HCMVPhase 2NCT02268526
Efficacy and Safety Study of CSJ148 in Stem Cell Transplant Patients
A Phase 2 study testing CSJ148 in people with HCMV, run by Novartis Pharmaceuticals at 17 sites in 6 countries.
Trial summary
This study is designed to test if CSJ148 can prevent HCMV replication after stem cell transplantation. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HCMV
- What is being tested?
- CSJ148
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 86 participants
- Where
- 17 sitesin 6 countries
- Study dates
- 2 Jun 2015to 7 Dec 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 26Show fewer
- 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.
Trial locations and contacts
17 sites in 6 countries.
17 sites in 6 countries
United States5 sites
Novartis Investigative Site
Beech Grove, Indiana, 46107
Novartis Investigative Site
Durham, North Carolina, 27710
Novartis Investigative Site
Gainesville, Florida, 32610
Novartis Investigative Site
Houston, Texas, 77030
Novartis Investigative Site
San Francisco, California, 94143
Germany4 sites
Novartis Investigative Site
Erlangen, 91054
Novartis Investigative Site
Essen, 45147
Novartis Investigative Site
Regensburg, 93053
Novartis Investigative Site
Würzburg, 97070
Taiwan3 sites
Novartis Investigative Site
New Taipei City, 33305
Novartis Investigative Site
Taichung, 40447
Novartis Investigative Site
Taipei, 10002
Singapore2 sites
Novartis Investigative Site
Singapore, 119228
Novartis Investigative Site
Singapore, 169608
South Korea2 sites
Novartis Investigative Site
Seoul, Korea, 06351
Novartis Investigative Site
Seoul, 06591
About this study
Official title: A Multi-center, Randomized, Double-blind, Placebo Controlled, Study to Evaluate the Efficacy and Safety of CSJ148 Compared to Placebo to Prevent Human Cytomegalovirus (HCMV) Replication in Stem Cell Transplant Patients
This study is designed to test if CSJ148 can prevent HCMV replication after stem cell transplantation.
Read the 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.
- Conditions
- HCMV
- Being tested
- CSJ148, Placebo
- Keywords
- Safety, efficacy, pharmacokinetics, CSJ148, HCMV, HCMV viral load,, immunogenicity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CSJ148Biological
CSJ148 IV q 4weeks
PlaceboDrug
Placebo IV q 4weeks
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1: CSJ148 | Experimental | Cohort 1: CSJ148 IV q 4weeks Receives: Biological: CSJ148 |
| Cohort 2: CSJ148 | Experimental | Cohort 2: CSJ148 IV q 4weeks Receives: Biological: CSJ148 |
| Cohort 2: Placebo | Placebo comparator | Cohort 2: Placebo IV q 4weeks Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Who Require Preemptive HCMV Therapy
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
Measured: 98 days
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
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.
Measured: 98 days
Secondary outcomes (9)
Time to Start of Preemptive HCMV Therapy Cohort 2
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
Measured: 98 days
Number of Times That Preemptive HCMV Therapy is Required -Cohort 2
Among those who required preemptive therapy, the number of times preemptive therapy was required. (Cohort 2)
Measured: 98 days
Proportion of Participants Developing HCMV Disease
Proportion of participants developing HCMV disease
Measured: 98 days
Area Under the Serum Concentration-time Curve During the Dosing Interval (AUCtau) for CSJ148 Only
PK parameters were calculated from plasma concentration-time data using non-compartmental methods. The AUCtau was calculated using a linear trapezoidal method
Measured: Day 1, Day 29, Day 57, Day 85 at predose (0hr) and 3,6,24 hrs post dose
Maximum Serum Concentration During the Dosing Interval (Cmax) for CSJ148 Only
Cmax is the observed maximum plasma (or serum or blood) concentration following drug administration [ug / mL] for CSJ148 only
Measured: Day 1, Day 29, Day 57, Day 85 at predose (0hr) and 3,6,24 hrs post dose
Trough Serum Concentration (Ctrough) for CSJ148 Only
Ctrough is The observed plasma (or serum or blood) concentration at the end of a drug administration dosing interval [ug / mL]
Measured: Day 1, Day 29, Day 57, Day 85 at predose (0hr) and 3,6,24 hrs post dose
Accumulation Ratio(Racc) for CSJ148 Only at Day 85
Accumulation ratio(Racc) is Racc: Accumulation ratio, calculated by AUCtau (Day 85) divided by AUCtau (for the 1st dose at Day 1).
Measured: Day 1 and Day 85
Lambda_z for CSJ148 Only at Day 85
Lambda_z is the terminal elimination rate constant [1/day] at Day 85
Measured: Day 85
Half-life (T1/2) for CSJ148 Only at Day 85
T1/2 is the terminal elimination half-life [time]
Measured: Day 85
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Oct 2014 (estimated)
- Study start2 Jun 2015
- Primary completion7 Dec 2016
- Study completion7 Dec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HCMVStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 86 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02268526
- Sponsor's protocol ID
- CCSJ148X2201
- Status last verified
- Mar 2019
- First submitted
- 8 Aug 2014
- Last updated
- 5 Jan 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Publications
Maertens J, Logan AC, Jang J, Long G, Tang JL, Hwang WYK, Koh LP, Chemaly R, Gerbitz A, Winkler J, Yeh SP, Hiemenz J, Christoph S, Lee DG, Wang PN, Holler E, Mielke S, Akard L, Yeo A, Ramachandra S, Smith K, Pertel P, Segal F. Phase 2 Study of Anti-Human Cytomegalovirus Monoclonal Antibodies for Prophylaxis in Hematopoietic Cell Transplantation. Antimicrob Agents Chemother. 2020 Mar 24;64(4):e02467-19. doi: 10.1128/AAC.02467-19. Print 2020 Mar 24.
PubMed 32015031
Study at a glance
From the registry record, last updated by the sponsor on 5 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-center, Randomized, Double-blind, Placebo Controlled, Study to Evaluate the Efficacy and Safety of CSJ148 Compared to Placebo to Prevent Human Cytomegalovirus (HCMV) Replication in Stem Cell Transplant Patients
- ClinicalTrials.gov ID
- NCT02268526
- Acronym / sponsor ID
- CCSJ148X2201
- Conditions
- HCMV
- Keywords
- Safety, efficacy, pharmacokinetics, CSJ148, HCMV, HCMV viral load,, immunogenicity
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 86 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 2 Jun 2015 (actual)
- Primary completion
- 7 Dec 2016 (actual)
- Study completion
- 7 Dec 2016 (actual)
- First posted
- 20 Oct 2014 (estimated)
- Results
- Posted 26 Feb 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is designed to test if CSJ148 can prevent HCMV replication after stem cell transplantation.
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
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cohort 1: CSJ148 | Experimental | Biological: CSJ148Cohort 1: CSJ148 IV q 4weeks |
| Cohort 2: CSJ148 | Experimental | Biological: CSJ148Cohort 2: CSJ148 IV q 4weeks |
| Cohort 2: Placebo | Placebo comparator | Drug: PlaceboCohort 2: Placebo IV q 4weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (26 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CSJ148CSJ148 IV q 4weeks | Biological | Cohort 1: CSJ148, Cohort 2: CSJ148 |
| PlaceboPlacebo IV q 4weeks | Drug | Cohort 2: Placebo |
Primary outcome
Number of Participants Who Require Preemptive HCMV Therapy
Time frame: 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
Time frame: 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.
9 secondary outcomes
Time to Start of Preemptive HCMV Therapy Cohort 2
Time frame: 98 days
Number of Times That Preemptive HCMV Therapy is Required -Cohort 2
Time frame: 98 days
Proportion of Participants Developing HCMV Disease
Time frame: 98 days
Area Under the Serum Concentration-time Curve During the Dosing Interval (AUCtau) for CSJ148 Only
Time frame: Day 1, Day 29, Day 57, Day 85 at predose (0hr) and 3,6,24 hrs post dose
Maximum Serum Concentration During the Dosing Interval (Cmax) for CSJ148 Only
Time frame: Day 1, Day 29, Day 57, Day 85 at predose (0hr) and 3,6,24 hrs post dose
Trough Serum Concentration (Ctrough) for CSJ148 Only
Time frame: Day 1, Day 29, Day 57, Day 85 at predose (0hr) and 3,6,24 hrs post dose
Accumulation Ratio(Racc) for CSJ148 Only at Day 85
Time frame: Day 1 and Day 85
Lambda_z for CSJ148 Only at Day 85
Time frame: Day 85
Half-life (T1/2) for CSJ148 Only at Day 85
Time frame: Day 85
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jan 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32015031Maertens J, Logan AC, Jang J, Long G, Tang JL, Hwang WYK, Koh LP, Chemaly R, Gerbitz A, Winkler J, Yeh SP, Hiemenz J, Christoph S, Lee DG, Wang PN, Holler E, Mielke S, Akard L, Yeo A, Ramachandra S, Smith K, Pertel P, Segal F. Phase 2 Study of Anti-Human Cytomegalovirus Monoclonal Antibodies for Prophylaxis in Hematopoietic Cell Transplantation. Antimicrob Agents Chemother. 2020 Mar 24;64(4):e02467-19. doi: 10.1128/AAC.02467-19. Print 2020 Mar 24.
- A Plain Language Trial Summary is available on novartisclinicaltrials.comLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
17 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing CSJ148 in people with HCMV, run by Novartis Pharmaceuticals at 17 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in United States, Germany, Taiwan, Singapore, South Korea and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Feb 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants Who Require Preemptive HCMV Therapy (time frame: 98 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02268526, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jan 2021.