Clinical trial NCT01753167: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cytomegalovirus Infections
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2012-12-20
Enrollment: 122
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


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

Primary outcomes:
measure: Percentage of Participants With Adverse Events
timeFrame: Baseline up to Week 24
measure: 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
timeFrame: Baseline up to Week 12
Secondary outcomes:
measure: Percentage of Participants With CMV Viral Load >= 150 Copies/mL During the First 24 Weeks After Transplantation
timeFrame: Baseline up to Week 24
measure: Time to Detectable CMV Viral Load >=150 Copies/mL
timeFrame: Baseline up to Week 24
measure: Viral Load at the First Detection of CMV DNAemia (>=150 Copies/mL), DNAemia is detection of deoxyribonucleic acid (DNA)
timeFrame: Baseline up to Week 24
measure: Peak Viral Load on or Following First Detection of CMV DNAemia (>=150 Copies/mL)
timeFrame: Baseline up to Week 24
measure: Percentage of Participants who Require Initiation of Pre-emptive Antiviral Therapy During the First 12 Weeks and 24 Weeks After Transplantation
timeFrame: Baseline up to Weeks 12 and 24
measure: Time to Initiation of First use of Preemptive Antiviral Therapy
timeFrame: Baseline up to Week 24
measure: Duration of First use of Preemptive Antiviral Therapy Initiated During the First 12 and 24 Weeks After Transplantation
timeFrame: Baseline up to Weeks 12 and 24
measure: Percentage of Participants With CMV Syndrome or Tissue-Invasive CMV Disease During the First 24 Weeks After Transplantation
timeFrame: Baseline up to Week 24
measure: Percentage of Participants With Change in CMV Serostatus
timeFrame: Baseline up to Week 24
measure: MCMV5322A Serum Concentrations
timeFrame: 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)
measure: MCMV3068A Serum Concentrations
timeFrame: 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)
measure: Percentage of Participants With Anti-therapeutic Antibodies (ATAs) to MCMV5322A and MCMV3068A
timeFrame: Predose (0 hours) on Days 1, 29, 57; at Days 85, 113, and 141; and at Study Completion (Day 169)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA; Kidney & Pancreas Transplantation
state: California
city: San Diego
country: United States
facility: California Inst. of Renal Research
state: California
city: San Francisco
country: United States
facility: Univ of CA San Francisco; Kidney Transplant Service
state: California
city: Denver
country: United States
facility: University of Colorado Health Sciences Center; Dept of Medicine
state: Colorado
city: Washington
country: United States
facility: Georgetown Uni Hospital; Division of Transplant Surgery
state: District of Columbia
city: Washington
country: United States
facility: MedStar Washington Hosp Center
state: District of Columbia
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Augusta
country: United States
facility: Georgia Regents University
state: Georgia
city: Detroit
country: United States
facility: Henry Ford Health System; Gastroenterology
state: Michigan
city: St Louis
country: United States
facility: Washington Uni School of Medicine/Barnes Jewish Hospital; Renal
state: Missouri
city: Buffalo
country: United States
facility: Erie County Medical Center; Dept. of Nephrology
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati / University of Cincinnati College of Medicine
state: Ohio
city: Dallas
country: United States
facility: Baylor Univ Medical Center
state: Texas
city: Bruxelles
country: Belgium
facility: Clin Univ de Bxl Hôpital Erasme
city: Gent
country: Belgium
facility: UZ Gent
city: Leuven
country: Belgium
facility: UZ Leuven Gasthuisberg
city: Bordeaux
country: France
facility: Hopital Pellegrin-CHU de Bordeaux; Service de Neurologie
city: Nantes
country: France
facility: CHU de Nantes; Institut de transplantation urologie-néphrologie
city: Paris
country: France
facility: Hopital Necker
city: Toulouse
country: France
facility: Hopital Rangueil; Gastro Enterologie Et Nutrition
city: Tours
country: France
facility: Chu De Tours
city: Vandoeuvre-les-nancy
country: France
facility: Hopitaux De Brabois; Nephrologie
city: Dresden
country: Germany
facility: Universitätsklinikum "Carl Gustav Carus"; Medizinische Klinik III
city: Essen
country: Germany
facility: Universitätsklinikum Essen Zentrum f.Innere Medizin Abt.Nephrologie
city: Frankfurt
country: Germany
facility: Klinik Johann Wolfgang von Goethe Uni; Zentrum der Inneren Medizin; Medizinische Klinik III
city: Heidelberg
country: Germany
facility: Uniklinikum Heidelberg
city: Oslo
country: Norway
facility: Oslo Universitetssykehus HF, Rikshospitalet
city: Hospitalet de Llobregat
country: Spain
facility: Hospital Universitario de Bellvitge
state: Barcelona
city: Barcelona
country: Spain
facility: Fundació Puigvert
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial de Barcelona
city: Sevilla
country: Spain
facility: CEIC del Hospital Virgen del Rocío
city: Göteborg
country: Sweden
facility: Sahlgrenska Universitetssjukhuset; Jubileumskliniken
city: Huddinge
country: Sweden
facility: Karolinska University Hospital
city: Uppsala
country: Sweden
facility: Akademiska Sjukhuset; Transplantation Surgery
city: London
country: United Kingdom
facility: Royal Free Hospital
city: London
country: United Kingdom
facility: Guys and St Thomas NHS Foundation Trust, Guys Hospital
Study officials:
affiliation: Genentech, Inc.
name: Clinical Trials
role: STUDY_DIRECTOR
References:
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.
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.