival (Likert) scale. Participants provide their level of agreement or disagreement with an agree-disagree scale for a series of statements. The questionnaire captures how the participants feel physically. The overall score was calculated as the sum from all 23 items and ranges from 0 to 100, where higher scores reflected better health status (fewer symptoms, fewer social or physical limitations, and better quality of life). |
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Key Inclusion Criteria:
AL amyloidosis stage IIIb based on the European Modification of the 2004 Standard Mayo Clinic Staging (NT-proBNP > 8,500 ng/L) at the time of Screening
Measurable hematologic disease at Screening as defined by at least one of the following:
Histopathological diagnosis of amyloidosis based on polarizing light microscopy of green bi-refringent material in Congo red stained tissue specimens AND confirmation of AL derived amyloid deposits by at least one of the following:
Cardiac involvement as defined by:
i. Endomyocardial biopsy demonstrating AL cardiac amyloidosis or ii. Echocardiogram demonstrating a mean left ventricular wall thickness (calculated as [IVSd+LPWd]/2) of > 12 mm at diastole in the absence of other causes (e.g., severe hypertension, aortic stenosis), which would adequately explain the degree of wall thickening or iii. Cardiac magnetic resonance imaging (MRI) with gadolinium contrast agent diagnostic of cardiac amyloidosis
Planned first-line treatment for plasma cell dyscrasia is cyclophosphamide-bortezomib-dexamethasone (CyBorD)-based regimen administered as SoC
Women of childbearing potential (WOCBP) must have a negative pregnancy test during Screening and must agree to use highly effective contraception from Screening to at least 5 months following the last study drug administration or 12 months following the last dose of her PCD therapy, whichever is longer
Men must be surgically sterile or must agree to use highly effective contraception and refrain from donating sperm from Screening to at least 5 months following the last study drug administration or 12 months following the last dose of their PCD therapy, whichever is longer
Key Exclusion Criteria:
Have any other form of amyloidosis other than AL amyloidosis
Received prior therapy for AL amyloidosis or multiple myeloma. A maximum exposure of 2 weeks of a CyBorD-based PCD treatment after Screening laboratory samples are obtained and prior to randomization is allowed
Has POEMS (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes) syndrome or multiple myeloma defined as clonal bone marrow plasma cells > 10% from a bone marrow biopsy (performed ≤ 3 months prior to signing the ICF) or biopsy-proven (performed ≤ 3 months prior to signing the ICF) bony or extramedullary plasmacytoma AND one or more of the following CRAB features:
a. Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder (e.g., multiple myeloma and POEMS syndrome), specifically: i. Hypercalcemia: serum calcium > 0.25 mmol/L (> 1 mg/dL) higher than the ULN or > 2.75 mmol/L (> 11 mg/dL) OR ii. Renal insufficiency: creatinine clearance < 40 mL per minute or serum creatinine > 177 mol/L (> 2 mg/dL) OR iii. Anemia: hemoglobin value of > 20 g/L below the lowest limit of normal, or a hemoglobin value < 100 g/L OR iv. Bone lesions: one or more osteolytic lesion on imaging tests (performed ≤ 3 months prior to signing the ICF): skeletal radiography, CT, or PET/CT, or MRI. If bone marrow has < 10% clonal plasma cells, more than one bone lesion is required to distinguish from solitary plasmacytoma with minimal marrow involvement OR b. Any one of the following biomarkers of malignancy: i. 60% or greater clonal plasma cells on bone marrow examination OR ii. More than one focal lesion on MRI that is at least 5mm or greater in size
Have supine systolic blood pressure < 90 mmHg or symptomatic orthostatic hypotension, defined as a decrease in systolic blood pressure upon standing of > 30 mmHg despite medical management (e.g., midodrine, fludrocortisones) in the absence of volume depletion
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| Name | Affiliation | Role |
|---|---|---|
| Scott Swenson, MD | Alexion, AstraZeneca Rare Disease | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Duarte | California | 91010 | United States | ||
| Research Site |
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| Label | URL |
|---|---|
| CSR Synopsis - Redacted | View source |
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Each patient will be assigned a unique identifier after signing the Informed Consent Form (ICF). Patient numbers will not be reassigned. Any patient records or datasets transferred to the Sponsor must contain only the unique identifier and must not include patient names or any information which would make the patient identifiable. Patients will be informed that their personal study-related data will be used by the Sponsor in accordance with local data protection laws and that their medical records may be examined by representatives of the Sponsor, Institutional Review Board (IRB)/Independent Ethics Committee (IEC) members and by inspectors from regulatory authorities. Study monitors will inspect all documents and records that are required to be maintained by the Investigator for this study.
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Subgroup analyses reported for 2 free light chain (FLC) isotypes (Kappa, Lambda) as following subgroups, 'Kappa FLC Subtype' and 'Lambda FLC Subtype'. The sum of the participants for the "CAEL-101 + Plasma Cell Dyscrasia Treatment" Arm/Group in the "Kappa FLC Subtype" and "Lambda FLC Subtype" Rows (25+57=82) appears inconsistent with the number of participants specified in the "Received at Least 1 Dose of Study Drug" Row (84) due to 2 participants were not classified as either kappa or lambda
This study consisted of 2 periods: the Primary Evaluation Treatment Period (PETP) and the Open-label Extension Period (OLEP). Primary analysis data reported based only on data collected through the end of the participant's PETP (last participant in [LPI] plus 18 months). Final data will be reported after study completion.
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| ID | Title | Description |
|---|---|---|
| FG000 | CAEL-101 + Plasma Cell Dyscrasia Treatment | During the PETP, participants were administered CAEL-101 as an intravenous (IV) infusion over approximately 2 hours, in addition to standard-of-care (SoC) plasma cell dyscrasia treatment. All participants continued their double-blind treatment until LPI+18 months. All participants had the option to enter into the OLEP, where they continued to receive CAEL-101 in addition to any SoC prescribed by a physician. |
| Title | Milestones | Reasons Not Completed | ||||
|---|---|---|---|---|---|---|
| PETP |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jun 26, 2024 | May 8, 2026 |
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This is a double-blind, randomized, multicenter, international Phase 3 study of CAEL-101 combined with SoC PCD treatment versus placebo combined with SoC PCD treatment in Mayo stage IIIb PCD treatment-naïve AL amyloidosis patients.
Approximately 124 patients will be enrolled using a 2:1 randomization ratio and stratification will be based on geographic region across investigator sites.
The primary evaluation treatment period (PETP) part of the study will stop when the last patient is randomized in the PETP plus 18 months. Patients in both study intervention groups will be followed from randomization until death from any cause, heart transplant, left valve assist device (LVAD) implantation or until the end of study.
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This is a double-blind, randomized, multicenter international Phase 3 study.
|
| 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. |
|
| Baseline, Week 50 |
| Change From Baseline in Distance Walked During a Six-minute Walk Test (6MWT) | The 6MWT measures the distance a participant can quickly walk on a flat, hard surface in a period of 6 minutes. It evaluates the global and integrated response of all the systems involved during exercise. This is a self-paced test; participants choose their own intensity of exercise and are allowed to stop and rest during the test. | Baseline, Week 50 |
| All-cause Mortality | All-cause mortality was defined as death on or before the end of the PETP. Participants who were alive at the end of the PETP (last participant randomized plus 18 months) were censored at their last known alive date recorded within the PETP. All deaths, regardless of causality or whether they were reported as a reason for study discontinuation, are reported in the All-Cause Mortality section. | Day 1 through end of the participant's PETP (Participants were enrolled on a rolling basis. Therefore, analysis for the study was conducted 18-47 months after the study randomization.) |
| Frequency of CVHs | CVHs were those events that were adjudicated and confirmed as such by the CEAC. Frequency of CEAC-adjudicated CVH was calculated using negative binomial regression analysis with study intervention, study, geographic region, daratumumab usage at Baseline, and offset term equal to log of each participant's follow-up time for cardiovascular hospitalization included in the model. | Day 1 through end of the participant's PETP (Participants were enrolled on a rolling basis. Therefore, analysis for the study was conducted 18-47 months after the study randomization.) |
| Change From Baseline in Global Longitudinal Strain (GLS%) | Change in heart function was measured by GLS%, a noninvasive imaging technique that uses echocardiography to assess heart. GLS% expresses longitudinal shortening as a percentage (change in length as a proportion to baseline length) and is reported as a negative value. A more negative value is usually associated with cardiac enhancement. | Baseline, Week 50 |
| Change From Baseline in the Short Form-36 (SF-36) Version 2 (v2) Physical Component Score (PCS) | The SF-36v2 is a self-administered questionnaire containing 36 items that measure health on functional status, well-being, and overall evaluation of health in 8 domains, including vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, and mental health, using scaled, ordinal responses (for example, All of the time, Most of the time, A good bit of the time). The SF-36v2 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale, with higher scores indicating an increased quality of life. The 8 multi-item scales are aggregated and summed to give the final PCS. The final score ranges from 0-100, with higher scores indicating an increased quality of life. | Baseline, Week 50 |
| Change From Baseline in N-Terminal Pro-B-type Natriuretic Peptide (NT-proBNP) in Blood Samples | For each participant, blood samples were assayed for NT-proBNP, comparing the participant's baseline value over time to assess reduced amyloidosis, as measured by a decrease in NT-proBNP. A decrease indicates cardiac enhancement. Results reported as nanograms/milliliter (ng/mL). | Baseline, Week 50 |
| Palo Alto |
| California |
| 94304 |
| United States |
| Research Site | San Francisco | California | 94143 | United States |
| Research Site | Weston | Florida | 33331 | United States |
| Research Site | Indianapolis | Indiana | 46202 | United States |
| Research Site | New Orleans | Louisiana | 70112 | United States |
| Research Site | Boston | Massachusetts | 02111 | United States |
| Research Site | Boston | Massachusetts | 02118 | United States |
| Research Site | Boston | Massachusetts | 02215 | United States |
| Research Site | Detroit | Michigan | 48201 | United States |
| Research Site | Rochester | Minnesota | 55905 | United States |
| Research Site | St Louis | Missouri | 63110 | United States |
| Research Site | New York | New York | 10032 | United States |
| Research Site | New York | New York | 10065 | United States |
| Research Site | Rochester | New York | 14642 | United States |
| Research Site | Winston-Salem | North Carolina | 27157 | United States |
| Research Site | Cleveland | Ohio | 44195 | United States |
| Research Site | Columbus | Ohio | 43210 | United States |
| Research Site | Portland | Oregon | 97239 | United States |
| Research Site | Philadelphia | Pennsylvania | 19104 | United States |
| Research Site | Nashville | Tennessee | 37232 | United States |
| Research Site | Dallas | Texas | 75390 | United States |
| Research Site | Houston | Texas | 77030 | United States |
| Research Site | Salt Lake City | Utah | 84112 | United States |
| Research Site | Seattle | Washington | 98109 | United States |
| Research Site | Milwaukee | Wisconsin | 53226 | United States |
| Research Site | Box Hill | 3128 | Australia |
| Research Site | Brisbane | 4102 | Australia |
| Research Site | Westmead | 2145 | Australia |
| Research Site | Linz | 4020 | Austria |
| Research Site | Vienna | 1090 | Austria |
| Research Site | Anderlecht | 1070 | Belgium |
| Research Site | Leuven | 3000 | Belgium |
| Research Site | Porto Alegre | 90110-270 | Brazil |
| Research Site | Ribeirão Preto | 14048-900 | Brazil |
| Research Site | Salvador | 41253-190 | Brazil |
| Research Site | São José do Rio Preto | 15090-000 | Brazil |
| Research Site | Calgary | Alberta | T2N 4N2 | Canada |
| Research Site | Edmonton | Alberta | T6G 1Z2 | Canada |
| Research Site | Toronto | Ontario | M5G 2M9 | Canada |
| Research Site | Beijing | 100730 | China |
| Research Site | Guangzhou | 510180 | China |
| Research Site | Hangzhou | 310009 | China |
| Research Site | Wenzhou | 325000 | China |
| Research Site | Wuhan | 430022 | China |
| Research Site | Ostrava - Poruba | 70852 | Czechia |
| Research Site | Prague | 12808 | Czechia |
| Research Site | Caen | 14033 | France |
| Research Site | Créteil | 94000 | France |
| Research Site | Limoges | 87042 | France |
| Research Site | Marseille | 13009 | France |
| Research Site | Paris | 75010 | France |
| Research Site | Pessac | 33604 | France |
| Research Site | Pierre-Bénite | 69310 | France |
| Research Site | Poitiers | 86021 | France |
| Research Site | Rennes | 35033 | France |
| Research Site | Toulouse | 31100 | France |
| Research Site | Tours | 37044 | France |
| Research Site | Berlin | 13353 | Germany |
| Research Site | Düsseldorf | 40225 | Germany |
| Research Site | Essen | 45147 | Germany |
| Research Site | Hamburg | 22767 | Germany |
| Research Site | Heidelberg | 69120 | Germany |
| Research Site | Würzburg | 97080 | Germany |
| Research Site | Athens | 11528 | Greece |
| Research Site | Rio | 26504 | Greece |
| Research Site | Haifa | 31096 | Israel |
| Research Site | Jerusalem | 91120 | Israel |
| Research Site | Tel Litwinsky | 52621 | Israel |
| Research Site | Naples | 80131 | Italy |
| Research Site | Pavia | 27100 | Italy |
| Research Site | Pisa | 56126 | Italy |
| Research Site | Roma | 00128 | Italy |
| Research Site | Fukushima | 960-1295 | Japan |
| Research Site | Nagoya | 467-8602 | Japan |
| Research Site | Shibuya-ku | 150-8935 | Japan |
| Research Site | Groningen | 9713 GZ | Netherlands |
| Research Site | Utrecht | 3508 GA | Netherlands |
| Research Site | Gdansk | 80-214 | Poland |
| Research Site | Poznan | 60-569 | Poland |
| Research Site | Warsaw | 01-748 | Poland |
| Research Site | Seoul | 03080 | South Korea |
| Research Site | Seoul | 06351 | South Korea |
| Research Site | Barcelona | 08036 | Spain |
| Research Site | Barcelona | 8035 | Spain |
| Research Site | Gijón | 33394 | Spain |
| Research Site | Majadahonda | 28222 | Spain |
| Research Site | Pamplona | 31008 | Spain |
| Research Site | Seville | 41013 | Spain |
| Research Site | London | WC1E 6AG | United Kingdom |
| FG001 | Placebo + Plasma Cell Dyscrasia Treatment | During the PETP, participants were administered placebo as an IV infusion over approximately 2 hours, in addition to SoC plasma cell dyscrasia treatment. All participants continued their double-blind treatment until LPI+18 months. All participants had the option to enter into the OLEP, where they continued to receive CAEL-101 in addition to any SoC prescribed by a physician. |
|
| Received at Least 1 Dose of Study Drug | Safety Set: all randomized participants who received at least 1 dose of the study intervention. |
|
| Kappa FLC Subtype | Participants with the Kappa FLC subtype who were randomized and received at least 1 dose of study drug in this subgroup. |
|
| Lambda FLC Subtype | Participants with the Lambda FLC subtype who were randomized and received at least 1 dose of study drug in this subgroup. |
|
| Entered OLEP | Based upon Safety Set: all randomized participants who received at least 1 dose of the study intervention. |
|
| Did Not Enter OLEP | Based upon Safety Set: all randomized participants who received at least 1 dose of the study intervention. |
|
| COMPLETED | Only deaths indicated as leading to study discontinuation are reported in the Participant Flow section. All deaths regardless of causality or whether they were reported as a reason for study discontinuation are reported in the All-Cause Mortality section. |
|
| NOT COMPLETED |
|
|
| OLEP |
|
|
Intent-to-treat Set: all participants who were randomized, presented as 'Overall (All Randomized Participants)' and 2 subgroups, 'Kappa FLC Subtype' and 'Lambda FLC Subtype'.
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| ID | Title | Description |
|---|---|---|
| BG000 | CAEL-101 + Plasma Cell Dyscrasia Treatment | During the PETP, participants were administered CAEL-101 as an IV infusion over approximately 2 hours, in addition to SoC plasma cell dyscrasia treatment. All participants continued their double-blind treatment until LPI+18 months. All participants had the option to enter into the OLEP, where they continued to receive CAEL-101 in addition to any SoC prescribed by a physician. |
| BG001 | Placebo + Plasma Cell Dyscrasia Treatment | During the PETP, participants were administered placebo as an IV infusion over approximately 2 hours, in addition to SoC plasma cell dyscrasia treatment. All participants continued their double-blind treatment until LPI+18 months. All participants had the option to enter into the OLEP, where they continued to receive CAEL-101 in addition to any SoC prescribed by a physician. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Data reported for Overall participants and for 2 FLC subtypes (Kappa and Lambda). | Mean | Standard Deviation | Years |
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| Sex/Gender, Customized | Data reported for Overall participants and for 2 FLC subtypes (Kappa and Lambda). | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Ethnicity Baseline Characteristic | Data reported for Overall participants and for 2 FLC subtypes (Kappa and Lambda). | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Race Baseline Characteristic | Data reported for Overall participants and for 2 FLC subtypes (Kappa and Lambda). | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | A Hierarchical Combination of Time to All-cause Mortality and Frequency of Cardiovascular Hospitalizations (CVHs) Analyzed by Win Ratio | 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. | Intent-to-Treat Set: all participants who were randomized. As prespecified, data collected and reported as 'Overall (All Randomized Participants)' and per subgroups 'Kappa FLC Subtype' and 'Lambda FLC Subtype'. For the win-ratio analysis, comparisons were made between participants in the 'CAEL-101 + Plasma Cell Dyscrasia Treatment' arm and the 'Placebo + Plasma Cell Dyscrasia Treatment' arm of each reporting group. | Posted | Number | 95% Confidence Interval | win ratio | Day 1 through end of the participant's PETP (Participants were enrolled on a rolling basis. Therefore, the primary analysis for the study was conducted 18-47 months after the study randomization.) |
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| Primary | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 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. | Safety Set: all randomized participants who received at least 1 dose of the study intervention. As prespecified, data collected and reported as 'Overall (All Safety Set Participants)' and per subgroups 'Kappa FLC Subtype' and 'Lambda FLC Subtype'. | Posted | Count of Participants | Participants | Day 1 through end of the participant's PETP (Participants were enrolled on a rolling basis. Therefore, the primary analysis for the study was conducted 18-47 months after the study randomization.) |
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| Secondary | Change From Baseline in the Kansas City Cardiomyopathy Questionnaire-Overall Score (KCCQ-OS) | The KCCQ-OS is a 23-item self-administered questionnaire that quantifies physical function, symptoms, social function, self-efficacy and knowledge and quality of life. It uses an ordinal, adjectival (Likert) scale. Participants provide their level of agreement or disagreement with an agree-disagree scale for a series of statements. The questionnaire captures how the participants feel physically. The overall score was calculated as the sum from all 23 items and ranges from 0 to 100, where higher scores reflected better health status (fewer symptoms, fewer social or physical limitations, and better quality of life). | Intent-to-Treat Set: all participants who were randomized. As prespecified, data collected and reported as 'Overall (All Randomized Participants)' and per subgroups 'Kappa FLC Subtype' and 'Lambda FLC Subtype'. Here, 'Overall Number of Participants Analyzed' and 'Number Analyzed' signifies those participants evaluable for this outcome measure. | Posted | Mean | Standard Deviation | score on a scale | Baseline, Week 50 |
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| Secondary | Change From Baseline in Distance Walked During a Six-minute Walk Test (6MWT) | The 6MWT measures the distance a participant can quickly walk on a flat, hard surface in a period of 6 minutes. It evaluates the global and integrated response of all the systems involved during exercise. This is a self-paced test; participants choose their own intensity of exercise and are allowed to stop and rest during the test. | Intent-to-Treat Set: all participants who were randomized. As prespecified, data collected and reported as 'Overall (All Randomized Participants)' and per subgroups 'Kappa FLC Subtype' and 'Lambda FLC Subtype'. Here, 'Overall Number of Participants Analyzed' and 'Number Analyzed' signifies those participants evaluable for this outcome measure. | Posted | Mean | Standard Deviation | meters | Baseline, Week 50 |
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| Secondary | All-cause Mortality | All-cause mortality was defined as death on or before the end of the PETP. Participants who were alive at the end of the PETP (last participant randomized plus 18 months) were censored at their last known alive date recorded within the PETP. All deaths, regardless of causality or whether they were reported as a reason for study discontinuation, are reported in the All-Cause Mortality section. | Intent-to-Treat Set: all participants who were randomized. As prespecified, data collected and reported as 'Overall (All Randomized Participants)' and per subgroups 'Kappa FLC Subtype' and 'Lambda FLC Subtype'. | Posted | Count of Participants | Participants | Day 1 through end of the participant's PETP (Participants were enrolled on a rolling basis. Therefore, analysis for the study was conducted 18-47 months after the study randomization.) |
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| Secondary | Frequency of CVHs | CVHs were those events that were adjudicated and confirmed as such by the CEAC. Frequency of CEAC-adjudicated CVH was calculated using negative binomial regression analysis with study intervention, study, geographic region, daratumumab usage at Baseline, and offset term equal to log of each participant's follow-up time for cardiovascular hospitalization included in the model. | Intent-to-Treat Set: all participants who were randomized. As prespecified, data collected and reported as 'Overall (All Randomized Participants)' and per subgroups 'Kappa FLC Subtype' and 'Lambda FLC Subtype'. | Posted | Number | 95% Confidence Interval | CV-related hospitalizations/year | Day 1 through end of the participant's PETP (Participants were enrolled on a rolling basis. Therefore, analysis for the study was conducted 18-47 months after the study randomization.) |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in Global Longitudinal Strain (GLS%) | Change in heart function was measured by GLS%, a noninvasive imaging technique that uses echocardiography to assess heart. GLS% expresses longitudinal shortening as a percentage (change in length as a proportion to baseline length) and is reported as a negative value. A more negative value is usually associated with cardiac enhancement. | Intent-to-Treat Set: all participants who were randomized. As prespecified, data collected and reported as 'Overall (All Randomized Participants)' and per subgroups 'Kappa FLC Subtype' and 'Lambda FLC Subtype'. Here, 'Overall Number of Participants Analyzed' and 'Number Analyzed' signifies those participants evaluable for this outcome measure. | Posted | Mean | Standard Deviation | percentage of myocardial shortening | Baseline, Week 50 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in the Short Form-36 (SF-36) Version 2 (v2) Physical Component Score (PCS) | The SF-36v2 is a self-administered questionnaire containing 36 items that measure health on functional status, well-being, and overall evaluation of health in 8 domains, including vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, and mental health, using scaled, ordinal responses (for example, All of the time, Most of the time, A good bit of the time). The SF-36v2 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale, with higher scores indicating an increased quality of life. The 8 multi-item scales are aggregated and summed to give the final PCS. The final score ranges from 0-100, with higher scores indicating an increased quality of life. | Intent-to-Treat Set: all participants who were randomized. As prespecified, data collected and reported for Intent-to-Treat Set. Here, 'Overall Number of Participants Analyzed' signifies those participants evaluable for this outcome measure. | Posted | Mean | Standard Deviation | score on a scale | Baseline, Week 50 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in N-Terminal Pro-B-type Natriuretic Peptide (NT-proBNP) in Blood Samples | For each participant, blood samples were assayed for NT-proBNP, comparing the participant's baseline value over time to assess reduced amyloidosis, as measured by a decrease in NT-proBNP. A decrease indicates cardiac enhancement. Results reported as nanograms/milliliter (ng/mL). | Intent-to-Treat Set: all participants who were randomized. As prespecified, data collected and reported for Intent-to-Treat Set. Here, 'Overall Number of Participants Analyzed' signifies those participants evaluable for this outcome measure. | Posted | Mean | Standard Deviation | ng/mL | Baseline, Week 50 |
|
Day 1 through end of the participant's PETP (Participants were enrolled on a rolling basis. Therefore, safety analysis for the study was conducted 18-47 months after the study randomization.)
Serious and non-serious adverse events based upon the Safety Set: all randomized participants who received at least 1 dose of study intervention. All-cause mortality based upon the Intent-to-treat Set: all participants who were randomized.
All deaths, regardless of causality or whether they were reported as a reason for study discontinuation, are reported in the All-Cause Mortality section. Only deaths indicated as leading to study discontinuation are reported in the Participant Flow section.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | CAEL-101 + Plasma Cell Dyscrasia Treatment | During the PETP, participants were administered CAEL-101 as an IV infusion over approximately 2 hours, in addition to SoC plasma cell dyscrasia treatment. All participants continued their double-blind treatment until LPI+18 months. All participants had the option to enter into the OLEP, where they continued to receive CAEL-101 in addition to any SoC prescribed by a physician. | 46 | 84 | 73 | 84 | 77 | 84 |
| EG001 | Placebo + Plasma Cell Dyscrasia Treatment | During the PETP, participants were administered placebo as an IV infusion over approximately 2 hours, in addition to SoC plasma cell dyscrasia treatment. All participants continued their double-blind treatment until LPI+18 months. All participants had the option to enter into the OLEP, where they continued to receive CAEL-101 in addition to any SoC prescribed by a physician. | 22 | 41 | 33 | 40 | 37 | 40 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Febrile Neutropenia | Blood and lymphatic system disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Splenic Haemorrhage | Blood and lymphatic system disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Cardiac Failure | Cardiac disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Cardiac Arrest | Cardiac disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Cardiac Failure Congestive | Cardiac disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Atrial Fibrillation | Cardiac disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Cardiogenic Shock | Cardiac disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Arrhythmia | Cardiac disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Cardiac Failure Acute | Cardiac disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Cardiorenal Syndrome | Cardiac disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Acute Cardiac Event | Cardiac disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Angina Pectoris | Cardiac disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Atrioventricular Block | Cardiac disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Bradycardia | Cardiac disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Cardiac Amyloidosis | Cardiac disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Myocardial Infarction | Cardiac disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Myocardial Ischaemia | Cardiac disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Pericardial Effusion | Cardiac disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Right Ventricular Failure | Cardiac disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Supraventricular Tachycardia | Cardiac disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Ventricular Tachycardia | Cardiac disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Papilloedema | Eye disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Colitis | Gastrointestinal disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Ascites | Gastrointestinal disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Abdominal Wall Haematoma | Gastrointestinal disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Gastrointestinal Inflammation | Gastrointestinal disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Gastrooesophageal Reflux Disease | Gastrointestinal disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Haematochezia | Gastrointestinal disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Ileus | Gastrointestinal disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Intussusception | Gastrointestinal disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Large Intestinal Obstruction | Gastrointestinal disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Upper Gastrointestinal Haemorrhage | Gastrointestinal disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Multiple Organ Dysfunction Syndrome | General disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Oedema | General disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Oedema Peripheral | General disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Chills | General disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Death | General disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Extravasation | General disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Localised Oedema | General disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Sudden Cardiac Death | General disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Cholecystitis Acute | Hepatobiliary disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Cholelithiasis | Hepatobiliary disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Primary Amyloidosis | Immune system disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Amyloidosis | Immune system disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 28.0 | Systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA 28.0 | Systematic Assessment |
| |
| Covid-19 | Infections and infestations | MedDRA 28.0 | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA 28.0 | Systematic Assessment |
| |
| Covid-19 Pneumonia | Infections and infestations | MedDRA 28.0 | Systematic Assessment |
| |
| Urosepsis | Infections and infestations | MedDRA 28.0 | Systematic Assessment |
| |
| Escherichia Bacteraemia | Infections and infestations | MedDRA 28.0 | Systematic Assessment |
| |
| Escherichia Sepsis | Infections and infestations | MedDRA 28.0 | Systematic Assessment |
| |
| Septic Shock | Infections and infestations | MedDRA 28.0 | Systematic Assessment |
| |
| Urinary Tract Infection | Infections and infestations | MedDRA 28.0 | Systematic Assessment |
| |
| Lower Respiratory Tract Infection | Infections and infestations | MedDRA 28.0 | Systematic Assessment |
| |
| Atypical Pneumonia | Infections and infestations | MedDRA 28.0 | Systematic Assessment |
| |
| Candida Infection | Infections and infestations | MedDRA 28.0 | Systematic Assessment |
| |
| Clostridium Difficile Colitis | Infections and infestations | MedDRA 28.0 | Systematic Assessment |
| |
| Diverticulitis | Infections and infestations | MedDRA 28.0 | Systematic Assessment |
| |
| Endocarditis | Infections and infestations | MedDRA 28.0 | Systematic Assessment |
| |
| Enterococcal Bacteraemia | Infections and infestations | MedDRA 28.0 | Systematic Assessment |
| |
| Enterococcal Sepsis | Infections and infestations | MedDRA 28.0 | Systematic Assessment |
| |
| Enterocolitis Infectious | Infections and infestations | MedDRA 28.0 | Systematic Assessment |
| |
| Epididymitis | Infections and infestations | MedDRA 28.0 | Systematic Assessment |
| |
| Erysipelas | Infections and infestations | MedDRA 28.0 | Systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA 28.0 | Systematic Assessment |
| |
| Gastroenteritis Viral | Infections and infestations | MedDRA 28.0 | Systematic Assessment |
| |
| Herpes Zoster | Infections and infestations | MedDRA 28.0 | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA 28.0 | Systematic Assessment |
| |
| Ludwig Angina | Infections and infestations | MedDRA 28.0 | Systematic Assessment |
| |
| Pneumonia Aspiration | Infections and infestations | MedDRA 28.0 | Systematic Assessment |
| |
| Pneumonia Influenzal | Infections and infestations | MedDRA 28.0 | Systematic Assessment |
| |
| Pneumonia Parainfluenzae Viral | Infections and infestations | MedDRA 28.0 | Systematic Assessment |
| |
| Pseudomonal Bacteraemia | Infections and infestations | MedDRA 28.0 | Systematic Assessment |
| |
| Respiratory Tract Infection | Infections and infestations | MedDRA 28.0 | Systematic Assessment |
| |
| Skin Infection | Infections and infestations | MedDRA 28.0 | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA 28.0 | Systematic Assessment |
| |
| Radiation Pneumonitis | Injury, poisoning and procedural complications | MedDRA 28.0 | Systematic Assessment |
| |
| Shoulder Fracture | Injury, poisoning and procedural complications | MedDRA 28.0 | Systematic Assessment |
| |
| Spinal Fracture | Injury, poisoning and procedural complications | MedDRA 28.0 | Systematic Assessment |
| |
| Thoracic Vertebral Fracture | Injury, poisoning and procedural complications | MedDRA 28.0 | Systematic Assessment |
| |
| Hypervolaemia | Metabolism and nutrition disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Hypovolaemia | Metabolism and nutrition disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Metabolic Acidosis | Metabolism and nutrition disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Metastatic Malignant Melanoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 28.0 | Systematic Assessment |
| |
| Nodular Melanoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 28.0 | Systematic Assessment |
| |
| Small Cell Lung Cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 28.0 | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Cerebrovascular Accident | Nervous system disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Amnestic Disorder | Nervous system disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Cerebral Haematoma | Nervous system disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Cerebral Haemorrhage | Nervous system disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Chronic Inflammatory Demyelinating Polyradiculoneuropathy | Nervous system disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Epilepsy | Nervous system disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Loss Of Consciousness | Nervous system disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Presyncope | Nervous system disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Transient Ischaemic Attack | Nervous system disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Confusional State | Psychiatric disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Delirium | Psychiatric disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Mental Status Changes | Psychiatric disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Acute Kidney Injury | Renal and urinary disorders | MedDRA 28.0 | Systematic Assessment |
| |
| End Stage Renal Disease | Renal and urinary disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Renal Failure | Renal and urinary disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Urinary Retention | Renal and urinary disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Hydrometra | Reproductive system and breast disorders | MedDRA 28.0 | Systematic Assessment | The adverse event affected only female participants. |
|
| Oedema Genital | Reproductive system and breast disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Pleural Effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Pulmonary Embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Respiratory Failure | Respiratory, thoracic and mediastinal disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Acute Respiratory Failure | Respiratory, thoracic and mediastinal disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Diaphragmalgia | Respiratory, thoracic and mediastinal disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Hypercapnia | Respiratory, thoracic and mediastinal disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Immune-Mediated Lung Disease | Respiratory, thoracic and mediastinal disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Pneumothorax Spontaneous | Respiratory, thoracic and mediastinal disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Pulmonary Infarction | Respiratory, thoracic and mediastinal disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Pulmonary Oedema | Respiratory, thoracic and mediastinal disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Rash Pruritic | Skin and subcutaneous tissue disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Embolism | Vascular disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Orthostatic Hypotension | Vascular disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Lymphoedema | Vascular disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Deep Vein Thrombosis | Vascular disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Haematoma | Vascular disorders | MedDRA 28.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Iron Deficiency Anaemia | Blood and lymphatic system disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Cardiac Failure | Cardiac disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Atrial Fibrillation | Cardiac disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Abdominal Pain Upper | Gastrointestinal disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Abdominal Distension | Gastrointestinal disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Abdominal Pain | Gastrointestinal disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Oedema Peripheral | General disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Oedema | General disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Chills | General disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 28.0 | Systematic Assessment |
| |
| Covid-19 | Infections and infestations | MedDRA 28.0 | Systematic Assessment |
| |
| Upper Respiratory Tract Infection | Infections and infestations | MedDRA 28.0 | Systematic Assessment |
| |
| Urinary Tract Infection | Infections and infestations | MedDRA 28.0 | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA 28.0 | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA 28.0 | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA 28.0 | Systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA 28.0 | Systematic Assessment |
| |
| Skin Laceration | Injury, poisoning and procedural complications | MedDRA 28.0 | Systematic Assessment |
| |
| Blood Creatinine Increased | Investigations | MedDRA 28.0 | Systematic Assessment |
| |
| Weight Decreased | Investigations | MedDRA 28.0 | Systematic Assessment |
| |
| Platelet Count Decreased | Investigations | MedDRA 28.0 | Systematic Assessment |
| |
| Blood Alkaline Phosphatase Increased | Investigations | MedDRA 28.0 | Systematic Assessment |
| |
| Aspartate Aminotransferase Increased | Investigations | MedDRA 28.0 | Systematic Assessment |
| |
| Weight Increased | Investigations | MedDRA 28.0 | Systematic Assessment |
| |
| Lymphocyte Count Decreased | Investigations | MedDRA 28.0 | Systematic Assessment |
| |
| Alanine Aminotransferase Increased | Investigations | MedDRA 28.0 | Systematic Assessment |
| |
| White Blood Cell Count Decreased | Investigations | MedDRA 28.0 | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Decreased Appetite | Metabolism and nutrition disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Iron Deficiency | Metabolism and nutrition disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Back Pain | Musculoskeletal and connective tissue disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Pain In Extremity | Musculoskeletal and connective tissue disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Muscular Weakness | Musculoskeletal and connective tissue disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Muscle Spasms | Musculoskeletal and connective tissue disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Peripheral Sensory Neuropathy | Nervous system disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Neuropathy Peripheral | Nervous system disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Presyncope | Nervous system disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Acute Kidney Injury | Renal and urinary disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Chronic Kidney Disease | Renal and urinary disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Pleural Effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Rash Maculo-Papular | Skin and subcutaneous tissue disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Haematoma | Vascular disorders | MedDRA 28.0 | Systematic Assessment |
| |
| Influenza Like Illness | General disorders | MedDRA 28.0 | Systematic Assessment |
|
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Alexion Pharmaceuticals, Inc. | Alexion Pharmaceuticals, Inc. | 1-855-752-2356 | clinicaltrials@alexion.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 15, 2025 | May 8, 2026 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D000075363 | Immunoglobulin Light-chain Amyloidosis |
| D010265 | Paraproteinemias |
| ID | Term |
|---|---|
| D054219 | Neoplasms, Plasma Cell |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D000686 | Amyloidosis |
| D057165 | Proteostasis Deficiencies |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D008232 | Lymphoproliferative Disorders |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D001796 | Blood Protein Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D003520 | Cyclophosphamide |
| D000069286 | Bortezomib |
| D003907 | Dexamethasone |
| D002985 | Clinical Protocols |
| ID | Term |
|---|---|
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D001897 | Boronic Acids |
| D000148 | Acids, Noncarboxylic |
| D000143 | Acids |
| D007287 | Inorganic Chemicals |
| D001896 | Boron Compounds |
| D011719 | Pyrazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011246 | Pregnadienetriols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D013259 | Steroids, Fluorinated |
| D013812 | Therapeutics |
| D016020 | Epidemiologic Study Characteristics |
| D017531 | Health Care Evaluation Mechanisms |
| D011787 | Quality of Health Care |
| D017530 | Health Care Quality, Access, and Evaluation |
Not provided
Not provided
| Kappa FLC Subtype |
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| Lambda FLC Subtype |
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| Kappa FLC Subtype |
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| Lambda FLC Subtype |
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| FLC Subtype Kappa |
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| FLC Subtype Lambda |
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| FLC Subtype Kappa |
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| FLC Subtype Lambda |
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| FLC Subtype Lambda |
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| 0.687 |
| Other |
Treatment Effect Estimation |
| Lambda | Finkelstein-Schoenfeld Test | 0.373 | Other | Treatment Effect Estimation |
During the PETP, participants were administered placebo as an IV infusion over approximately 2 hours, in addition to SoC plasma cell dyscrasia treatment. All participants continued their double-blind treatment until LPI+18 months. All participants had the option to enter into the OLEP, where they continued to receive CAEL-101 in addition to any SoC prescribed by a physician. |
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| Placebo + Plasma Cell Dyscrasia Treatment |
During the PETP, participants were administered placebo as an IV infusion over approximately 2 hours, in addition to SoC plasma cell dyscrasia treatment. All participants continued their double-blind treatment until LPI+18 months. All participants had the option to enter into the OLEP, where they continued to receive CAEL-101 in addition to any SoC prescribed by a physician. |
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| OG001 | Placebo + Plasma Cell Dyscrasia Treatment | During the PETP, participants were administered placebo as an IV infusion over approximately 2 hours, in addition to SoC plasma cell dyscrasia treatment. All participants continued their double-blind treatment until LPI+18 months. All participants had the option to enter into the OLEP, where they continued to receive CAEL-101 in addition to any SoC prescribed by a physician. |
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