Back to resultsA Study of MCMV5322A/MCMV3068A for the Prevention of Cytomegalovirus Disease in High-Risk Kidney Allograft Recipients
Primary Purpose
Cytomegalovirus Infections
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
MCMV3068A
MCMV5322A
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Cytomegalovirus Infections
Eligibility Criteria
Inclusion Criteria:
- Participant is scheduled to receive a primary or secondary renal allograft from a donor
- Participant is seronegative for CMV and is receiving an allograft from a CMV-seropositive donor
- Female participants of child-bearing age must have a negative pregnancy test result on Day 1, prior to infusion
- For women who are not postmenopausal or surgically sterile (defined as absence of ovaries and/or uterus): agreement to remain completely abstinent or use two methods of contraception at all times
Exclusion Criteria:
- Participant is suspected of having CMV disease
- Participant has received anti-CMV therapy within the 30 days prior to screening (exceptions are the use of acyclovir, valacyclovir, or famciclovir for up to 10 days duration for treatment of acute herpes simplex or herpes zoster or participants receiving acyclovir or valacyclovir at doses to suppress herpes zoster)
- Participants who have received intravenous immunoglobulin (IVIG) within 3 months before transplantation or with expectation of receiving IVIG at time of transplantation or in the 3 months after transplantation
- Participants who have received B cell-depleting therapies (including but not limited to rituximab) within 3 months before transplantation or with the expectation of receiving such therapy at the time of transplantation or in the 3 months after transplantation
- Participant is receiving a multi-organ transplant (e.g., liver or pancreas in addition to kidney)
- Active or chronic hepatic or hepatobiliary disease (including known Gilbert's syndrome) or elevations in a hepatic transaminase or bilirubin >= 2 times upper limits of normal (ULN)
- Participant is unlikely or unwilling to be available for follow-up for the full 24-week duration of the study
- Female participants who are pregnant, plan to become pregnant during the study, or who are breastfeeding
- History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins or human-derived immunoglobulin preparations; or any constituent of MCMV5322A/MCMV3068A or placebo
- Active treatment for untreated tuberculosis or other infectious conditions that are significant in the judgment of the investigator
- Infection with hepatitis B, hepatitis C or human immunodeficiency virus
- Previous exposure to any investigational agent within 12 weeks or 5 half-lives
- Any other acute or chronic condition, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that, in the opinion of the Principal Investigator, contraindicates the use of an investigational drug or that may affect the interpretation of the results or that renders the participant at high risk for treatment complications
- History of alcoholism or substance abuse within 6 months before screening
- Participant is expected to require treatment or prophylaxis with an antiviral with anti-CMV activity during the study
Sites / Locations
- UCLA; Kidney & Pancreas Transplantation
- California Inst. of Renal Research
- Univ of CA San Francisco; Kidney Transplant Service
- University of Colorado Health Sciences Center; Dept of Medicine
- Georgetown Uni Hospital; Division of Transplant Surgery
- MedStar Washington Hosp Center
- Emory University
- Georgia Regents University
- Henry Ford Health System; Gastroenterology
- Washington Uni School of Medicine/Barnes Jewish Hospital; Renal
- Erie County Medical Center; Dept. of Nephrology
- Icahn School of Medicine at Mount Sinai
- Columbia University
- University of Cincinnati / University of Cincinnati College of Medicine
- Baylor Univ Medical Center
- Clin Univ de Bxl Hôpital Erasme
- UZ Gent
- UZ Leuven Gasthuisberg
- Hopital Pellegrin-CHU de Bordeaux; Service de Neurologie
- CHU de Nantes; Institut de transplantation urologie-néphrologie
- Hopital Necker
- Hopital Rangueil; Gastro Enterologie Et Nutrition
- Chu De Tours
- Hopitaux De Brabois; Nephrologie
- Universitätsklinikum "Carl Gustav Carus"; Medizinische Klinik III
- Universitätsklinikum Essen Zentrum f.Innere Medizin Abt.Nephrologie
- Klinik Johann Wolfgang von Goethe Uni; Zentrum der Inneren Medizin; Medizinische Klinik III
- Uniklinikum Heidelberg
- Oslo Universitetssykehus HF, Rikshospitalet
- Hospital Universitario de Bellvitge
- Fundació Puigvert
- Hospital Universitari Vall d'Hebron
- Hospital Clinic i Provincial de Barcelona
- CEIC del Hospital Virgen del Rocío
- Sahlgrenska Universitetssjukhuset; Jubileumskliniken
- Karolinska University Hospital
- Akademiska Sjukhuset; Transplantation Surgery
- Royal Free Hospital
- Guys and St Thomas NHS Foundation Trust, Guys Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
MCMV5322A/MCMV3068A
Placebo
Arm Description
Participants will receive a total of four doses of study drug administered by intravenous infusion: at the time of transplantation (Day 1), and at Days 8, 29, and 57. MCMV5322A/MCMV3068A will be tested in this study at 10 milligrams per kilogram (mg/kg) of each component antibody. Thus, at each dose, 10 mg/kg of MCMV5322A and 10 mg/kg of MCMV3068A will be tested (20 mg/kg total).
Participants will receive a total of four doses of placebo matched with MCMV5322A/MCMV3068A administered by intravenous infusion: at the time of transplantation (Day 1), and at Days 8, 29, and 57.
Outcomes
Primary Outcome Measures
Percentage of Participants With Adverse Events
Percentage of Participants With CMV Viral Load Greater than or Equal to (>=) 150 Copies per Milliliter (Copies/mL) During the First 12 Weeks After Transplantation
Secondary Outcome Measures
Percentage of Participants With CMV Viral Load >= 150 Copies/mL During the First 24 Weeks After Transplantation
Time to Detectable CMV Viral Load >=150 Copies/mL
Viral Load at the First Detection of CMV DNAemia (>=150 Copies/mL), DNAemia is detection of deoxyribonucleic acid (DNA)
Peak Viral Load on or Following First Detection of CMV DNAemia (>=150 Copies/mL)
Percentage of Participants who Require Initiation of Pre-emptive Antiviral Therapy During the First 12 Weeks and 24 Weeks After Transplantation
Time to Initiation of First use of Preemptive Antiviral Therapy
Duration of First use of Preemptive Antiviral Therapy Initiated During the First 12 and 24 Weeks After Transplantation
Percentage of Participants With CMV Syndrome or Tissue-Invasive CMV Disease During the First 24 Weeks After Transplantation
Percentage of Participants With Change in CMV Serostatus
MCMV5322A Serum Concentrations
MCMV3068A Serum Concentrations
Percentage of Participants With Anti-therapeutic Antibodies (ATAs) to MCMV5322A and MCMV3068A
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01753167
Brief Title
A Study of MCMV5322A/MCMV3068A for the Prevention of Cytomegalovirus Disease in High-Risk Kidney Allograft Recipients
Official Title
A Phase II Randomized, Double-blind, Placebo-controlled Trial of MCMV5322A/MCMV3068A for the Prevention of Cytomegalovirus Disease in High-risk Kidney Allograft Recipients
Study Type
Interventional
2. Study Status
Record Verification Date
March 2017
Overall Recruitment Status
Completed
Study Start Date
December 14, 2012 (Actual)
Primary Completion Date
October 15, 2014 (Actual)
Study Completion Date
October 15, 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Genentech, Inc.
4. Oversight
5. Study Description
Brief Summary
This is a Phase II, randomized, double-blind, placebo-controlled study designed to assess the safety and clinical activity of multiple intravenous doses of MCMV5322A/MCMV3068A in cytomegalovirus (CMV)-seronegative recipients of a renal transplant from a CMV-seropositive donor, with use of a preemptive approach for prevention of CMV disease. Participants will be randomized into two treatment groups: active or placebo control; both arms will be followed preemptively. The study has a planned enrollment of approximately 120 participants (60 active and 60 placebo).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cytomegalovirus Infections
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Enrollment
122 (Actual)
8. Arms, Groups, and Interventions
Arm Title
MCMV5322A/MCMV3068A
Arm Type
Experimental
Arm Description
Participants will receive a total of four doses of study drug administered by intravenous infusion: at the time of transplantation (Day 1), and at Days 8, 29, and 57. MCMV5322A/MCMV3068A will be tested in this study at 10 milligrams per kilogram (mg/kg) of each component antibody. Thus, at each dose, 10 mg/kg of MCMV5322A and 10 mg/kg of MCMV3068A will be tested (20 mg/kg total).
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants will receive a total of four doses of placebo matched with MCMV5322A/MCMV3068A administered by intravenous infusion: at the time of transplantation (Day 1), and at Days 8, 29, and 57.
Intervention Type
Drug
Intervention Name(s)
MCMV3068A
Intervention Description
Four doses of MCMV3068A (10 mg/kg) administered by intravenous infusion at the time of transplantation (Day 1), and at Days 8, 29, and 57.
Intervention Type
Drug
Intervention Name(s)
MCMV5322A
Intervention Description
Four doses of MCMV5322A (10 mg/kg) administered by intravenous infusion at the time of transplantation (Day 1), and at Days 8, 29, and 57.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Four doses of placebo matched to MCMV5322A/MCMV3068A administered by intravenous infusion at the time of transplantation (Day 1), and at Days 8, 29, and 57.
Primary Outcome Measure Information:
Title
Percentage of Participants With Adverse Events
Time Frame
Baseline up to Week 24
Title
Percentage of Participants With CMV Viral Load Greater than or Equal to (>=) 150 Copies per Milliliter (Copies/mL) During the First 12 Weeks After Transplantation
Time Frame
Baseline up to Week 12
Secondary Outcome Measure Information:
Title
Percentage of Participants With CMV Viral Load >= 150 Copies/mL During the First 24 Weeks After Transplantation
Time Frame
Baseline up to Week 24
Title
Time to Detectable CMV Viral Load >=150 Copies/mL
Time Frame
Baseline up to Week 24
Title
Viral Load at the First Detection of CMV DNAemia (>=150 Copies/mL), DNAemia is detection of deoxyribonucleic acid (DNA)
Time Frame
Baseline up to Week 24
Title
Peak Viral Load on or Following First Detection of CMV DNAemia (>=150 Copies/mL)
Time Frame
Baseline up to Week 24
Title
Percentage of Participants who Require Initiation of Pre-emptive Antiviral Therapy During the First 12 Weeks and 24 Weeks After Transplantation
Time Frame
Baseline up to Weeks 12 and 24
Title
Time to Initiation of First use of Preemptive Antiviral Therapy
Time Frame
Baseline up to Week 24
Title
Duration of First use of Preemptive Antiviral Therapy Initiated During the First 12 and 24 Weeks After Transplantation
Time Frame
Baseline up to Weeks 12 and 24
Title
Percentage of Participants With CMV Syndrome or Tissue-Invasive CMV Disease During the First 24 Weeks After Transplantation
Time Frame
Baseline up to Week 24
Title
Percentage of Participants With Change in CMV Serostatus
Time Frame
Baseline up to Week 24
Title
MCMV5322A Serum Concentrations
Time Frame
Up to 24 hours prior to dosing (Day 1) and 1, 4, 24, and 72 hours postdose; predose (0 hours) and 1 hour postdose on Days 8, 29, 57; on Days 43, 58, 64, 71, 78, 85, 113, and 141; at study completion (Day 169)
Title
MCMV3068A Serum Concentrations
Time Frame
Up to 24 hours prior to dosing (Day 1) and 1, 4, 24, and 72 hours postdose; predose (0 hours) and 1 hour postdose on Days 8, 29, 57; on Days 43, 58, 64, 71, 78, 85, 113, and 141; at study completion (Day 169)
Title
Percentage of Participants With Anti-therapeutic Antibodies (ATAs) to MCMV5322A and MCMV3068A
Time Frame
Predose (0 hours) on Days 1, 29, 57; at Days 85, 113, and 141; and at Study Completion (Day 169)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Participant is scheduled to receive a primary or secondary renal allograft from a donor
Participant is seronegative for CMV and is receiving an allograft from a CMV-seropositive donor
Female participants of child-bearing age must have a negative pregnancy test result on Day 1, prior to infusion
For women who are not postmenopausal or surgically sterile (defined as absence of ovaries and/or uterus): agreement to remain completely abstinent or use two methods of contraception at all times
Exclusion Criteria:
Participant is suspected of having CMV disease
Participant has received anti-CMV therapy within the 30 days prior to screening (exceptions are the use of acyclovir, valacyclovir, or famciclovir for up to 10 days duration for treatment of acute herpes simplex or herpes zoster or participants receiving acyclovir or valacyclovir at doses to suppress herpes zoster)
Participants who have received intravenous immunoglobulin (IVIG) within 3 months before transplantation or with expectation of receiving IVIG at time of transplantation or in the 3 months after transplantation
Participants who have received B cell-depleting therapies (including but not limited to rituximab) within 3 months before transplantation or with the expectation of receiving such therapy at the time of transplantation or in the 3 months after transplantation
Participant is receiving a multi-organ transplant (e.g., liver or pancreas in addition to kidney)
Active or chronic hepatic or hepatobiliary disease (including known Gilbert's syndrome) or elevations in a hepatic transaminase or bilirubin >= 2 times upper limits of normal (ULN)
Participant is unlikely or unwilling to be available for follow-up for the full 24-week duration of the study
Female participants who are pregnant, plan to become pregnant during the study, or who are breastfeeding
History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins or human-derived immunoglobulin preparations; or any constituent of MCMV5322A/MCMV3068A or placebo
Active treatment for untreated tuberculosis or other infectious conditions that are significant in the judgment of the investigator
Infection with hepatitis B, hepatitis C or human immunodeficiency virus
Previous exposure to any investigational agent within 12 weeks or 5 half-lives
Any other acute or chronic condition, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that, in the opinion of the Principal Investigator, contraindicates the use of an investigational drug or that may affect the interpretation of the results or that renders the participant at high risk for treatment complications
History of alcoholism or substance abuse within 6 months before screening
Participant is expected to require treatment or prophylaxis with an antiviral with anti-CMV activity during the study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Genentech, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
UCLA; Kidney & Pancreas Transplantation
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
California Inst. of Renal Research
City
San Diego
State/Province
California
ZIP/Postal Code
92123
Country
United States
Facility Name
Univ of CA San Francisco; Kidney Transplant Service
City
San Francisco
State/Province
California
ZIP/Postal Code
94143-0780
Country
United States
Facility Name
University of Colorado Health Sciences Center; Dept of Medicine
City
Denver
State/Province
Colorado
ZIP/Postal Code
80262
Country
United States
Facility Name
Georgetown Uni Hospital; Division of Transplant Surgery
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
Facility Name
MedStar Washington Hosp Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Facility Name
Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Georgia Regents University
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30912
Country
United States
Facility Name
Henry Ford Health System; Gastroenterology
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202-2689
Country
United States
Facility Name
Washington Uni School of Medicine/Barnes Jewish Hospital; Renal
City
St Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Erie County Medical Center; Dept. of Nephrology
City
Buffalo
State/Province
New York
ZIP/Postal Code
14215
Country
United States
Facility Name
Icahn School of Medicine at Mount Sinai
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Columbia University
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
University of Cincinnati / University of Cincinnati College of Medicine
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267
Country
United States
Facility Name
Baylor Univ Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
Facility Name
Clin Univ de Bxl Hôpital Erasme
City
Bruxelles
ZIP/Postal Code
1070
Country
Belgium
Facility Name
UZ Gent
City
Gent
ZIP/Postal Code
9000
Country
Belgium
Facility Name
UZ Leuven Gasthuisberg
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Hopital Pellegrin-CHU de Bordeaux; Service de Neurologie
City
Bordeaux
ZIP/Postal Code
33076
Country
France
Facility Name
CHU de Nantes; Institut de transplantation urologie-néphrologie
City
Nantes
ZIP/Postal Code
44093
Country
France
Facility Name
Hopital Necker
City
Paris
ZIP/Postal Code
75743
Country
France
Facility Name
Hopital Rangueil; Gastro Enterologie Et Nutrition
City
Toulouse
ZIP/Postal Code
31059
Country
France
Facility Name
Chu De Tours
City
Tours
ZIP/Postal Code
37000
Country
France
Facility Name
Hopitaux De Brabois; Nephrologie
City
Vandoeuvre-les-nancy
ZIP/Postal Code
54511
Country
France
Facility Name
Universitätsklinikum "Carl Gustav Carus"; Medizinische Klinik III
City
Dresden
ZIP/Postal Code
01307
Country
Germany
Facility Name
Universitätsklinikum Essen Zentrum f.Innere Medizin Abt.Nephrologie
City
Essen
ZIP/Postal Code
45122
Country
Germany
Facility Name
Klinik Johann Wolfgang von Goethe Uni; Zentrum der Inneren Medizin; Medizinische Klinik III
City
Frankfurt
ZIP/Postal Code
60596
Country
Germany
Facility Name
Uniklinikum Heidelberg
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Facility Name
Oslo Universitetssykehus HF, Rikshospitalet
City
Oslo
ZIP/Postal Code
0372
Country
Norway
Facility Name
Hospital Universitario de Bellvitge
City
Hospitalet de Llobregat
State/Province
Barcelona
ZIP/Postal Code
08907
Country
Spain
Facility Name
Fundació Puigvert
City
Barcelona
ZIP/Postal Code
08025
Country
Spain
Facility Name
Hospital Universitari Vall d'Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital Clinic i Provincial de Barcelona
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Facility Name
CEIC del Hospital Virgen del Rocío
City
Sevilla
ZIP/Postal Code
41013
Country
Spain
Facility Name
Sahlgrenska Universitetssjukhuset; Jubileumskliniken
City
Göteborg
ZIP/Postal Code
413 45
Country
Sweden
Facility Name
Karolinska University Hospital
City
Huddinge
ZIP/Postal Code
141 86
Country
Sweden
Facility Name
Akademiska Sjukhuset; Transplantation Surgery
City
Uppsala
ZIP/Postal Code
751 85
Country
Sweden
Facility Name
Royal Free Hospital
City
London
ZIP/Postal Code
NW3 2QS
Country
United Kingdom
Facility Name
Guys and St Thomas NHS Foundation Trust, Guys Hospital
City
London
ZIP/Postal Code
SE1 9RT
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
29133549
Citation
Deng R, Wang Y, Maia M, Burgess T, McBride JM, Liao XC, Tavel JA, Hanley WD. Pharmacokinetics and Exposure-Response Analysis of RG7667, a Combination of Two Anticytomegalovirus Monoclonal Antibodies, in a Phase 2a Randomized Trial To Prevent Cytomegalovirus Infection in High-Risk Kidney Transplant Recipients. Antimicrob Agents Chemother. 2018 Jan 25;62(2):e01108-17. doi: 10.1128/AAC.01108-17. Print 2018 Feb.
Results Reference
derived
PubMed Identifier
27872061
Citation
Ishida JH, Patel A, Mehta AK, Gatault P, McBride JM, Burgess T, Derby MA, Snydman DR, Emu B, Feierbach B, Fouts AE, Maia M, Deng R, Rosenberger CM, Gennaro LA, Striano NS, Liao XC, Tavel JA. Phase 2 Randomized, Double-Blind, Placebo-Controlled Trial of RG7667, a Combination Monoclonal Antibody, for Prevention of Cytomegalovirus Infection in High-Risk Kidney Transplant Recipients. Antimicrob Agents Chemother. 2017 Jan 24;61(2):e01794-16. doi: 10.1128/AAC.01794-16. Print 2017 Feb.
Results Reference
derived
Learn more about this trial
A Study of MCMV5322A/MCMV3068A for the Prevention of Cytomegalovirus Disease in High-Risk Kidney Allograft Recipients
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