Efficacy and Safety Study of CSJ148 in Stem Cell Transplant Patients
Study Details
Study Description
Brief Summary
This study is designed to test if CSJ148 can prevent HCMV replication after stem cell transplantation.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
This study is randomized, double-blinded, and placebo-controlled. 80 Patients will be enrolled and randomized to CSJ148 and placebo in a ratio of 3:1. Patients undergoing stem cell transplantation will be enrolled into the study. The study will consist of a screening period, a baseline visit, approximately 3-month treatment exposure period, an end-of-therapy visit, a follow-up period, and a study completion evaluation approximately 3.5 months after the last dose of study drug is administered.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Cohort 1: CSJ148 Cohort 1: CSJ148 IV q 4weeks |
Biological: CSJ148
CSJ148 IV q 4weeks
|
| Experimental: Cohort 2: CSJ148 Cohort 2: CSJ148 IV q 4weeks |
Biological: CSJ148
CSJ148 IV q 4weeks
|
| Placebo Comparator: Cohort 2: Placebo Cohort 2: Placebo IV q 4weeks |
Drug: Placebo
Placebo IV q 4weeks
|
Outcome Measures
Primary Outcome Measures
- Number of Participants Who Require Preemptive HCMV Therapy [98 days]
Number of participants who require preemptive HCMV therapy. The definition of requiring preemptive anti-HCMV therapy was meeting either one of the following conditions: 1. the plasma HCMV DNA level is >= 1000 copies/mL (with or without HCMV disease) or 2. the plasma HCMV DNA level is < 1000 copies/mL, but HCMV disease was reported
- Number of Participants With Adverse Events as a Measure of Safety and Tolerability [98 days]
Number of participants with adverse events as a measure of safety and tolerability. Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses.
Secondary Outcome Measures
- Time to Start of Preemptive HCMV Therapy Cohort 2 [98 days]
The time to start preemptive therapy is defined as the number of days between initial dose of study drug and the earlier of (1) the start of preemptive therapy, and (2) the development of HCMV disease or death due to HCMV disease, or (3) censored at the EoT visit if no therapy required for Cohort 2
- Number of Times That Preemptive HCMV Therapy is Required -Cohort 2 [98 days]
Among those who required preemptive therapy, the number of times preemptive therapy was required. (Cohort 2)
- Proportion of Participants Developing HCMV Disease [98 days]
Proportion of participants developing HCMV disease
- Area Under the Serum Concentration-time Curve During the Dosing Interval (AUCtau) for CSJ148 Only [Day 1, Day 29, Day 57, Day 85 at predose (0hr) and 3,6,24 hrs post dose]
PK parameters were calculated from plasma concentration-time data using non-compartmental methods. The AUCtau was calculated using a linear trapezoidal method
- Maximum Serum Concentration During the Dosing Interval (Cmax) for CSJ148 Only [Day 1, Day 29, Day 57, Day 85 at predose (0hr) and 3,6,24 hrs post dose]
Cmax is the observed maximum plasma (or serum or blood) concentration following drug administration [ug / mL] for CSJ148 only
- Trough Serum Concentration (Ctrough) for CSJ148 Only [Day 1, Day 29, Day 57, Day 85 at predose (0hr) and 3,6,24 hrs post dose]
Ctrough is The observed plasma (or serum or blood) concentration at the end of a drug administration dosing interval [ug / mL]
- Accumulation Ratio(Racc) for CSJ148 Only at Day 85 [Day 1 and Day 85]
Accumulation ratio(Racc) is Racc: Accumulation ratio, calculated by AUCtau (Day 85) divided by AUCtau (for the 1st dose at Day 1).
- Lambda_z for CSJ148 Only at Day 85 [Day 85]
Lambda_z is the terminal elimination rate constant [1/day] at Day 85
- Half-life (T1/2) for CSJ148 Only at Day 85 [Day 85]
T1/2 is the terminal elimination half-life [time]
Eligibility Criteria
Criteria
Inclusion Criteria:
Patients eligible for inclusion in this study had to fulfill all of the following criteria:
-
Written informed consent must be obtained before any assessment was performed.
-
Male and female patients at least 18 years of age.
-
Patients weighed between 45 -120 kg to participate in the study, and had a body mass index (BMI) within the range of 18 - 34 kg/m2
-
Scheduled to undergo allogeneic bone marrow, peripheral blood stem cell, or cord blood transplantation (transplant may be related or unrelated, T-cell depleted or non-T-cell depleted, myeloablative or non-myeloablative/reduced intensity, haploidentical) and began conditioning chemotherapy within 48 hours of planned dosing day.
-
Patient seropositive for HCMV before transplantation; donor could be seropositive or seronegative for HCMV (donor positive/recipient or donor negative/recipient positive). Historical patient HCMV serology data collected within the last 12 months or local assays could be used to qualify the patient for enrollment.
-
Able to communicate well with the investigator, to understand and comply with the requirements of the study.
Exclusion Criteria:
Patients fulfilling any of the following criteria were not eligible for inclusion in this study:
-
Use of other investigational drugs at the time of enrollment, or within 5 half-lives of enrollment, or until the expected PD (pharmacodynamic) effect has returned to baseline, whichever is longer; or longer if required by local regulations.
-
History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes.
-
Karnofsky performance score <50%.
-
Had HCMV-related organ disease within 6 months prior to enrollment.
-
Detectable HCMV infection (positive pp65 antigenemia or plasma HCMV DNA polymerase chain reaction (PCR) assays prior to enrollment from samples collected within 14 days prior to enrollment. Local assays could be used to qualify the patient for enrollment.
-
Received any of the following within 30 days prior to enrollment: ganciclovir, valganciclovir, foscarnet, cidofovir, acyclovir (>25 mg/kg/day IV), valacyclovir (>3 gm/day oral), famciclovir (>1500 mg/day oral), HCMV immune globulin, immune globulin (>500 mg/kg), or any other medication with anti-HCMV activity.
-
Required mechanical ventilation within 7 days prior to enrollment.
-
Received any vasopressors or other agents for hemodynamic support within 7 days prior to enrollment. These agents included but are not limited to epinephrine, metaraminol, norepinephrine, dopamine, vasopressin, phenylephrine, and dobutamine.
-
Impaired renal function requiring dialysis.
-
Any surgical or medical condition which might increase the risk for thrombotic events if given immunoglobulins. These conditions included cryoglobulinemia, monoclonal gammopathies, and hypertriglyceridemia (fasting level >1000 mg/dL). The investigator should make this determination in consideration of the subject's medical history and laboratory data.
-
Severe liver disease or liver injury as indicated one or more of the following:
-
Alanine aminotransferase (ALT) >5-times the upper limit of normal (ULN).
-
Aspartate aminotransferase (AST) >5-times the upper limit of normal.
-
Gamma-glutamyl transferase (γ-GT) >5-times the upper limit of normal.
-
Serum total bilirubin (TBL) >3-times the upper limit of normal.
-
Pregnant or nursing (lactating) women, where pregnancy was defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test.
-
Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they were using effective methods of contraception during dosing of study treatment.
Effective contraception methods included:
-
Total abstinence (when this is in line with the preferred and usual lifestyle of the subject). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
-
Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman was confirmed by follow up hormone level assessment.
-
Male sterilization (at least 6 months prior to screening). For female patients on the study, the vasectomized male partner should be the sole partner for that subject.
-
Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/ vaginal suppository.
-
Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception.
-
Placement of an intrauterine device (IUD) or intrauterine system (IUS). In case of use of oral contraception women would have been stable on the same pill for a minimum of 3 months before taking study treatment. Women were considered post-menopausal and not of child bearing potential if they had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age appropriate, history of vasomotor symptoms) or had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman had been confirmed by follow up hormone level assessment was she considered not of child bearing potential.
- History of positive HIV (ELISA and Western blot) test result. Testing was not required. No additional exclusions were applied by the investigator, in order to ensure that the study population was representative of all eligible patients.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Novartis Investigative Site | San Francisco | California | United States | 94143 |
| 2 | Novartis Investigative Site | Gainesville | Florida | United States | 32610 |
| 3 | Novartis Investigative Site | Beech Grove | Indiana | United States | 46107 |
| 4 | Novartis Investigative Site | Durham | North Carolina | United States | 27710 |
| 5 | Novartis Investigative Site | Houston | Texas | United States | 77030 |
| 6 | Novartis Investigative Site | Leuven | Belgium | 3000 | |
| 7 | Novartis Investigative Site | Erlangen | Germany | 91054 | |
| 8 | Novartis Investigative Site | Essen | Germany | 45147 | |
| 9 | Novartis Investigative Site | Regensburg | Germany | 93053 | |
| 10 | Novartis Investigative Site | Wuerzburg | Germany | 97070 | |
| 11 | Novartis Investigative Site | Seoul | Korea | Korea, Republic of | 06351 |
| 12 | Novartis Investigative Site | Seoul | Korea, Republic of | 06591 | |
| 13 | Novartis Investigative Site | Singapore | Singapore | 119228 | |
| 14 | Novartis Investigative Site | Singapore | Singapore | 169608 | |
| 15 | Novartis Investigative Site | New Taipei | Taiwan | 33305 | |
| 16 | Novartis Investigative Site | Taichung | Taiwan | 40447 | |
| 17 | Novartis Investigative Site | Taipei | Taiwan | 10002 |
Sponsors and Collaborators
- Novartis Pharmaceuticals
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- CCSJ148X2201
Study Results
Participant Flow
| Recruitment Details | Cohort 1: Six patients were planned for enrollment; 6 patients were enrolled. Cohort 2: Eighty patients were planned and 80 were enrolled. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Cohort 1: CSJ148 | Cohort 2: CSJ148 | Cohort 2: Placebo |
|---|---|---|---|
| Arm/Group Description | Cohort 1: CSJ148 IV q 4weeks | Cohort 2: CSJ148 IV q 4weeks | Cohort 2: Placebo IV q 4weeks |
| Period Title: Overall Study | |||
| STARTED | 6 | 59 | 21 |
| PD Analysis Set (Cohort 2) | 0 | 42 | 17 |
| COMPLETED | 5 | 38 | 16 |
| NOT COMPLETED | 1 | 21 | 5 |
Baseline Characteristics
| Arm/Group Title | Cohort 1: CSJ148 | Cohort 2: CSJ148 | Cohort 2: Placebo | Total |
|---|---|---|---|---|
| Arm/Group Description | Cohort 1: CSJ148 IV q 4weeks | Cohort 2: CSJ148 IV q 4weeks | Cohort 2: Placebo IV q 4weeks | Total of all reporting groups |
| Overall Participants | 6 | 59 | 21 | 86 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
52.8
(8.70)
|
54.7
(12.33)
|
46.0
(14.33)
|
52.5
(13.04)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
2
33.3%
|
23
39%
|
6
28.6%
|
31
36%
|
| Male |
4
66.7%
|
36
61%
|
15
71.4%
|
55
64%
|
Outcome Measures
| Title | Number of Participants Who Require Preemptive HCMV Therapy |
|---|---|
| Description | Number of participants who require preemptive HCMV therapy. The definition of requiring preemptive anti-HCMV therapy was meeting either one of the following conditions: 1. the plasma HCMV DNA level is >= 1000 copies/mL (with or without HCMV disease) or 2. the plasma HCMV DNA level is < 1000 copies/mL, but HCMV disease was reported |
| Time Frame | 98 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set - included all 86 patients enrolled in the study |
| Arm/Group Title | Total CSJ148 (Cohort 1 & Cohort 2) | Cohort 2: CSJ148 | Cohort 2: Placebo |
|---|---|---|---|
| Arm/Group Description | Cohort 1: CSJ148 IV q 4weeks and Cohort 2: CSJ148 IV q 4weeks | Cohort 2: CSJ148 IV q 4weeks | Cohort 2: Placebo IV q 4weeks |
| Measure Participants | 65 | 59 | 21 |
| Number [Count of Participants] |
24
400%
|
23
39%
|
9
42.9%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Total CSJ148 (Cohort 1 & Cohort 2), Cohort 2: Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
| Estimated Value | 0.891 | |
| Confidence Interval |
(2-Sided) 90% 0.606 to 1.305 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: CSJ148, Cohort 2: Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
| Estimated Value | 0.941 | |
| Confidence Interval |
(2-Sided) 90% 0.639 to 1.377 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Number of Participants With Adverse Events as a Measure of Safety and Tolerability |
|---|---|
| Description | Number of participants with adverse events as a measure of safety and tolerability. Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses. |
| Time Frame | 98 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set- Eighty-six patients were enrolled in the study and all were included in the safety analysis set |
| Arm/Group Title | Total CSJ148 (Cohort 1 & Cohort 2) | Cohort 2: Placebo |
|---|---|---|
| Arm/Group Description | Cohort 1: CSJ148 IV q 4weeks & Cohort 2: CSJ148 IV q 4 weeks | Cohort 2: Placebo IV q 4weeks |
| Measure Participants | 65 | 21 |
| At least one treatment-emergent AE |
65
1083.3%
|
21
35.6%
|
| At least one drug-related AE |
0
0%
|
2
3.4%
|
| At least one SAE |
46
766.7%
|
15
25.4%
|
| At least one drug-related SAE |
0
0%
|
1
1.7%
|
| Deaths |
12
200%
|
0
0%
|
| At least 1 treatment-emergent AE grade 3 or higher |
58
966.7%
|
17
28.8%
|
| Total deaths:those reported after study completion |
19
316.7%
|
3
5.1%
|
| Discontinued study treatment due to any AE |
1
16.7%
|
1
1.7%
|
| Title | Time to Start of Preemptive HCMV Therapy Cohort 2 |
|---|---|
| Description | The time to start preemptive therapy is defined as the number of days between initial dose of study drug and the earlier of (1) the start of preemptive therapy, and (2) the development of HCMV disease or death due to HCMV disease, or (3) censored at the EoT visit if no therapy required for Cohort 2 |
| Time Frame | 98 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| PD analysis set (Cohort 2) -included 59 patients, 27 patients (31%) were excluded. |
| Arm/Group Title | Cohort 2: CSJ148 | Cohort 2: Placebo |
|---|---|---|
| Arm/Group Description | Cohort 2: CSJ148 IV q 4weeks | Cohort 2: Placebo IV q 4weeks |
| Measure Participants | 42 | 17 |
| Mean (Standard Deviation) [days] |
62.03
(12.145)
|
49.54
(13.470)
|
| Title | Number of Times That Preemptive HCMV Therapy is Required -Cohort 2 |
|---|---|
| Description | Among those who required preemptive therapy, the number of times preemptive therapy was required. (Cohort 2) |
| Time Frame | 98 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| PD analysis set (Cohort 2) -included 59 patients, 27 patients (31%) were excluded. |
| Arm/Group Title | Cohort 2: CSJ148 | Cohort 2: Placebo |
|---|---|---|
| Arm/Group Description | Cohort 2: CSJ148 IV q 4weeks | Cohort 2: Placebo IV q 4weeks |
| Measure Participants | 42 | 17 |
| Least Squares Mean (90% Confidence Interval) [number of times] |
2.070
|
2.540
|
| Title | Proportion of Participants Developing HCMV Disease |
|---|---|
| Description | Proportion of participants developing HCMV disease |
| Time Frame | 98 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| PD analysis set (Cohort 2) -included 59 patients, 27 patients (31%) were excluded. |
| Arm/Group Title | Cohort 2: CSJ148 | Cohort 2: Placebo |
|---|---|---|
| Arm/Group Description | Cohort 2: CSJ148 IV q 4weeks | Cohort 2: Placebo IV q 4weeks |
| Measure Participants | 42 | 17 |
| Number (90% Confidence Interval) [proportion of participants] |
0.119
2%
|
0
0%
|
| Title | Area Under the Serum Concentration-time Curve During the Dosing Interval (AUCtau) for CSJ148 Only |
|---|---|
| Description | PK parameters were calculated from plasma concentration-time data using non-compartmental methods. The AUCtau was calculated using a linear trapezoidal method |
| Time Frame | Day 1, Day 29, Day 57, Day 85 at predose (0hr) and 3,6,24 hrs post dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetics (PK) analysis set (CSJ148 only)- The PK analysis set included the 65 patients who received a dose of CSJ148 |
| Arm/Group Title | Total CSJ148 (Cohort 1 & Cohort 2) |
|---|---|
| Arm/Group Description | Cohort 1: CSJ148 IV q 4weeks and Cohort 2: CSJ148 IV q 4weeks |
| Measure Participants | 65 |
| Day 1 |
7310
(2310)
|
| Day 29 |
9890
(3470)
|
| Day 57 |
11400
(4020)
|
| Day 85 |
12900
(4380)
|
| Title | Maximum Serum Concentration During the Dosing Interval (Cmax) for CSJ148 Only |
|---|---|
| Description | Cmax is the observed maximum plasma (or serum or blood) concentration following drug administration [ug / mL] for CSJ148 only |
| Time Frame | Day 1, Day 29, Day 57, Day 85 at predose (0hr) and 3,6,24 hrs post dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetics (PK) analysis set (CSJ148 only)- The PK analysis set included the 65 patients who received a dose of CSJ148 |
| Arm/Group Title | Total CSJ148 (Cohort 1 & Cohort 2) |
|---|---|
| Arm/Group Description | Cohort 1: CSJ148 IV q 4weeks and Cohort 2: CSJ148 IV q 4weeks |
| Measure Participants | 65 |
| Day 1 |
1040
(356)
|
| Day 29 |
1100
(282)
|
| Day 57 |
1180
(316)
|
| Day 85 |
1230
(458)
|
| Title | Trough Serum Concentration (Ctrough) for CSJ148 Only |
|---|---|
| Description | Ctrough is The observed plasma (or serum or blood) concentration at the end of a drug administration dosing interval [ug / mL] |
| Time Frame | Day 1, Day 29, Day 57, Day 85 at predose (0hr) and 3,6,24 hrs post dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetics (PK) analysis set (CSJ148 only)- The PK analysis set included the 65 patients who received a dose of CSJ148 |
| Arm/Group Title | Total CSJ148 (Cohort 1 & Cohort 2) |
|---|---|
| Arm/Group Description | Cohort 1: CSJ148 IV q 4weeks and Cohort 2: CSJ148 IV q 4weeks |
| Measure Participants | 65 |
| Day 1 |
104
(59.7)
|
| Day 29 |
167
(85.5)
|
| Day 57 |
214
(152)
|
| Day 85 |
223
(104)
|
| Title | Accumulation Ratio(Racc) for CSJ148 Only at Day 85 |
|---|---|
| Description | Accumulation ratio(Racc) is Racc: Accumulation ratio, calculated by AUCtau (Day 85) divided by AUCtau (for the 1st dose at Day 1). |
| Time Frame | Day 1 and Day 85 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetics (PK) analysis set (CSJ148 only)- The PK analysis set included the 65 patients who received a dose of CSJ148 |
| Arm/Group Title | Total CSJ148 (Cohort 1 & Cohort 2) |
|---|---|
| Arm/Group Description | Cohort 1: CSJ148 IV q 4weeks and Cohort 2: CSJ148 IV q 4weeks |
| Measure Participants | 65 |
| Mean (Standard Deviation) [Ratio] |
1.83
(0.531)
|
| Title | Lambda_z for CSJ148 Only at Day 85 |
|---|---|
| Description | Lambda_z is the terminal elimination rate constant [1/day] at Day 85 |
| Time Frame | Day 85 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetics (PK) analysis set (CSJ148 only)- The PK analysis set included the 65 patients who received a dose of CSJ148 |
| Arm/Group Title | Total CSJ148 (Cohort 1 & Cohort 2) |
|---|---|
| Arm/Group Description | Cohort 1: CSJ148 IV q 4weeks and Cohort 2: CSJ148 IV q 4weeks |
| Measure Participants | 65 |
| Mean (Standard Deviation) [1/day] |
0.0409
(0.0175)
|
| Title | Half-life (T1/2) for CSJ148 Only at Day 85 |
|---|---|
| Description | T1/2 is the terminal elimination half-life [time] |
| Time Frame | Day 85 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetics (PK) analysis set (CSJ148 only)- The PK analysis set included the 65 patients who received a dose of CSJ148 |
| Arm/Group Title | Total CSJ148 (Cohort 1 & Cohort 2) |
|---|---|
| Arm/Group Description | Cohort 1: CSJ148 IV q 4weeks and Cohort 2: CSJ148 IV q 4weeks |
| Measure Participants | 65 |
| Mean (Standard Deviation) [day] |
19.7
(7.18)
|
Adverse Events
| Time Frame | Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients. | |||
| Arm/Group Title | Placebo | Total CSJ148 | ||
| Arm/Group Description | Cohort 2: Placebo IV q 4weeks | Cohort 1: CSJ148 IV q 4weeks & Cohort 2: CSJ148 IV q 4weeks | ||
All Cause Mortality |
||||
| Placebo | Total CSJ148 | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Placebo | Total CSJ148 | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 15/21 (71.4%) | 46/65 (70.8%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 0/21 (0%) | 1/65 (1.5%) | ||
| Febrile neutropenia | 1/21 (4.8%) | 8/65 (12.3%) | ||
| Microangiopathic haemolytic anaemia | 0/21 (0%) | 1/65 (1.5%) | ||
| Neutropenia | 0/21 (0%) | 1/65 (1.5%) | ||
| Splenic lesion | 0/21 (0%) | 1/65 (1.5%) | ||
| Thrombocytopenia | 1/21 (4.8%) | 1/65 (1.5%) | ||
| Thrombotic microangiopathy | 0/21 (0%) | 1/65 (1.5%) | ||
| Thrombotic thrombocytopenic purpura | 0/21 (0%) | 1/65 (1.5%) | ||
| Cardiac disorders | ||||
| Atrial fibrillation | 0/21 (0%) | 1/65 (1.5%) | ||
| Atrial flutter | 0/21 (0%) | 2/65 (3.1%) | ||
| Bradycardia | 1/21 (4.8%) | 0/65 (0%) | ||
| Cardiac tamponade | 0/21 (0%) | 1/65 (1.5%) | ||
| Intracardiac mass | 0/21 (0%) | 1/65 (1.5%) | ||
| Gastrointestinal disorders | ||||
| Abdominal discomfort | 0/21 (0%) | 1/65 (1.5%) | ||
| Abdominal pain | 0/21 (0%) | 1/65 (1.5%) | ||
| Abdominal pain upper | 0/21 (0%) | 2/65 (3.1%) | ||
| Ascites | 0/21 (0%) | 1/65 (1.5%) | ||
| Colitis erosive | 1/21 (4.8%) | 0/65 (0%) | ||
| Diarrhoea | 1/21 (4.8%) | 2/65 (3.1%) | ||
| Gastrointestinal haemorrhage | 0/21 (0%) | 2/65 (3.1%) | ||
| Haematemesis | 0/21 (0%) | 1/65 (1.5%) | ||
| Haemorrhoids | 1/21 (4.8%) | 0/65 (0%) | ||
| Ileus | 0/21 (0%) | 1/65 (1.5%) | ||
| Large intestinal ulcer | 1/21 (4.8%) | 0/65 (0%) | ||
| Nausea | 0/21 (0%) | 2/65 (3.1%) | ||
| Oedematous pancreatitis | 0/21 (0%) | 1/65 (1.5%) | ||
| Pancreatitis acute | 0/21 (0%) | 1/65 (1.5%) | ||
| Rectal haemorrhage | 0/21 (0%) | 1/65 (1.5%) | ||
| Rectal lesion | 0/21 (0%) | 1/65 (1.5%) | ||
| Upper gastrointestinal haemorrhage | 0/21 (0%) | 1/65 (1.5%) | ||
| Vomiting | 0/21 (0%) | 2/65 (3.1%) | ||
| General disorders | ||||
| Non-cardiac chest pain | 0/21 (0%) | 3/65 (4.6%) | ||
| Oedema peripheral | 0/21 (0%) | 1/65 (1.5%) | ||
| Pyrexia | 2/21 (9.5%) | 2/65 (3.1%) | ||
| Hepatobiliary disorders | ||||
| Cholecystitis acute | 0/21 (0%) | 1/65 (1.5%) | ||
| Hepatic function abnormal | 1/21 (4.8%) | 0/65 (0%) | ||
| Hepatic lesion | 0/21 (0%) | 1/65 (1.5%) | ||
| Hepatitis cholestatic | 0/21 (0%) | 1/65 (1.5%) | ||
| Hyperbilirubinaemia | 1/21 (4.8%) | 0/65 (0%) | ||
| Immune system disorders | ||||
| Acute graft versus host disease | 2/21 (9.5%) | 9/65 (13.8%) | ||
| Acute graft versus host disease in liver | 0/21 (0%) | 1/65 (1.5%) | ||
| Acute graft versus host disease in skin | 1/21 (4.8%) | 1/65 (1.5%) | ||
| Anaphylactic shock | 0/21 (0%) | 1/65 (1.5%) | ||
| Chronic graft versus host disease in liver | 0/21 (0%) | 1/65 (1.5%) | ||
| Infections and infestations | ||||
| Atypical pneumonia | 1/21 (4.8%) | 1/65 (1.5%) | ||
| Bacteraemia | 0/21 (0%) | 1/65 (1.5%) | ||
| Bacteriuria | 0/21 (0%) | 1/65 (1.5%) | ||
| Clostridium difficile colitis | 0/21 (0%) | 1/65 (1.5%) | ||
| Cytomegalovirus chorioretinitis | 1/21 (4.8%) | 0/65 (0%) | ||
| Cytomegalovirus colitis | 0/21 (0%) | 2/65 (3.1%) | ||
| Cytomegalovirus gastritis | 0/21 (0%) | 1/65 (1.5%) | ||
| Cytomegalovirus infection | 0/21 (0%) | 2/65 (3.1%) | ||
| Cytomegalovirus viraemia | 2/21 (9.5%) | 2/65 (3.1%) | ||
| Disseminated tuberculosis | 1/21 (4.8%) | 0/65 (0%) | ||
| Enterobacter bacteraemia | 0/21 (0%) | 1/65 (1.5%) | ||
| Epididymitis tuberculous | 0/21 (0%) | 1/65 (1.5%) | ||
| Epstein-Barr virus infection | 0/21 (0%) | 2/65 (3.1%) | ||
| Escherichia bacteraemia | 0/21 (0%) | 1/65 (1.5%) | ||
| Escherichia sepsis | 0/21 (0%) | 1/65 (1.5%) | ||
| Herpes zoster | 0/21 (0%) | 2/65 (3.1%) | ||
| Human herpesvirus 6 infection | 0/21 (0%) | 1/65 (1.5%) | ||
| JC virus infection | 1/21 (4.8%) | 0/65 (0%) | ||
| Klebsiella infection | 1/21 (4.8%) | 0/65 (0%) | ||
| Meningoencephalitis herpetic | 0/21 (0%) | 1/65 (1.5%) | ||
| Ophthalmic herpes zoster | 0/21 (0%) | 1/65 (1.5%) | ||
| Pneumonia | 1/21 (4.8%) | 5/65 (7.7%) | ||
| Pneumonia bacterial | 0/21 (0%) | 1/65 (1.5%) | ||
| Pneumonia fungal | 1/21 (4.8%) | 1/65 (1.5%) | ||
| Pseudomonal bacteraemia | 0/21 (0%) | 1/65 (1.5%) | ||
| Pseudomonal sepsis | 0/21 (0%) | 1/65 (1.5%) | ||
| Pseudomonas infection | 0/21 (0%) | 1/65 (1.5%) | ||
| Pulmonary tuberculosis | 1/21 (4.8%) | 0/65 (0%) | ||
| Respiratory syncytial virus infection | 1/21 (4.8%) | 0/65 (0%) | ||
| Rhinovirus infection | 1/21 (4.8%) | 0/65 (0%) | ||
| Sepsis | 2/21 (9.5%) | 4/65 (6.2%) | ||
| Septic shock | 0/21 (0%) | 3/65 (4.6%) | ||
| Sinusitis | 1/21 (4.8%) | 0/65 (0%) | ||
| Staphylococcal sepsis | 0/21 (0%) | 2/65 (3.1%) | ||
| Stenotrophomonas infection | 0/21 (0%) | 1/65 (1.5%) | ||
| Upper respiratory tract infection | 0/21 (0%) | 1/65 (1.5%) | ||
| Urinary tract infection | 0/21 (0%) | 2/65 (3.1%) | ||
| Injury, poisoning and procedural complications | ||||
| Engraft failure | 0/21 (0%) | 1/65 (1.5%) | ||
| Fall | 0/21 (0%) | 1/65 (1.5%) | ||
| Hip fracture | 1/21 (4.8%) | 0/65 (0%) | ||
| Transplant failure | 0/21 (0%) | 1/65 (1.5%) | ||
| Investigations | ||||
| Alanine aminotransferase increased | 1/21 (4.8%) | 2/65 (3.1%) | ||
| Aspartate aminotransferase increased | 1/21 (4.8%) | 1/65 (1.5%) | ||
| Blood bilirubin increased | 0/21 (0%) | 2/65 (3.1%) | ||
| Blood lactate dehydrogenase increased | 1/21 (4.8%) | 0/65 (0%) | ||
| Cytomegalovirus test positive | 1/21 (4.8%) | 0/65 (0%) | ||
| Gamma-glutamyltransferase increased | 1/21 (4.8%) | 0/65 (0%) | ||
| Lipase increased | 1/21 (4.8%) | 0/65 (0%) | ||
| Metabolism and nutrition disorders | ||||
| Dehydration | 0/21 (0%) | 1/65 (1.5%) | ||
| Hypophagia | 0/21 (0%) | 1/65 (1.5%) | ||
| Malnutrition | 1/21 (4.8%) | 0/65 (0%) | ||
| Metabolic acidosis | 0/21 (0%) | 1/65 (1.5%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Muscular weakness | 0/21 (0%) | 1/65 (1.5%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Acute myeloid leukaemia recurrent | 2/21 (9.5%) | 4/65 (6.2%) | ||
| Chronic myeloid leukaemia recurrent | 0/21 (0%) | 1/65 (1.5%) | ||
| Chronic myelomonocytic leukaemia | 0/21 (0%) | 1/65 (1.5%) | ||
| Post transplant lymphoproliferative disorder | 1/21 (4.8%) | 1/65 (1.5%) | ||
| Prostate cancer metastatic | 0/21 (0%) | 1/65 (1.5%) | ||
| Prostate cancer recurrent | 0/21 (0%) | 1/65 (1.5%) | ||
| T-cell lymphoma recurrent | 0/21 (0%) | 1/65 (1.5%) | ||
| Nervous system disorders | ||||
| Facial paresis | 0/21 (0%) | 1/65 (1.5%) | ||
| Metabolic encephalopathy | 0/21 (0%) | 1/65 (1.5%) | ||
| Posterior reversible encephalopathy syndrome | 0/21 (0%) | 1/65 (1.5%) | ||
| Somnolence | 0/21 (0%) | 1/65 (1.5%) | ||
| Psychiatric disorders | ||||
| Hallucination | 0/21 (0%) | 1/65 (1.5%) | ||
| Mental status changes | 0/21 (0%) | 1/65 (1.5%) | ||
| Renal and urinary disorders | ||||
| Acute kidney injury | 1/21 (4.8%) | 4/65 (6.2%) | ||
| Renal disorder | 0/21 (0%) | 1/65 (1.5%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Acute respiratory failure | 0/21 (0%) | 4/65 (6.2%) | ||
| Asthma | 1/21 (4.8%) | 0/65 (0%) | ||
| Dyspnoea | 0/21 (0%) | 1/65 (1.5%) | ||
| Haemothorax | 0/21 (0%) | 1/65 (1.5%) | ||
| Pleural effusion | 0/21 (0%) | 1/65 (1.5%) | ||
| Respiratory distress | 0/21 (0%) | 1/65 (1.5%) | ||
| Respiratory failure | 1/21 (4.8%) | 3/65 (4.6%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Dermatitis bullous | 0/21 (0%) | 1/65 (1.5%) | ||
| Rash | 0/21 (0%) | 1/65 (1.5%) | ||
| Rash erythematous | 0/21 (0%) | 1/65 (1.5%) | ||
| Skin lesion | 0/21 (0%) | 1/65 (1.5%) | ||
| Vascular disorders | ||||
| Hypertension | 0/21 (0%) | 2/65 (3.1%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Placebo | Total CSJ148 | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 21/21 (100%) | 65/65 (100%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 4/21 (19%) | 6/65 (9.2%) | ||
| Febrile neutropenia | 10/21 (47.6%) | 25/65 (38.5%) | ||
| Neutropenia | 5/21 (23.8%) | 6/65 (9.2%) | ||
| Thrombocytopenia | 3/21 (14.3%) | 9/65 (13.8%) | ||
| Cardiac disorders | ||||
| Tachycardia | 2/21 (9.5%) | 8/65 (12.3%) | ||
| Eye disorders | ||||
| Dry eye | 5/21 (23.8%) | 14/65 (21.5%) | ||
| Gastrointestinal disorders | ||||
| Abdominal discomfort | 1/21 (4.8%) | 6/65 (9.2%) | ||
| Abdominal distension | 3/21 (14.3%) | 6/65 (9.2%) | ||
| Abdominal pain | 5/21 (23.8%) | 16/65 (24.6%) | ||
| Abdominal pain upper | 5/21 (23.8%) | 5/65 (7.7%) | ||
| Constipation | 8/21 (38.1%) | 19/65 (29.2%) | ||
| Diarrhoea | 12/21 (57.1%) | 43/65 (66.2%) | ||
| Dry mouth | 3/21 (14.3%) | 11/65 (16.9%) | ||
| Dyspepsia | 3/21 (14.3%) | 7/65 (10.8%) | ||
| Epigastric discomfort | 2/21 (9.5%) | 2/65 (3.1%) | ||
| Gastrointestinal inflammation | 0/21 (0%) | 8/65 (12.3%) | ||
| Gastrooesophageal reflux disease | 0/21 (0%) | 6/65 (9.2%) | ||
| Haemorrhoids | 2/21 (9.5%) | 13/65 (20%) | ||
| Lip dry | 2/21 (9.5%) | 1/65 (1.5%) | ||
| Melaena | 0/21 (0%) | 4/65 (6.2%) | ||
| Mouth haemorrhage | 2/21 (9.5%) | 3/65 (4.6%) | ||
| Nausea | 14/21 (66.7%) | 45/65 (69.2%) | ||
| Oesophagitis | 1/21 (4.8%) | 9/65 (13.8%) | ||
| Stomatitis | 15/21 (71.4%) | 36/65 (55.4%) | ||
| Tongue ulceration | 2/21 (9.5%) | 1/65 (1.5%) | ||
| Vomiting | 14/21 (66.7%) | 38/65 (58.5%) | ||
| General disorders | ||||
| Asthenia | 2/21 (9.5%) | 7/65 (10.8%) | ||
| Catheter site erythema | 2/21 (9.5%) | 4/65 (6.2%) | ||
| Catheter site pain | 1/21 (4.8%) | 6/65 (9.2%) | ||
| Chest discomfort | 1/21 (4.8%) | 5/65 (7.7%) | ||
| Chills | 4/21 (19%) | 15/65 (23.1%) | ||
| Fatigue | 7/21 (33.3%) | 18/65 (27.7%) | ||
| Generalised oedema | 0/21 (0%) | 7/65 (10.8%) | ||
| Non-cardiac chest pain | 1/21 (4.8%) | 8/65 (12.3%) | ||
| Oedema peripheral | 2/21 (9.5%) | 12/65 (18.5%) | ||
| Pain | 0/21 (0%) | 6/65 (9.2%) | ||
| Pyrexia | 10/21 (47.6%) | 38/65 (58.5%) | ||
| Hepatobiliary disorders | ||||
| Hyperbilirubinaemia | 2/21 (9.5%) | 4/65 (6.2%) | ||
| Immune system disorders | ||||
| Acute graft versus host disease | 3/21 (14.3%) | 10/65 (15.4%) | ||
| Acute graft versus host disease in intestine | 0/21 (0%) | 4/65 (6.2%) | ||
| Acute graft versus host disease in skin | 3/21 (14.3%) | 14/65 (21.5%) | ||
| Chronic graft versus host disease | 4/21 (19%) | 6/65 (9.2%) | ||
| Chronic graft versus host disease in skin | 1/21 (4.8%) | 5/65 (7.7%) | ||
| Infections and infestations | ||||
| Candida infection | 0/21 (0%) | 5/65 (7.7%) | ||
| Clostridium difficile infection | 0/21 (0%) | 5/65 (7.7%) | ||
| Device related infection | 2/21 (9.5%) | 3/65 (4.6%) | ||
| Folliculitis | 2/21 (9.5%) | 7/65 (10.8%) | ||
| Herpes zoster | 2/21 (9.5%) | 4/65 (6.2%) | ||
| Human herpesvirus 6 infection | 1/21 (4.8%) | 4/65 (6.2%) | ||
| Oral candidiasis | 3/21 (14.3%) | 5/65 (7.7%) | ||
| Oral herpes | 1/21 (4.8%) | 4/65 (6.2%) | ||
| Papilloma viral infection | 2/21 (9.5%) | 0/65 (0%) | ||
| Pneumonia | 0/21 (0%) | 4/65 (6.2%) | ||
| Rhinovirus infection | 2/21 (9.5%) | 1/65 (1.5%) | ||
| Staphylococcal bacteraemia | 3/21 (14.3%) | 5/65 (7.7%) | ||
| Upper respiratory tract infection | 4/21 (19%) | 8/65 (12.3%) | ||
| Urinary tract infection | 1/21 (4.8%) | 5/65 (7.7%) | ||
| Injury, poisoning and procedural complications | ||||
| Fall | 0/21 (0%) | 6/65 (9.2%) | ||
| Skin abrasion | 0/21 (0%) | 4/65 (6.2%) | ||
| Transfusion reaction | 1/21 (4.8%) | 5/65 (7.7%) | ||
| Investigations | ||||
| Alanine aminotransferase increased | 2/21 (9.5%) | 5/65 (7.7%) | ||
| Aspartate aminotransferase increased | 1/21 (4.8%) | 4/65 (6.2%) | ||
| Blood bilirubin increased | 1/21 (4.8%) | 7/65 (10.8%) | ||
| Blood creatinine increased | 3/21 (14.3%) | 8/65 (12.3%) | ||
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 7/21 (33.3%) | 27/65 (41.5%) | ||
| Fluid overload | 1/21 (4.8%) | 5/65 (7.7%) | ||
| Hyperglycaemia | 1/21 (4.8%) | 8/65 (12.3%) | ||
| Hyperkalaemia | 1/21 (4.8%) | 6/65 (9.2%) | ||
| Hypocalcaemia | 1/21 (4.8%) | 7/65 (10.8%) | ||
| Hypokalaemia | 5/21 (23.8%) | 20/65 (30.8%) | ||
| Hypomagnesaemia | 4/21 (19%) | 9/65 (13.8%) | ||
| Hypophosphataemia | 3/21 (14.3%) | 6/65 (9.2%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 1/21 (4.8%) | 12/65 (18.5%) | ||
| Back pain | 5/21 (23.8%) | 17/65 (26.2%) | ||
| Bone pain | 1/21 (4.8%) | 9/65 (13.8%) | ||
| Musculoskeletal pain | 0/21 (0%) | 4/65 (6.2%) | ||
| Myalgia | 1/21 (4.8%) | 7/65 (10.8%) | ||
| Pain in extremity | 2/21 (9.5%) | 5/65 (7.7%) | ||
| Nervous system disorders | ||||
| Dizziness | 3/21 (14.3%) | 16/65 (24.6%) | ||
| Headache | 6/21 (28.6%) | 24/65 (36.9%) | ||
| Neuropathy peripheral | 1/21 (4.8%) | 6/65 (9.2%) | ||
| Syncope | 0/21 (0%) | 4/65 (6.2%) | ||
| Tremor | 1/21 (4.8%) | 4/65 (6.2%) | ||
| Psychiatric disorders | ||||
| Anxiety | 0/21 (0%) | 5/65 (7.7%) | ||
| Confusional state | 0/21 (0%) | 7/65 (10.8%) | ||
| Hallucination | 0/21 (0%) | 5/65 (7.7%) | ||
| Insomnia | 6/21 (28.6%) | 15/65 (23.1%) | ||
| Sleep disorder | 2/21 (9.5%) | 1/65 (1.5%) | ||
| Renal and urinary disorders | ||||
| Acute kidney injury | 1/21 (4.8%) | 5/65 (7.7%) | ||
| Chronic kidney disease | 2/21 (9.5%) | 0/65 (0%) | ||
| Dysuria | 2/21 (9.5%) | 5/65 (7.7%) | ||
| Haematuria | 1/21 (4.8%) | 10/65 (15.4%) | ||
| Pollakiuria | 2/21 (9.5%) | 8/65 (12.3%) | ||
| Reproductive system and breast disorders | ||||
| Scrotal pain | 2/21 (9.5%) | 0/65 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 9/21 (42.9%) | 25/65 (38.5%) | ||
| Dyspnoea | 3/21 (14.3%) | 13/65 (20%) | ||
| Epistaxis | 2/21 (9.5%) | 8/65 (12.3%) | ||
| Haemoptysis | 0/21 (0%) | 4/65 (6.2%) | ||
| Hiccups | 2/21 (9.5%) | 4/65 (6.2%) | ||
| Hypoxia | 0/21 (0%) | 7/65 (10.8%) | ||
| Nasal congestion | 2/21 (9.5%) | 4/65 (6.2%) | ||
| Oropharyngeal pain | 3/21 (14.3%) | 12/65 (18.5%) | ||
| Pharyngeal inflammation | 1/21 (4.8%) | 5/65 (7.7%) | ||
| Pleural effusion | 1/21 (4.8%) | 9/65 (13.8%) | ||
| Productive cough | 1/21 (4.8%) | 4/65 (6.2%) | ||
| Rhinorrhoea | 3/21 (14.3%) | 3/65 (4.6%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Blister | 0/21 (0%) | 4/65 (6.2%) | ||
| Decubitus ulcer | 0/21 (0%) | 5/65 (7.7%) | ||
| Dry skin | 4/21 (19%) | 6/65 (9.2%) | ||
| Eczema | 2/21 (9.5%) | 1/65 (1.5%) | ||
| Erythema | 3/21 (14.3%) | 4/65 (6.2%) | ||
| Petechiae | 1/21 (4.8%) | 4/65 (6.2%) | ||
| Pruritus | 4/21 (19%) | 18/65 (27.7%) | ||
| Rash | 7/21 (33.3%) | 24/65 (36.9%) | ||
| Rash generalised | 2/21 (9.5%) | 1/65 (1.5%) | ||
| Rash macular | 2/21 (9.5%) | 1/65 (1.5%) | ||
| Urticaria | 2/21 (9.5%) | 6/65 (9.2%) | ||
| Vascular disorders | ||||
| Hypertension | 5/21 (23.8%) | 23/65 (35.4%) | ||
| Hypotension | 4/21 (19%) | 9/65 (13.8%) | ||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single- site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | Novartis Pharmaceuticals |
| Phone | 8627788300 |
- CCSJ148X2201