Chronic Lymphocytic Leukemia, Non-Hodgkin Lymphoma
Conditions
Keywords
NHL, CLL
Brief summary
The primary objectives of this study are to determine the maximum tolerated dose (MTD) or optimal biologic dose (OBD) and safety profile of CAT-8015 in participants with relapsed or refractory advanced B-cell NHL (diffuse large B-cell lymphoma \[DLBCL\], follicular lymphoma \[FL\], mantle cell lymphoma \[MCL\]) or CLL.
Detailed description
To determine the maximum tolerated dose (MTD) or optimal biologic dose (OBD) of CAT-8015 in participants with relapsed or refractory advanced B-cell NHL (DLBCL, FL, MCL) or CLL.
Interventions
Participants will receive 20 mcg/kg Moxetumomab pasudotox (CAT-8015) as an intravenous (IV) infusion over 30 minutes on Days 1, 3, and 5 of every 28-day cycle.
DRUGCAT-8015 30 mcg/kg
Participants will receive 30 mcg/kg Moxetumomab pasudotox (CAT-8015) as an intravenous (IV) infusion over 30 minutes on Days 1, 3, and 5 of every 28-day cycle.
DRUGCAT-8015 40 mcg/kg
Participants will receive 40 mcg/kg Moxetumomab pasudotox (CAT-8015) as an intravenous (IV) infusion over 30 minutes on Days 1, 3, and 5 of every 28-day cycle.
DRUGCAT-8015 50 mcg/kg
Participants will receive 50 mcg/kg Moxetumomab pasudotox (CAT-8015) as an intravenous (IV) infusion over 30 minutes on Days 1, 3, and 5 of every 28-day cycle.
DRUGCAT-8015 60 mcg/kg
Participants will receive 60 mcg/kg Moxetumomab pasudotox (CAT-8015) as an intravenous (IV) infusion over 30 minutes on Days 1, 3, and 5 of every 28-day cycle.
Sponsors
MedImmune LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
Yes
Inclusion criteria
* Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization * Participants must have histologically confirmed B-cell CLL, including small lymphocytic lymphoma (SLL), DLBCL, MCL, or FL * B-cell NHL: a) Have previous confirmation of B-cell NHL b) Participants with DLBCL or MCL, must have relapsed or refractory disease after at least one prior regimen containing rituximab, either alone or in combination, and be ineligible for any available standard line of therapy known to be life-prolonging or life-saving c) Participants with FL, must have relapsed or refractory disease after at least two prior regimens, one of which included rituximab, either alone or in combination, and be ineligible for any available standard line of therapy known to be life-prolonging or life-saving d) Have measurable disease (at least one lesion greater than or equal to (≥) 20 millimeter (mm) in one dimension or ≥ 15 mm in two dimensions as measured by conventional or high resolution \[spiral\] computed tomography e) Not be a candidate for a hematopoietic stem cell (HSC) or bone marrow transplant * B-cell CLL: a) Have previous confirmation of B-cell CLL with a characteristic immunophenotype by flow cytometry b) Have relapsed or refractory disease after at least 2 prior lines of treatment, at least 1 of which must have contained rituximab and be ineligible for any available standard line of therapy known to be life-prolonging or life-saving c) Not be a candidate for an HSC or BM transplant d) Have symptomatic disease that requires treatment * Karnofsky Performance Status ≥ 70 * Life expectancy of ≥ 12 weeks * Toxicities from previous cancer therapies must have recovered to Grade less than (\<) 2 * Adequate hematological function defined as: a) Hemoglobin ≥ 9 g/dL b) Absolute neutrophil count ≥ 1500/mm\^3 c) Platelet count ≥ 75,000/mm\^3 * Prothrombin time-International Normalized Ratio/Partial thromboplastin time less than or equal to (≤) 1.5 × upper limit of normal (ULN), or for participants on anticoagulation therapy, status within therapeutic range * Women of non-child-bearing potential or using effective contraception * Male participants with partners of child-bearing potential must be surgically sterile or use a contraceptive method
Exclusion criteria
* Any available standard line of therapy known to be life-prolonging or life-saving * Any concurrent chemotherapy, radiotherapy, immunotherapy, biologic, or hormonal therapy for treatment of cancer * For CLL participants only, rapidly progressive disease that in the estimation of the investigator and sponsor would compromise ability to complete study therapy * History of allergy or reaction to any component of the CAT-8015 * Receipt of any chemotherapy or small molecule targeted therapy or any biological- or immunological-based therapies for leukemia or lymphoma within 6 weeks * Prior radiation therapy will not be excluded, providing the volume of bone marrow treated is less than 25 percent * Any history of prior pseudomonas-exotoxin immunotoxin administration including CAT-8015, CAT-3888, or LMB-2 * History of other invasive malignancy within 5 years, with some exceptions * Evidence of significant active infection requiring antimicrobial, antifungal, antiparasitic or antiviral therapy or for which other supportive care is given * Autologous stem cell transplantation within 6 months prior to study entry * Allogenic stem cell transplantation or any other organ transplant * HIV-positive or AIDS, Hepatitis B or hepatitis C infection as defined by seropositive for hepatitis B (HBsAg) or hepatitis C and elevated liver transaminases * Use of immunosuppressive medication other than steroids within 7 days, use of systemic steroids within 7 days before the first dose of CAT-8015 (inhaled and topical corticosteroids are permitted). Participants may take replacement doses of steroids (defined as ≤ 30 mg/day hydrocortisone or the equivalent) if on a stable dose for at least 2 weeks prior to the first dose of CAT-8015 * Documented current central nervous system involvement by leukemia or lymphoma * Pregnancy or lactation, other severe, concurrent diseases * Concurrent enrollment in another clinical study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose (MTD) | Day 1 to end of Cycle 1 (approximately 28 days) | MTD reflects highest dose of drug that did not cause an unacceptable side effect (= Dose Limiting Toxicity \[DLT\]) in more than 30 percent (%) of participants. |
| Number of Participants With Dose Limiting Toxicities (DLTs) | Day 1 to end of Cycle 1 (approximately 28 days) | Any Grade 3 or greater, non-hematological toxicity (including capillary leak syndrome \[CLS\] and thrombotic microangiopathy/ hemolytic uremic syndrome (HUS), Grade 3 or higher treatment-related hematologic toxicities and only ≥ Grade 3 thrombotic microangiopathy /HUS constituted a DLT with few exceptions. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | From Screening (Day -28) to Post Therapy Day 30 | Treatment-emergent adverse event (TEAEs) were defined as events that occur following the first injection of study treatment, or that started prior to the first injection and worsened during treatment. An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An Serious Adverse Event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent adverse events were defined as adverse events/serious adverse events that started or worsened after the study drug treatment. |
| Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | From Screening (Day -28) to Post Therapy Day 30 | Treatment-emergent adverse event (TEAEs) were defined as events that occur following the first injection of study treatment, or that started prior to the first injection and worsened during treatment. An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent adverse events were defined as adverse events/serious adverse events that started or worsened after the study drug treatment. |
| Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | From Screening (Day -28) to Post Therapy Day 30 | Treatment-emergent adverse event (TEAEs) were defined as events that occur following the first injection of study treatment, or that started prior to the first injection and worsened during treatment. An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent adverse events were defined as adverse events/serious adverse events that started or worsened after the study drug treatment. |
| Number of Participants With Electrocardiogram (ECG) Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | From Screening (Day -28) to Post Therapy Day 30 | Treatment-emergent adverse event (TEAEs) were defined as events that occur following the first injection of study treatment, or that started prior to the first injection and worsened during treatment. An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent adverse events were defined as adverse events/serious adverse events that started or worsened after the study drug treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Stable Disease (SD) | Baseline (Day 1) until Final Study Visit Post Therapy (up to 2 year after the last participant begins study drug treatment) | Duration of SD was defined as the time period from start of moxetumomab pasudotox administration to the event of progressive disease (PD)/relapse. Duration of SD was only calculated for the subgroup of participants with best response of CR, PR, or SD, and was calculated using the Kaplan-Meier method. |
| Maximum Plasma Concentration (Cmax) of Moxetumomab Pasudotox | Pre-dose and End of infusion on Day 1, 3 and 5 of each cycle; 1, 3 and 6 hour after the end of infusion on Day 1 of each cycle | Maximum observed drug concentration of Moxetumomab pasudotox in plasma. |
| Area Under Concentration-Time Curve From Dosing Extrapolated to Infinity (AUCinf) of Moxetumomab Pasudotox | Pre-dose and End of infusion on Day 1, 3 and 5 of each cycle; 1, 3 and 6 hour after the end of infusion on Day 1 of each cycle | Area under the concentration versus time curve from zero to infinity (AUC) of Moxetumomab pasudotox in Plasma. |
| Clearance (CL) of Moxetumomab Pasudotox | Pre-dose and End of infusion on Day 1, 3 and 5 of each cycle; 1, 3 and 6 hour after the end of infusion on Day 1 of each cycle | CL of drug is rate at which drug is metabolized or eliminated by normal biological processes and is influenced by fraction of dose absorbed. |
| Percentage of Participants With Complete Response (CR) | Baseline (Day 1) until Final Study Visit Post Therapy (up to 2 year after the last participant begins study drug treatment) | The CR rate was defined as the percentage of participants who had achieved CR based on both the evaluable population for efficacy. |
| Number of Participants With Positive Anti-Drug Antibody | Baseline (Day 1) up to End of the Treatment (Last dose of Last cycle) (approximately 3 years) | The moxetumomab pasudotox specific bridging assay using the Meso Scale Discovery platform was employed to detect anti-drug antibodies (ADA). |
| Number of Participants With CD22 Expression Levels | Baseline (Day 1) up to End of the Treatment (Last dose of Last cycle) (approximately 3 years) | CD22 Expression was analyzed using Prism® analysis. Flow cytometry was performed to quantitate the CD22 expression for the purpose of evaluating the relationship of CD22 expression with response to treatment. |
| Number of Capillary Leak Syndrome (CLS) Participants With Weight Changes, Albumin, Hypotension, Edema, Hypoxia, and Pulmonary Adverse Events (AEs) | From Screening (Day -28) to Post Therapy Day 30 | The correlation of CLS and weight changes, albumin, hypotension, edema, hypoxia, and pulmonary AEs were examined. |
| Percentage of Participants With Stable Disease (SD) | Baseline (Day 1) until Final Study Visit Post Therapy (up to 2 year after the last participant begins study drug treatment) | — |
| Elimination Half Life (t1/2) of Moxetumomab Pasudotox | Pre-dose and End of infusion on Day 1, 3 and 5 of each cycle; 1, 3 and 6 hour after the end of infusion on Day 1 of each cycle | Plasma decay half life is the time measured for the plasma concentration to decrease by one half. |
| Duration of Complete Response | Baseline (Day 1) until Final Study Visit Post Therapy (up to 2 year after the last participant begins study drug treatment) | Duration of CR was measured from the first documentation of a CR to the time of relapse for the subgroup of participants with CR. Duration of CR was calculated using the Kaplan Meier method. The Evaluable Population for efficacy was used to evaluate the endpoints for the efficacy profile. |
| Percentage of Participants With Partial Response (PR) | Baseline (Day 1) until Final Study Visit Post Therapy (up to 2 year after the last participant begins study drug treatment) | — |
| Percentage of Participants With Objective Response (OR) | Baseline (Day 1) until Final Study Visit Post Therapy (up to 2 year after the last participant begins study drug treatment) | OR was defined as the percentage of participants with CR or partial response (PR). |
| Time to Response (TTR) | Baseline (Day 1) until Final Study Visit Post Therapy (up to 2 year after the last participant begins study drug treatment) | TTR was measured from the start of moxetumomab pasudotox administration to the first documentation of response (CR or PR) and was only assessed in participants who had achieved objective response (OR). |
| Duration of Objective Response (DOR) | Baseline (Day 1) until Final Study Visit Post Therapy (up to 2 year after the last participant begins study drug treatment) | DOR was measured from the first documentation of OR to the event of relapse. DOR was calculated using the Kaplan-Meier method. |
Countries
Poland, United States
Participant flow
Recruitment details
Study was started on 15 Feb 2010 and was terminated on 12 Sep 2012. The Product Development Team authorized early termination of this study due to prioritization of resources and the need to prioritize allocation of investigational product across the studies in the moxetumomab pasudotox clinical development program.
Pre-assignment details
A total of 30 participants were screened and enrolled, of them 7 were failed screening. Twenty three participants were enrolled and assigned to treatment at 6 sites in the United States.
Participants by arm
| Arm | Count |
|---|---|
| CAT-8015 20 Microgram Per Kilogram (mcg/kg) Participants received 20 mcg/kg Moxetumomab pasudotox (CAT-8015) as an intravenous (IV) infusion over 30 minutes on Days 1, 3, and 5 of every 28-day cycle. Dose escalation was to be continued to the Maximum tolerated dose (MTD) or Optimal biologic dose (OBD). Subsequent dose levels with a 10 mcg/kg increase from the previous dose level were possible if an MTD or OBD was not reached by 60 mcg/kg. | 7 |
| CAT-8015 30 Microgram Per Kilogram (mcg/kg) Participants received 30 mcg/kg Moxetumomab pasudotox (CAT-8015) as an intravenous (IV) infusion over 30 minutes on Days 1, 3, and 5 of every 28-day cycle. Dose escalation was to be continued to the Maximum tolerated dose (MTD) or Optimal biologic dose (OBD). Subsequent dose levels with a 10 mcg/kg increase from the previous dose level were possible if an MTD or OBD was not reached by 60 mcg/kg. | 6 |
| CAT-8015 40 Microgram Per Kilogram (mcg/kg) Participants received 40 mcg/kg Moxetumomab pasudotox (CAT-8015) as an intravenous (IV) infusion over 30 minutes on Days 1, 3, and 5 of every 28-day cycle. Dose escalation was to be continued to the Maximum tolerated dose (MTD) or Optimal biologic dose (OBD). Subsequent dose levels with a 10 mcg/kg increase from the previous dose level were possible if an MTD or OBD was not reached by 60 mcg/kg. | 6 |
| CAT-8015 50 Microgram Per Kilogram (mcg/kg) Participants received 50 mcg/kg Moxetumomab pasudotox (CAT-8015) as an intravenous (IV) infusion over 30 minutes on Days 1, 3, and 5 of every 28-day cycle. Dose escalation was to be continued to the Maximum tolerated dose (MTD) or Optimal biologic dose (OBD). Subsequent dose levels with a 10 mcg/kg increase from the previous dose level were possible if an MTD or OBD was not reached by 60 mcg/kg. | 3 |
| CAT-8015 60 Microgram Per Kilogram (mcg/kg) Participants received 60 mcg/kg Moxetumomab pasudotox (CAT-8015) as an intravenous (IV) infusion over 30 minutes on Days 1, 3, and 5 of every 28-day cycle. Dose escalation was to be continued to the Maximum tolerated dose (MTD) or Optimal biologic dose (OBD). Subsequent dose levels with a 10 mcg/kg increase from the previous dose level were possible if an MTD or OBD was not reached by 60 mcg/kg. | 1 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 3 | 1 | 0 | 1 |
| Overall Study | Death | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Progressive disease | 6 | 2 | 3 | 2 | 0 |
| Overall Study | undefined | 1 | 0 | 1 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | CAT-8015 20 Microgram Per Kilogram (mcg/kg) | CAT-8015 30 Microgram Per Kilogram (mcg/kg) | CAT-8015 40 Microgram Per Kilogram (mcg/kg) | CAT-8015 50 Microgram Per Kilogram (mcg/kg) | CAT-8015 60 Microgram Per Kilogram (mcg/kg) | Total |
|---|---|---|---|---|---|---|
| Age, Continuous Age | 63.4 years STANDARD_DEVIATION 8.7 | 53.7 years STANDARD_DEVIATION 16.9 | 63.5 years STANDARD_DEVIATION 10 | 52.3 years STANDARD_DEVIATION 14.6 | 66.0 years | 59.6 years STANDARD_DEVIATION 12.4 |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 4 Participants |
| Sex: Female, Male Male | 5 Participants | 5 Participants | 6 Participants | 3 Participants | 0 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 7 / 7 | 6 / 6 | 6 / 6 | 3 / 3 | 1 / 1 |
| serious Total, serious adverse events | 0 / 7 | 3 / 6 | 2 / 6 | 0 / 3 | 1 / 1 |
Outcome results
Primary
Maximum Tolerated Dose (MTD)
MTD reflects highest dose of drug that did not cause an unacceptable side effect (= Dose Limiting Toxicity \[DLT\]) in more than 30 percent (%) of participants.
Time frame: Day 1 to end of Cycle 1 (approximately 28 days)
Population: Evaluable Population for DLT included all participants enrolled in the dose-escalation phase who received at least one full cycle of moxetumomab pasudotox and completed safety follow-up through the DLT evaluation period or experienced any DLT.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CAT-8015 20 Microgram Per Kilogram (mcg/kg) | Maximum Tolerated Dose (MTD) | NA mcg/Kg |
| CAT-8015 30 Microgram Per Kilogram (mcg/kg) | Maximum Tolerated Dose (MTD) | NA mcg/Kg |
| CAT-8015 40 Microgram Per Kilogram (mcg/kg) | Maximum Tolerated Dose (MTD) | NA mcg/Kg |
| CAT-8015 50 Microgram Per Kilogram (mcg/kg) | Maximum Tolerated Dose (MTD) | NA mcg/Kg |
| CAT-8015 60 Microgram Per Kilogram (mcg/kg) | Maximum Tolerated Dose (MTD) | NA mcg/Kg |
Primary
Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs)
Treatment-emergent adverse event (TEAEs) were defined as events that occur following the first injection of study treatment, or that started prior to the first injection and worsened during treatment. An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent adverse events were defined as adverse events/serious adverse events that started or worsened after the study drug treatment.
Time frame: From Screening (Day -28) to Post Therapy Day 30
Population: Safety Population included all participants who received moxetumomab pasudotox. The safety population was used to evaluate baseline characteristics as well as all endpoints for safety.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CAT-8015 20 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypocalcaemia | 0 Participants |
| CAT-8015 20 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hyperglycaemia | 0 Participants |
| CAT-8015 20 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Aspartate aminotransferase increased | 1 Participants |
| CAT-8015 20 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypercalcaemia | 0 Participants |
| CAT-8015 20 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypokalaemia | 0 Participants |
| CAT-8015 20 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hyperlipidaemia | 0 Participants |
| CAT-8015 20 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood alkaline phosphatase increased | 0 Participants |
| CAT-8015 20 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Platelet count decreased | 0 Participants |
| CAT-8015 20 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hematuria | 0 Participants |
| CAT-8015 20 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hyperchlorhydria | 0 Participants |
| CAT-8015 20 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Thrombocytopenia | 0 Participants |
| CAT-8015 20 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Neutrophil count decreased | 1 Participants |
| CAT-8015 20 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Haptoglobin decreased | 0 Participants |
| CAT-8015 20 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Leukocytosis | 0 Participants |
| CAT-8015 20 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood triglycerides increased | 0 Participants |
| CAT-8015 20 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypoalbuminaemia | 2 Participants |
| CAT-8015 20 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood bilirubin increased | 1 Participants |
| CAT-8015 20 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypertriglyceridaemia | 0 Participants |
| CAT-8015 20 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood bicarbonate increased | 0 Participants |
| CAT-8015 20 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hyponatraemia | 0 Participants |
| CAT-8015 20 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypermagnesaemia | 0 Participants |
| CAT-8015 20 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood albumin decreased | 1 Participants |
| CAT-8015 20 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Alanine aminotransferase increased | 1 Participants |
| CAT-8015 20 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Neutropenia | 1 Participants |
| CAT-8015 20 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypophosphataemia | 0 Participants |
| CAT-8015 20 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood creatinine increased | 1 Participants |
| CAT-8015 20 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hyperuricaemia | 1 Participants |
| CAT-8015 20 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypernatraemia | 2 Participants |
| CAT-8015 20 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Anaemia | 0 Participants |
| CAT-8015 20 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hyperkalaemia | 0 Participants |
| CAT-8015 30 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Neutropenia | 1 Participants |
| CAT-8015 30 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypocalcaemia | 1 Participants |
| CAT-8015 30 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hematuria | 1 Participants |
| CAT-8015 30 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hyperglycaemia | 1 Participants |
| CAT-8015 30 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypoalbuminaemia | 1 Participants |
| CAT-8015 30 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Anaemia | 3 Participants |
| CAT-8015 30 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Aspartate aminotransferase increased | 1 Participants |
| CAT-8015 30 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hyperlipidaemia | 0 Participants |
| CAT-8015 30 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypercalcaemia | 1 Participants |
| CAT-8015 30 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood bilirubin increased | 0 Participants |
| CAT-8015 30 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Alanine aminotransferase increased | 1 Participants |
| CAT-8015 30 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypokalaemia | 0 Participants |
| CAT-8015 30 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hyperuricaemia | 0 Participants |
| CAT-8015 30 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood alkaline phosphatase increased | 0 Participants |
| CAT-8015 30 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypertriglyceridaemia | 3 Participants |
| CAT-8015 30 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypermagnesaemia | 0 Participants |
| CAT-8015 30 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Platelet count decreased | 0 Participants |
| CAT-8015 30 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood bicarbonate increased | 0 Participants |
| CAT-8015 30 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hyperchlorhydria | 0 Participants |
| CAT-8015 30 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypophosphataemia | 0 Participants |
| CAT-8015 30 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypernatraemia | 0 Participants |
| CAT-8015 30 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Thrombocytopenia | 2 Participants |
| CAT-8015 30 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hyponatraemia | 1 Participants |
| CAT-8015 30 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Haptoglobin decreased | 0 Participants |
| CAT-8015 30 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hyperkalaemia | 1 Participants |
| CAT-8015 30 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood albumin decreased | 0 Participants |
| CAT-8015 30 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Leukocytosis | 1 Participants |
| CAT-8015 30 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Neutrophil count decreased | 0 Participants |
| CAT-8015 30 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood triglycerides increased | 1 Participants |
| CAT-8015 30 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood creatinine increased | 2 Participants |
| CAT-8015 40 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypernatraemia | 1 Participants |
| CAT-8015 40 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Anaemia | 3 Participants |
| CAT-8015 40 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Neutrophil count decreased | 0 Participants |
| CAT-8015 40 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Neutropenia | 0 Participants |
| CAT-8015 40 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Platelet count decreased | 1 Participants |
| CAT-8015 40 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Thrombocytopenia | 0 Participants |
| CAT-8015 40 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Leukocytosis | 0 Participants |
| CAT-8015 40 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypoalbuminaemia | 2 Participants |
| CAT-8015 40 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypertriglyceridaemia | 0 Participants |
| CAT-8015 40 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hyponatraemia | 3 Participants |
| CAT-8015 40 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Alanine aminotransferase increased | 0 Participants |
| CAT-8015 40 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood creatinine increased | 0 Participants |
| CAT-8015 40 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypocalcaemia | 2 Participants |
| CAT-8015 40 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Aspartate aminotransferase increased | 0 Participants |
| CAT-8015 40 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypokalaemia | 1 Participants |
| CAT-8015 40 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood alkaline phosphatase increased | 0 Participants |
| CAT-8015 40 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypercalcaemia | 0 Participants |
| CAT-8015 40 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hyperglycaemia | 1 Participants |
| CAT-8015 40 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hyperkalaemia | 1 Participants |
| CAT-8015 40 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hyperuricaemia | 0 Participants |
| CAT-8015 40 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypophosphataemia | 1 Participants |
| CAT-8015 40 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood albumin decreased | 0 Participants |
| CAT-8015 40 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood bicarbonate increased | 0 Participants |
| CAT-8015 40 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood bilirubin increased | 0 Participants |
| CAT-8015 40 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood triglycerides increased | 0 Participants |
| CAT-8015 40 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Haptoglobin decreased | 0 Participants |
| CAT-8015 40 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hyperchlorhydria | 1 Participants |
| CAT-8015 40 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hyperlipidaemia | 1 Participants |
| CAT-8015 40 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypermagnesaemia | 0 Participants |
| CAT-8015 40 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hematuria | 1 Participants |
| CAT-8015 50 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hyperkalaemia | 0 Participants |
| CAT-8015 50 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Leukocytosis | 0 Participants |
| CAT-8015 50 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hyperuricaemia | 0 Participants |
| CAT-8015 50 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood triglycerides increased | 0 Participants |
| CAT-8015 50 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hyponatraemia | 0 Participants |
| CAT-8015 50 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Neutrophil count decreased | 1 Participants |
| CAT-8015 50 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Thrombocytopenia | 0 Participants |
| CAT-8015 50 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood albumin decreased | 0 Participants |
| CAT-8015 50 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Haptoglobin decreased | 0 Participants |
| CAT-8015 50 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypernatraemia | 0 Participants |
| CAT-8015 50 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hyperlipidaemia | 0 Participants |
| CAT-8015 50 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Platelet count decreased | 0 Participants |
| CAT-8015 50 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Anaemia | 0 Participants |
| CAT-8015 50 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hyperchlorhydria | 0 Participants |
| CAT-8015 50 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypertriglyceridaemia | 1 Participants |
| CAT-8015 50 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hematuria | 0 Participants |
| CAT-8015 50 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypokalaemia | 1 Participants |
| CAT-8015 50 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood bicarbonate increased | 0 Participants |
| CAT-8015 50 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood alkaline phosphatase increased | 1 Participants |
| CAT-8015 50 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Alanine aminotransferase increased | 1 Participants |
| CAT-8015 50 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood creatinine increased | 0 Participants |
| CAT-8015 50 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Aspartate aminotransferase increased | 1 Participants |
| CAT-8015 50 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Neutropenia | 0 Participants |
| CAT-8015 50 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypercalcaemia | 0 Participants |
| CAT-8015 50 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypoalbuminaemia | 0 Participants |
| CAT-8015 50 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypermagnesaemia | 0 Participants |
| CAT-8015 50 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypocalcaemia | 0 Participants |
| CAT-8015 50 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood bilirubin increased | 0 Participants |
| CAT-8015 50 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hyperglycaemia | 0 Participants |
| CAT-8015 50 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypophosphataemia | 1 Participants |
| CAT-8015 60 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hyperglycaemia | 0 Participants |
| CAT-8015 60 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hyperkalaemia | 0 Participants |
| CAT-8015 60 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood creatinine increased | 1 Participants |
| CAT-8015 60 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hyperlipidaemia | 0 Participants |
| CAT-8015 60 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hyperuricaemia | 1 Participants |
| CAT-8015 60 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Alanine aminotransferase increased | 1 Participants |
| CAT-8015 60 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Neutrophil count decreased | 1 Participants |
| CAT-8015 60 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypophosphataemia | 0 Participants |
| CAT-8015 60 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hyponatraemia | 1 Participants |
| CAT-8015 60 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood albumin decreased | 0 Participants |
| CAT-8015 60 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypertriglyceridaemia | 1 Participants |
| CAT-8015 60 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood bicarbonate increased | 1 Participants |
| CAT-8015 60 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypoalbuminaemia | 1 Participants |
| CAT-8015 60 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood bilirubin increased | 0 Participants |
| CAT-8015 60 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Leukocytosis | 0 Participants |
| CAT-8015 60 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypermagnesaemia | 1 Participants |
| CAT-8015 60 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood triglycerides increased | 0 Participants |
| CAT-8015 60 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Thrombocytopenia | 0 Participants |
| CAT-8015 60 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Anaemia | 1 Participants |
| CAT-8015 60 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Haptoglobin decreased | 1 Participants |
| CAT-8015 60 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Platelet count decreased | 1 Participants |
| CAT-8015 60 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hyperchlorhydria | 0 Participants |
| CAT-8015 60 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypokalaemia | 1 Participants |
| CAT-8015 60 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Neutropenia | 0 Participants |
| CAT-8015 60 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood alkaline phosphatase increased | 1 Participants |
| CAT-8015 60 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Aspartate aminotransferase increased | 0 Participants |
| CAT-8015 60 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypercalcaemia | 1 Participants |
| CAT-8015 60 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypocalcaemia | 1 Participants |
| CAT-8015 60 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hematuria | 1 Participants |
| CAT-8015 60 Microgram Per Kilogram (mcg/kg) | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypernatraemia | 1 Participants |
Primary
Number of Participants With Dose Limiting Toxicities (DLTs)
Any Grade 3 or greater, non-hematological toxicity (including capillary leak syndrome \[CLS\] and thrombotic microangiopathy/ hemolytic uremic syndrome (HUS), Grade 3 or higher treatment-related hematologic toxicities and only ≥ Grade 3 thrombotic microangiopathy /HUS constituted a DLT with few exceptions.
Time frame: Day 1 to end of Cycle 1 (approximately 28 days)
Population: Evaluable Population for DLT included all participants enrolled in the dose-escalation phase who received at least one full cycle of moxetumomab pasudotox and completed safety follow-up through the DLT evaluation period or experienced any DLT.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CAT-8015 20 Microgram Per Kilogram (mcg/kg) | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| CAT-8015 30 Microgram Per Kilogram (mcg/kg) | Number of Participants With Dose Limiting Toxicities (DLTs) | 2 Participants |
| CAT-8015 40 Microgram Per Kilogram (mcg/kg) | Number of Participants With Dose Limiting Toxicities (DLTs) | 1 Participants |
| CAT-8015 50 Microgram Per Kilogram (mcg/kg) | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| CAT-8015 60 Microgram Per Kilogram (mcg/kg) | Number of Participants With Dose Limiting Toxicities (DLTs) | 1 Participants |
Primary
Number of Participants With Electrocardiogram (ECG) Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs)
Treatment-emergent adverse event (TEAEs) were defined as events that occur following the first injection of study treatment, or that started prior to the first injection and worsened during treatment. An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent adverse events were defined as adverse events/serious adverse events that started or worsened after the study drug treatment.
Time frame: From Screening (Day -28) to Post Therapy Day 30
Population: Safety Population included all participants who received moxetumomab pasudotox. The safety population was used to evaluate baseline characteristics as well as all endpoints for safety.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CAT-8015 20 Microgram Per Kilogram (mcg/kg) | Number of Participants With Electrocardiogram (ECG) Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Sinus Tachycardia | 0 Participants |
| CAT-8015 20 Microgram Per Kilogram (mcg/kg) | Number of Participants With Electrocardiogram (ECG) Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | ECG QT Prolonged | 2 Participants |
| CAT-8015 30 Microgram Per Kilogram (mcg/kg) | Number of Participants With Electrocardiogram (ECG) Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Sinus Tachycardia | 1 Participants |
| CAT-8015 30 Microgram Per Kilogram (mcg/kg) | Number of Participants With Electrocardiogram (ECG) Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | ECG QT Prolonged | 0 Participants |
| CAT-8015 40 Microgram Per Kilogram (mcg/kg) | Number of Participants With Electrocardiogram (ECG) Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Sinus Tachycardia | 0 Participants |
| CAT-8015 40 Microgram Per Kilogram (mcg/kg) | Number of Participants With Electrocardiogram (ECG) Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | ECG QT Prolonged | 0 Participants |
| CAT-8015 50 Microgram Per Kilogram (mcg/kg) | Number of Participants With Electrocardiogram (ECG) Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | ECG QT Prolonged | 0 Participants |
| CAT-8015 50 Microgram Per Kilogram (mcg/kg) | Number of Participants With Electrocardiogram (ECG) Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Sinus Tachycardia | 0 Participants |
| CAT-8015 60 Microgram Per Kilogram (mcg/kg) | Number of Participants With Electrocardiogram (ECG) Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Sinus Tachycardia | 0 Participants |
| CAT-8015 60 Microgram Per Kilogram (mcg/kg) | Number of Participants With Electrocardiogram (ECG) Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | ECG QT Prolonged | 0 Participants |
Primary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
Treatment-emergent adverse event (TEAEs) were defined as events that occur following the first injection of study treatment, or that started prior to the first injection and worsened during treatment. An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An Serious Adverse Event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent adverse events were defined as adverse events/serious adverse events that started or worsened after the study drug treatment.
Time frame: From Screening (Day -28) to Post Therapy Day 30
Population: Safety Population included all participants who received moxetumomab pasudotox. The safety population was used to evaluate baseline characteristics as well as all endpoints for safety.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CAT-8015 20 Microgram Per Kilogram (mcg/kg) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAEs | 7 Participants |
| CAT-8015 20 Microgram Per Kilogram (mcg/kg) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TESAEs | 0 Participants |
| CAT-8015 30 Microgram Per Kilogram (mcg/kg) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAEs | 6 Participants |
| CAT-8015 30 Microgram Per Kilogram (mcg/kg) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TESAEs | 3 Participants |
| CAT-8015 40 Microgram Per Kilogram (mcg/kg) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAEs | 6 Participants |
| CAT-8015 40 Microgram Per Kilogram (mcg/kg) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TESAEs | 2 Participants |
| CAT-8015 50 Microgram Per Kilogram (mcg/kg) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TESAEs | 0 Participants |
| CAT-8015 50 Microgram Per Kilogram (mcg/kg) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAEs | 3 Participants |
| CAT-8015 60 Microgram Per Kilogram (mcg/kg) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAEs | 1 Participants |
| CAT-8015 60 Microgram Per Kilogram (mcg/kg) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TESAEs | 1 Participants |
Primary
Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs)
Treatment-emergent adverse event (TEAEs) were defined as events that occur following the first injection of study treatment, or that started prior to the first injection and worsened during treatment. An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent adverse events were defined as adverse events/serious adverse events that started or worsened after the study drug treatment.
Time frame: From Screening (Day -28) to Post Therapy Day 30
Population: Safety Population included all participants who received moxetumomab pasudotox. The safety population was used to evaluate baseline characteristics as well as all endpoints for safety.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CAT-8015 20 Microgram Per Kilogram (mcg/kg) | Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Weight Increased | 1 Participants |
| CAT-8015 20 Microgram Per Kilogram (mcg/kg) | Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Pyrexia | 0 Participants |
| CAT-8015 20 Microgram Per Kilogram (mcg/kg) | Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypertension | 0 Participants |
| CAT-8015 20 Microgram Per Kilogram (mcg/kg) | Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypotension | 1 Participants |
| CAT-8015 30 Microgram Per Kilogram (mcg/kg) | Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypotension | 1 Participants |
| CAT-8015 30 Microgram Per Kilogram (mcg/kg) | Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Weight Increased | 0 Participants |
| CAT-8015 30 Microgram Per Kilogram (mcg/kg) | Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Pyrexia | 1 Participants |
| CAT-8015 30 Microgram Per Kilogram (mcg/kg) | Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypertension | 2 Participants |
| CAT-8015 40 Microgram Per Kilogram (mcg/kg) | Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Weight Increased | 0 Participants |
| CAT-8015 40 Microgram Per Kilogram (mcg/kg) | Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Pyrexia | 1 Participants |
| CAT-8015 40 Microgram Per Kilogram (mcg/kg) | Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypertension | 1 Participants |
| CAT-8015 40 Microgram Per Kilogram (mcg/kg) | Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypotension | 1 Participants |
| CAT-8015 50 Microgram Per Kilogram (mcg/kg) | Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Weight Increased | 0 Participants |
| CAT-8015 50 Microgram Per Kilogram (mcg/kg) | Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypotension | 0 Participants |
| CAT-8015 50 Microgram Per Kilogram (mcg/kg) | Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Pyrexia | 0 Participants |
| CAT-8015 50 Microgram Per Kilogram (mcg/kg) | Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypertension | 0 Participants |
| CAT-8015 60 Microgram Per Kilogram (mcg/kg) | Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypertension | 0 Participants |
| CAT-8015 60 Microgram Per Kilogram (mcg/kg) | Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Weight Increased | 0 Participants |
| CAT-8015 60 Microgram Per Kilogram (mcg/kg) | Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Pyrexia | 0 Participants |
| CAT-8015 60 Microgram Per Kilogram (mcg/kg) | Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypotension | 1 Participants |
Secondary
Area Under Concentration-Time Curve From Dosing Extrapolated to Infinity (AUCinf) of Moxetumomab Pasudotox
Area under the concentration versus time curve from zero to infinity (AUC) of Moxetumomab pasudotox in Plasma.
Time frame: Pre-dose and End of infusion on Day 1, 3 and 5 of each cycle; 1, 3 and 6 hour after the end of infusion on Day 1 of each cycle
Population: Evaluable Population for efficacy included all participants who received any moxetumomab pasudotox treatment and completed at least one post-baseline disease assessment. The Evaluable Population for efficacy was used to evaluate the endpoints for the efficacy profile.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CAT-8015 20 Microgram Per Kilogram (mcg/kg) | Area Under Concentration-Time Curve From Dosing Extrapolated to Infinity (AUCinf) of Moxetumomab Pasudotox | 1120 hour*nanogram per milliliter (hr*ng/mL) | Standard Deviation 928 |
| CAT-8015 30 Microgram Per Kilogram (mcg/kg) | Area Under Concentration-Time Curve From Dosing Extrapolated to Infinity (AUCinf) of Moxetumomab Pasudotox | 1640 hour*nanogram per milliliter (hr*ng/mL) | Standard Deviation 682 |
| CAT-8015 40 Microgram Per Kilogram (mcg/kg) | Area Under Concentration-Time Curve From Dosing Extrapolated to Infinity (AUCinf) of Moxetumomab Pasudotox | 2050 hour*nanogram per milliliter (hr*ng/mL) | Standard Deviation 1150 |
| CAT-8015 50 Microgram Per Kilogram (mcg/kg) | Area Under Concentration-Time Curve From Dosing Extrapolated to Infinity (AUCinf) of Moxetumomab Pasudotox | 2320 hour*nanogram per milliliter (hr*ng/mL) | Standard Deviation 1010 |
| CAT-8015 60 Microgram Per Kilogram (mcg/kg) | Area Under Concentration-Time Curve From Dosing Extrapolated to Infinity (AUCinf) of Moxetumomab Pasudotox | 1810 hour*nanogram per milliliter (hr*ng/mL) | — |
Secondary
Clearance (CL) of Moxetumomab Pasudotox
CL of drug is rate at which drug is metabolized or eliminated by normal biological processes and is influenced by fraction of dose absorbed.
Time frame: Pre-dose and End of infusion on Day 1, 3 and 5 of each cycle; 1, 3 and 6 hour after the end of infusion on Day 1 of each cycle
Population: Evaluable Population for efficacy included all participants who received any moxetumomab pasudotox treatment and completed at least one post-baseline disease assessment. The Evaluable Population for efficacy was used to evaluate the endpoints for the efficacy profile.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CAT-8015 20 Microgram Per Kilogram (mcg/kg) | Clearance (CL) of Moxetumomab Pasudotox | 31.6 milliliter per hour per kilogram | Standard Deviation 25.5 |
| CAT-8015 30 Microgram Per Kilogram (mcg/kg) | Clearance (CL) of Moxetumomab Pasudotox | 22.2 milliliter per hour per kilogram | Standard Deviation 12.5 |
| CAT-8015 40 Microgram Per Kilogram (mcg/kg) | Clearance (CL) of Moxetumomab Pasudotox | 26.9 milliliter per hour per kilogram | Standard Deviation 18.6 |
| CAT-8015 50 Microgram Per Kilogram (mcg/kg) | Clearance (CL) of Moxetumomab Pasudotox | 25.2 milliliter per hour per kilogram | Standard Deviation 12.9 |
| CAT-8015 60 Microgram Per Kilogram (mcg/kg) | Clearance (CL) of Moxetumomab Pasudotox | 33.1 milliliter per hour per kilogram | — |
Secondary
Duration of Complete Response
Duration of CR was measured from the first documentation of a CR to the time of relapse for the subgroup of participants with CR. Duration of CR was calculated using the Kaplan Meier method. The Evaluable Population for efficacy was used to evaluate the endpoints for the efficacy profile.
Time frame: Baseline (Day 1) until Final Study Visit Post Therapy (up to 2 year after the last participant begins study drug treatment)
Population: Evaluable Population for efficacy included all participants who received any moxetumomab pasudotox treatment and completed at least one post-baseline disease assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CAT-8015 20 Microgram Per Kilogram (mcg/kg) | Duration of Complete Response | NA Months |
| CAT-8015 30 Microgram Per Kilogram (mcg/kg) | Duration of Complete Response | NA Months |
| CAT-8015 40 Microgram Per Kilogram (mcg/kg) | Duration of Complete Response | NA Months |
| CAT-8015 50 Microgram Per Kilogram (mcg/kg) | Duration of Complete Response | NA Months |
Secondary
Duration of Objective Response (DOR)
DOR was measured from the first documentation of OR to the event of relapse. DOR was calculated using the Kaplan-Meier method.
Time frame: Baseline (Day 1) until Final Study Visit Post Therapy (up to 2 year after the last participant begins study drug treatment)
Population: Evaluable Population for efficacy included all participants who received any moxetumomab pasudotox treatment and completed at least one post-baseline disease assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CAT-8015 20 Microgram Per Kilogram (mcg/kg) | Duration of Objective Response (DOR) | 7.66 Months |
| CAT-8015 30 Microgram Per Kilogram (mcg/kg) | Duration of Objective Response (DOR) | NA Months |
| CAT-8015 40 Microgram Per Kilogram (mcg/kg) | Duration of Objective Response (DOR) | NA Months |
| CAT-8015 50 Microgram Per Kilogram (mcg/kg) | Duration of Objective Response (DOR) | NA Months |
Secondary
Duration of Stable Disease (SD)
Duration of SD was defined as the time period from start of moxetumomab pasudotox administration to the event of progressive disease (PD)/relapse. Duration of SD was only calculated for the subgroup of participants with best response of CR, PR, or SD, and was calculated using the Kaplan-Meier method.
Time frame: Baseline (Day 1) until Final Study Visit Post Therapy (up to 2 year after the last participant begins study drug treatment)
Population: Evaluable Population for efficacy included all participants who received any moxetumomab pasudotox treatment and completed at least one post-baseline disease assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CAT-8015 20 Microgram Per Kilogram (mcg/kg) | Duration of Stable Disease (SD) | 1.87 Months |
| CAT-8015 30 Microgram Per Kilogram (mcg/kg) | Duration of Stable Disease (SD) | NA Months |
| CAT-8015 40 Microgram Per Kilogram (mcg/kg) | Duration of Stable Disease (SD) | 0.95 Months |
| CAT-8015 50 Microgram Per Kilogram (mcg/kg) | Duration of Stable Disease (SD) | 4.67 Months |
Secondary
Elimination Half Life (t1/2) of Moxetumomab Pasudotox
Plasma decay half life is the time measured for the plasma concentration to decrease by one half.
Time frame: Pre-dose and End of infusion on Day 1, 3 and 5 of each cycle; 1, 3 and 6 hour after the end of infusion on Day 1 of each cycle
Population: Evaluable Population for efficacy included all participants who received any moxetumomab pasudotox treatment and completed at least one post-baseline disease assessment. The Evaluable Population for efficacy was used to evaluate the endpoints for the efficacy profile.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CAT-8015 20 Microgram Per Kilogram (mcg/kg) | Elimination Half Life (t1/2) of Moxetumomab Pasudotox | 1.55 hour | Standard Deviation 1.1 |
| CAT-8015 30 Microgram Per Kilogram (mcg/kg) | Elimination Half Life (t1/2) of Moxetumomab Pasudotox | 1.87 hour | Standard Deviation 0.985 |
| CAT-8015 40 Microgram Per Kilogram (mcg/kg) | Elimination Half Life (t1/2) of Moxetumomab Pasudotox | 1.68 hour | Standard Deviation 0.726 |
| CAT-8015 50 Microgram Per Kilogram (mcg/kg) | Elimination Half Life (t1/2) of Moxetumomab Pasudotox | 1.87 hour | Standard Deviation 0.586 |
| CAT-8015 60 Microgram Per Kilogram (mcg/kg) | Elimination Half Life (t1/2) of Moxetumomab Pasudotox | 0.901 hour | — |
Secondary
Maximum Plasma Concentration (Cmax) of Moxetumomab Pasudotox
Maximum observed drug concentration of Moxetumomab pasudotox in plasma.
Time frame: Pre-dose and End of infusion on Day 1, 3 and 5 of each cycle; 1, 3 and 6 hour after the end of infusion on Day 1 of each cycle
Population: Evaluable Population for efficacy included all participants who received any moxetumomab pasudotox treatment and completed at least one post-baseline disease assessment. The Evaluable Population for efficacy was used to evaluate the endpoints for the efficacy profile.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CAT-8015 20 Microgram Per Kilogram (mcg/kg) | Maximum Plasma Concentration (Cmax) of Moxetumomab Pasudotox | 283 nanogram per milliliter (ng/mL) | Standard Deviation 159 |
| CAT-8015 30 Microgram Per Kilogram (mcg/kg) | Maximum Plasma Concentration (Cmax) of Moxetumomab Pasudotox | 452 nanogram per milliliter (ng/mL) | Standard Deviation 141 |
| CAT-8015 40 Microgram Per Kilogram (mcg/kg) | Maximum Plasma Concentration (Cmax) of Moxetumomab Pasudotox | 589 nanogram per milliliter (ng/mL) | Standard Deviation 366 |
| CAT-8015 50 Microgram Per Kilogram (mcg/kg) | Maximum Plasma Concentration (Cmax) of Moxetumomab Pasudotox | 769 nanogram per milliliter (ng/mL) | Standard Deviation 221 |
| CAT-8015 60 Microgram Per Kilogram (mcg/kg) | Maximum Plasma Concentration (Cmax) of Moxetumomab Pasudotox | 818 nanogram per milliliter (ng/mL) | — |
Secondary
Number of Capillary Leak Syndrome (CLS) Participants With Weight Changes, Albumin, Hypotension, Edema, Hypoxia, and Pulmonary Adverse Events (AEs)
The correlation of CLS and weight changes, albumin, hypotension, edema, hypoxia, and pulmonary AEs were examined.
Time frame: From Screening (Day -28) to Post Therapy Day 30
Population: Safety Population included all participants who received moxetumomab pasudotox. The safety population was used to evaluate baseline characteristics as well as all endpoints for safety.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CAT-8015 20 Microgram Per Kilogram (mcg/kg) | Number of Capillary Leak Syndrome (CLS) Participants With Weight Changes, Albumin, Hypotension, Edema, Hypoxia, and Pulmonary Adverse Events (AEs) | 1 Participants |
| CAT-8015 30 Microgram Per Kilogram (mcg/kg) | Number of Capillary Leak Syndrome (CLS) Participants With Weight Changes, Albumin, Hypotension, Edema, Hypoxia, and Pulmonary Adverse Events (AEs) | 0 Participants |
| CAT-8015 40 Microgram Per Kilogram (mcg/kg) | Number of Capillary Leak Syndrome (CLS) Participants With Weight Changes, Albumin, Hypotension, Edema, Hypoxia, and Pulmonary Adverse Events (AEs) | 1 Participants |
| CAT-8015 50 Microgram Per Kilogram (mcg/kg) | Number of Capillary Leak Syndrome (CLS) Participants With Weight Changes, Albumin, Hypotension, Edema, Hypoxia, and Pulmonary Adverse Events (AEs) | 0 Participants |
| CAT-8015 60 Microgram Per Kilogram (mcg/kg) | Number of Capillary Leak Syndrome (CLS) Participants With Weight Changes, Albumin, Hypotension, Edema, Hypoxia, and Pulmonary Adverse Events (AEs) | 0 Participants |
Secondary
Number of Participants With CD22 Expression Levels
CD22 Expression was analyzed using Prism® analysis. Flow cytometry was performed to quantitate the CD22 expression for the purpose of evaluating the relationship of CD22 expression with response to treatment.
Time frame: Baseline (Day 1) up to End of the Treatment (Last dose of Last cycle) (approximately 3 years)
Population: Evaluable population for expression of CD22 on malignant cells included all participants with peripheral blood samples containing 10 or more B cells (CD19-positive cells) per cubic millimeter.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CAT-8015 20 Microgram Per Kilogram (mcg/kg) | Number of Participants With CD22 Expression Levels | 8 Participants |
| CAT-8015 30 Microgram Per Kilogram (mcg/kg) | Number of Participants With CD22 Expression Levels | 5 Participants |
| CAT-8015 40 Microgram Per Kilogram (mcg/kg) | Number of Participants With CD22 Expression Levels | 2 Participants |
| CAT-8015 50 Microgram Per Kilogram (mcg/kg) | Number of Participants With CD22 Expression Levels | 1 Participants |
Secondary
Number of Participants With Positive Anti-Drug Antibody
The moxetumomab pasudotox specific bridging assay using the Meso Scale Discovery platform was employed to detect anti-drug antibodies (ADA).
Time frame: Baseline (Day 1) up to End of the Treatment (Last dose of Last cycle) (approximately 3 years)
Population: Safety Population included all participants who received moxetumomab pasudotox. The safety population was used to evaluate baseline characteristics as well as all endpoints for safety.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CAT-8015 20 Microgram Per Kilogram (mcg/kg) | Number of Participants With Positive Anti-Drug Antibody | 5 Participants |
| CAT-8015 30 Microgram Per Kilogram (mcg/kg) | Number of Participants With Positive Anti-Drug Antibody | 4 Participants |
| CAT-8015 40 Microgram Per Kilogram (mcg/kg) | Number of Participants With Positive Anti-Drug Antibody | 5 Participants |
| CAT-8015 50 Microgram Per Kilogram (mcg/kg) | Number of Participants With Positive Anti-Drug Antibody | 2 Participants |
| CAT-8015 60 Microgram Per Kilogram (mcg/kg) | Number of Participants With Positive Anti-Drug Antibody | 0 Participants |
Secondary
Percentage of Participants With Complete Response (CR)
The CR rate was defined as the percentage of participants who had achieved CR based on both the evaluable population for efficacy.
Time frame: Baseline (Day 1) until Final Study Visit Post Therapy (up to 2 year after the last participant begins study drug treatment)
Population: Evaluable Population for efficacy included all participants who received any moxetumomab pasudotox treatment and completed at least one post-baseline disease assessment. The Evaluable Population for efficacy was used to evaluate the endpoints for the efficacy profile.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CAT-8015 20 Microgram Per Kilogram (mcg/kg) | Percentage of Participants With Complete Response (CR) | 0 Percentage of Participants |
| CAT-8015 30 Microgram Per Kilogram (mcg/kg) | Percentage of Participants With Complete Response (CR) | 0 Percentage of Participants |
| CAT-8015 40 Microgram Per Kilogram (mcg/kg) | Percentage of Participants With Complete Response (CR) | 0 Percentage of Participants |
| CAT-8015 50 Microgram Per Kilogram (mcg/kg) | Percentage of Participants With Complete Response (CR) | 0 Percentage of Participants |
Secondary
Percentage of Participants With Objective Response (OR)
OR was defined as the percentage of participants with CR or partial response (PR).
Time frame: Baseline (Day 1) until Final Study Visit Post Therapy (up to 2 year after the last participant begins study drug treatment)
Population: Evaluable Population for efficacy included all participants who received any moxetumomab pasudotox treatment and completed at least one post-baseline disease assessment. The Evaluable Population for efficacy was used to evaluate the endpoints for the efficacy profile.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CAT-8015 20 Microgram Per Kilogram (mcg/kg) | Percentage of Participants With Objective Response (OR) | 10 Percentage of Participants |
| CAT-8015 30 Microgram Per Kilogram (mcg/kg) | Percentage of Participants With Objective Response (OR) | 0 Percentage of Participants |
| CAT-8015 40 Microgram Per Kilogram (mcg/kg) | Percentage of Participants With Objective Response (OR) | 0 Percentage of Participants |
| CAT-8015 50 Microgram Per Kilogram (mcg/kg) | Percentage of Participants With Objective Response (OR) | 0 Percentage of Participants |
Secondary
Percentage of Participants With Partial Response (PR)
Time frame: Baseline (Day 1) until Final Study Visit Post Therapy (up to 2 year after the last participant begins study drug treatment)
Population: Evaluable Population for efficacy included all participants who received any moxetumomab pasudotox treatment and completed at least one post-baseline disease assessment. The Evaluable Population for efficacy was used to evaluate the endpoints for the efficacy profile.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CAT-8015 20 Microgram Per Kilogram (mcg/kg) | Percentage of Participants With Partial Response (PR) | 10 Percentage of Participants |
| CAT-8015 30 Microgram Per Kilogram (mcg/kg) | Percentage of Participants With Partial Response (PR) | 0 Percentage of Participants |
| CAT-8015 40 Microgram Per Kilogram (mcg/kg) | Percentage of Participants With Partial Response (PR) | 0 Percentage of Participants |
| CAT-8015 50 Microgram Per Kilogram (mcg/kg) | Percentage of Participants With Partial Response (PR) | 0 Percentage of Participants |
Secondary
Percentage of Participants With Stable Disease (SD)
Time frame: Baseline (Day 1) until Final Study Visit Post Therapy (up to 2 year after the last participant begins study drug treatment)
Population: Evaluable Population for efficacy included all participants who received any moxetumomab pasudotox treatment and completed at least one post-baseline disease assessment. The Evaluable Population for efficacy was used to evaluate the endpoints for the efficacy profile.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CAT-8015 20 Microgram Per Kilogram (mcg/kg) | Percentage of Participants With Stable Disease (SD) | 40.0 Percentage of Participants |
| CAT-8015 30 Microgram Per Kilogram (mcg/kg) | Percentage of Participants With Stable Disease (SD) | 0.0 Percentage of Participants |
| CAT-8015 40 Microgram Per Kilogram (mcg/kg) | Percentage of Participants With Stable Disease (SD) | 100.0 Percentage of Participants |
| CAT-8015 50 Microgram Per Kilogram (mcg/kg) | Percentage of Participants With Stable Disease (SD) | 66.7 Percentage of Participants |
Secondary
Time to Response (TTR)
TTR was measured from the start of moxetumomab pasudotox administration to the first documentation of response (CR or PR) and was only assessed in participants who had achieved objective response (OR).
Time frame: Baseline (Day 1) until Final Study Visit Post Therapy (up to 2 year after the last participant begins study drug treatment)
Population: Evaluable Population for efficacy included all participants who received any moxetumomab pasudotox treatment and completed at least one post-baseline disease assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CAT-8015 20 Microgram Per Kilogram (mcg/kg) | Time to Response (TTR) | 0.79 Months |
| CAT-8015 30 Microgram Per Kilogram (mcg/kg) | Time to Response (TTR) | NA Months |
| CAT-8015 40 Microgram Per Kilogram (mcg/kg) | Time to Response (TTR) | NA Months |
| CAT-8015 50 Microgram Per Kilogram (mcg/kg) | Time to Response (TTR) | NA Months |