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NCT02268526

Efficacy and Safety Study of CSJ148 in Stem Cell Transplant Patients

Completed Phase 2 Results posted Last updated 5 January 2021
What this trial tests

Phase 2 trial testing CSJ148 in HCMV in 86 participants. Completed in 7 December 2016.

Timeline
2 June 2015
Primary endpoint
7 December 2016
7 December 2016

Quick facts

Lead sponsorNovartis Pharmaceuticals
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingtriple
Primary purposeprevention
Enrollment86
Start date2 June 2015
Primary completion7 December 2016
Estimated completion7 December 2016
Sites17 locations across Belgium, Taiwan, Germany, South Korea, Singapore, United States

Drugs / interventions tested

Conditions studied

Sponsor

Novartis Pharmaceuticals — full company profile →

Who can join

18 and older, any sex, with HCMV. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants Who Require Preemptive HCMV Therapy Primary · 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

GroupValue95% CI
Total CSJ148 (Cohort 1 & Cohort 2)24
Cohort 2: CSJ14823
Cohort 2: Placebo9
Number of Participants With Adverse Events as a Measure of Safety and Tolerability Primary · 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.

At least one treatment-emergent AE
GroupValue95% CI
Total CSJ148 (Cohort 1 & Cohort 2)65
Cohort 2: Placebo21
At least one drug-related AE
GroupValue95% CI
Total CSJ148 (Cohort 1 & Cohort 2)0
Cohort 2: Placebo2
At least one SAE
GroupValue95% CI
Total CSJ148 (Cohort 1 & Cohort 2)46
Cohort 2: Placebo15
At least one drug-related SAE
GroupValue95% CI
Total CSJ148 (Cohort 1 & Cohort 2)0
Cohort 2: Placebo1
Deaths
GroupValue95% CI
Total CSJ148 (Cohort 1 & Cohort 2)12
Cohort 2: Placebo0
At least 1 treatment-emergent AE grade 3 or higher
GroupValue95% CI
Total CSJ148 (Cohort 1 & Cohort 2)58
Cohort 2: Placebo17
Total deaths:those reported after study completion
GroupValue95% CI
Total CSJ148 (Cohort 1 & Cohort 2)19
Cohort 2: Placebo3
Discontinued study treatment due to any AE
GroupValue95% CI
Total CSJ148 (Cohort 1 & Cohort 2)1
Cohort 2: Placebo1
Time to Start of Preemptive HCMV Therapy Cohort 2 Secondary · 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

GroupValue95% CI
Cohort 2: CSJ14862.03± 12.145
Cohort 2: Placebo49.54± 13.470
Number of Times That Preemptive HCMV Therapy is Required -Cohort 2 Secondary · 98 days

Among those who required preemptive therapy, the number of times preemptive therapy was required. (Cohort 2)

GroupValue95% CI
Cohort 2: CSJ1482.0701.369 – 3.130
Cohort 2: Placebo2.5401.342 – 4.806
Proportion of Participants Developing HCMV Disease Secondary · 98 days

Proportion of participants developing HCMV disease

GroupValue95% CI
Cohort 2: CSJ1480.1190.048 – 0.234
Cohort 2: Placebo00 – 0.162
Area Under the Serum Concentration-time Curve During the Dosing Interval (AUCtau) for CSJ148 Only Secondary · 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

Day 1
GroupValue95% CI
Total CSJ148 (Cohort 1 & Cohort 2)7310± 2310
Day 29
GroupValue95% CI
Total CSJ148 (Cohort 1 & Cohort 2)9890± 3470
Day 57
GroupValue95% CI
Total CSJ148 (Cohort 1 & Cohort 2)11400± 4020
Day 85
GroupValue95% CI
Total CSJ148 (Cohort 1 & Cohort 2)12900± 4380
Maximum Serum Concentration During the Dosing Interval (Cmax) for CSJ148 Only Secondary · 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

Day 1
GroupValue95% CI
Total CSJ148 (Cohort 1 & Cohort 2)1040± 356
Day 29
GroupValue95% CI
Total CSJ148 (Cohort 1 & Cohort 2)1100± 282
Day 57
GroupValue95% CI
Total CSJ148 (Cohort 1 & Cohort 2)1180± 316
Day 85
GroupValue95% CI
Total CSJ148 (Cohort 1 & Cohort 2)1230± 458
Trough Serum Concentration (Ctrough) for CSJ148 Only Secondary · 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 \[ug / mL\]

Day 1
GroupValue95% CI
Total CSJ148 (Cohort 1 & Cohort 2)104± 59.7
Day 29
GroupValue95% CI
Total CSJ148 (Cohort 1 & Cohort 2)167± 85.5
Day 57
GroupValue95% CI
Total CSJ148 (Cohort 1 & Cohort 2)214± 152
Day 85
GroupValue95% CI
Total CSJ148 (Cohort 1 & Cohort 2)223± 104
Accumulation Ratio(Racc) for CSJ148 Only at Day 85 Secondary · 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).

GroupValue95% CI
Total CSJ148 (Cohort 1 & Cohort 2)1.83± 0.531
Lambda_z for CSJ148 Only at Day 85 Secondary · Day 85

Lambda\_z is the terminal elimination rate constant \[1/day\] at Day 85

GroupValue95% CI
Total CSJ148 (Cohort 1 & Cohort 2)0.0409± 0.0175
Half-life (T1/2) for CSJ148 Only at Day 85 Secondary · Day 85

T1/2 is the terminal elimination half-life \[time\]

GroupValue95% CI
Total CSJ148 (Cohort 1 & Cohort 2)19.7± 7.18

Adverse events — posted to ClinicalTrials.gov

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.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo
Serious: 15/21 (71%)
Deaths:
Total CSJ148
Serious: 46/65 (71%)
Deaths:

Serious adverse events (124 terms)

ReactionSystemPlaceboTotal CSJ148
Acute graft versus host diseaseImmune system disorders
Febrile neutropeniaBlood and lymphatic system disorders
PneumoniaInfections and infestations
SepsisInfections and infestations
Acute myeloid leukaemia recurrentNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute kidney injuryRenal and urinary disorders
Acute respiratory failureRespiratory, thoracic and mediastinal disorders
Non-cardiac chest painGeneral disorders
Septic shockInfections and infestations
Respiratory failureRespiratory, thoracic and mediastinal disorders
Atrial flutterCardiac disorders
Abdominal pain upperGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
Gastrointestinal haemorrhageGastrointestinal disorders
NauseaGastrointestinal disorders
VomitingGastrointestinal disorders
PyrexiaGeneral disorders
Cytomegalovirus colitisInfections and infestations
Cytomegalovirus infectionInfections and infestations
Cytomegalovirus viraemiaInfections and infestations
Epstein-Barr virus infectionInfections and infestations
Herpes zosterInfections and infestations
Staphylococcal sepsisInfections and infestations
Urinary tract infectionInfections and infestations
Alanine aminotransferase increasedInvestigations
Other adverse events (119 terms — click to expand)

ReactionSystemPlaceboTotal CSJ148
NauseaGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
VomitingGastrointestinal disorders
PyrexiaGeneral disorders
StomatitisGastrointestinal disorders
Decreased appetiteMetabolism and nutrition disorders
Febrile neutropeniaBlood and lymphatic system disorders
CoughRespiratory, thoracic and mediastinal disorders
HeadacheNervous system disorders
RashSkin and subcutaneous tissue disorders
HypertensionVascular disorders
HypokalaemiaMetabolism and nutrition disorders
ConstipationGastrointestinal disorders
FatigueGeneral disorders
PruritusSkin and subcutaneous tissue disorders
Back painMusculoskeletal and connective tissue disorders
Abdominal painGastrointestinal disorders
DizzinessNervous system disorders
ChillsGeneral disorders
InsomniaPsychiatric disorders
Dry eyeEye disorders
Acute graft versus host disease in skinImmune system disorders
HaemorrhoidsGastrointestinal disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
Oedema peripheralGeneral disorders
ArthralgiaMusculoskeletal and connective tissue disorders
Oropharyngeal painRespiratory, thoracic and mediastinal disorders
Dry mouthGastrointestinal disorders
Acute graft versus host diseaseImmune system disorders
HaematuriaRenal and urinary disorders
ThrombocytopeniaBlood and lymphatic system disorders
OesophagitisGastrointestinal disorders
HypomagnesaemiaMetabolism and nutrition disorders
Bone painMusculoskeletal and connective tissue disorders
Pleural effusionRespiratory, thoracic and mediastinal disorders
HypotensionVascular disorders
TachycardiaCardiac disorders
Gastrointestinal inflammationGastrointestinal disorders
Non-cardiac chest painGeneral disorders
Upper respiratory tract infectionInfections and infestations

Most-reported serious reactions: Acute graft versus host disease, Febrile neutropenia, Pneumonia, Sepsis, Acute myeloid leukaemia recurrent, Acute kidney injury, Acute respiratory failure, Non-cardiac chest pain.

Data from ClinicalTrials.gov NCT02268526 adverse events section.

Sponsor's own description

This study is designed to test if CSJ148 can prevent HCMV replication after stem cell transplantation.

Publications & conference data

7 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Antibody therapies for the prevention and treatment of viral infections.
    Salazar G, Zhang N, Fu TM, An Z. · · 2017 · cited 135× · PMID 29263875 · DOI 10.1038/s41541-017-0019-3
  2. How I treat resistant cytomegalovirus infection in hematopoietic cell transplantation recipients.
    El Chaer F, Shah DP, Chemaly RF. · · 2016 · cited 127× · PMID 27760756 · DOI 10.1182/blood-2016-06-688432
  3. Progress and Challenges in the Prevention, Diagnosis, and Management of Cytomegalovirus Infection in Transplantation.
    Limaye AP, Babu TM, Boeckh M. · · 2020 · cited 87× · PMID 33115722 · DOI 10.1128/cmr.00043-19
  4. Phase 2 Study of Anti-Human Cytomegalovirus Monoclonal Antibodies for Prophylaxis in Hematopoietic Cell Transplantation.
    Maertens J, Logan AC, Jang J, Long G, et al · · 2020 · cited 28× · PMID 32015031 · DOI 10.1128/aac.02467-19
  5. Human cytomegalovirus: pathogenesis, prevention, and treatment.
    Shang Z, Li X. · · 2024 · cited 19× · PMID 39585514 · DOI 10.1186/s43556-024-00226-7
  6. Immune Prophylaxis and Therapy for Human Cytomegalovirus Infection.
    Struble EB, Murata H, Komatsu T, Scott D. · · 2021 · cited 14× · PMID 34445434 · DOI 10.3390/ijms22168728
  7. Novel approaches to CMV after HCT: report from the 27th European Congress of Clinical Microbiology and Infectious Diseases, Vienna, Austria, 22-25 April 2017.
    Duarte RF, Lyon S. · · 2018 · cited 1× · PMID 29796299 · DOI 10.4155/fsoa-2018-0013

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing