A Study of MCMV5322A/MCMV3068A for the Prevention of Cytomegalovirus Disease in High-Risk Kidney Allograft Recipients

NCT01753167 | Completed Phase 2

• 2 other identifiers: GV284182012-002245-37
• Study Type: interventional
• Target: 122
• Locations: 8 countries
• Sites: 39

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).

Conditions

Cytomegalovirus Infections

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants With Adverse Events

  Baseline up to Week 24

• 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

  Baseline up to Week 12

Secondary Outcomes (12)

• Percentage of Participants With CMV Viral Load >= 150 Copies/mL During the First 24 Weeks After Transplantation

  Baseline up to Week 24

• Time to Detectable CMV Viral Load >=150 Copies/mL

  Baseline up to Week 24

• Viral Load at the First Detection of CMV DNAemia (>=150 Copies/mL), DNAemia is detection of deoxyribonucleic acid (DNA)

  Baseline up to Week 24

• Peak Viral Load on or Following First Detection of CMV DNAemia (>=150 Copies/mL)

  Baseline up to Week 24

• Percentage of Participants who Require Initiation of Pre-emptive Antiviral Therapy During the First 12 Weeks and 24 Weeks After Transplantation

  Baseline up to Weeks 12 and 24

Study Arms (2)

MCMV5322A/MCMV3068A

EXPERIMENTAL

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).

Drug: MCMV3068A; Drug: MCMV5322A

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

MCMV3068A DRUG

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.

MCMV5322A/MCMV3068A

MCMV5322A DRUG

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.

MCMV5322A/MCMV3068A

Placebo DRUG

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.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (39)

UCLA; Kidney & Pancreas Transplantation

Los Angeles, California, 90095, United States

Location

California Inst. of Renal Research

San Diego, California, 92123, United States

Location

Univ of CA San Francisco; Kidney Transplant Service

San Francisco, California, 94143-0780, United States

Location

University of Colorado Health Sciences Center; Dept of Medicine

Denver, Colorado, 80262, United States

Location

Georgetown Uni Hospital; Division of Transplant Surgery

Washington D.C., District of Columbia, 20007, United States

Location

MedStar Washington Hosp Center

Washington D.C., District of Columbia, 20010, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Georgia Regents University

Augusta, Georgia, 30912, United States

Location

Henry Ford Health System; Gastroenterology

Detroit, Michigan, 48202-2689, United States

Location

Washington Uni School of Medicine/Barnes Jewish Hospital; Renal

St Louis, Missouri, 63110, United States

Location

Erie County Medical Center; Dept. of Nephrology

Buffalo, New York, 14215, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Columbia University

New York, New York, 10032, United States

Location

University of Cincinnati / University of Cincinnati College of Medicine

Cincinnati, Ohio, 45267, United States

Location

Baylor Univ Medical Center

Dallas, Texas, 75246, United States

Location

Clin Univ de Bxl Hôpital Erasme

Brussels, 1070, Belgium

Location

UZ Gent

Ghent, 9000, Belgium

Location

UZ Leuven Gasthuisberg

Leuven, 3000, Belgium

Location

Hopital Pellegrin-CHU de Bordeaux; Service de Neurologie

Bordeaux, 33076, France

Location

CHU de Nantes; Institut de transplantation urologie-néphrologie

Nantes, 44093, France

Location

Hopital Necker

Paris, 75743, France

Location

Hopital Rangueil; Gastro Enterologie Et Nutrition

Toulouse, 31059, France

Location

Chu De Tours

Tours, 37000, France

Location

Hopitaux De Brabois; Nephrologie

Vandœuvre-lès-Nancy, 54511, France

Location

Universitätsklinikum "Carl Gustav Carus"; Medizinische Klinik III

Dresden, 01307, Germany

Location

Universitätsklinikum Essen Zentrum f.Innere Medizin Abt.Nephrologie

Essen, 45122, Germany

Location

Klinik Johann Wolfgang von Goethe Uni; Zentrum der Inneren Medizin; Medizinische Klinik III

Frankfurt, 60596, Germany

Location

Uniklinikum Heidelberg

Heidelberg, 69120, Germany

Location

Oslo Universitetssykehus HF, Rikshospitalet

Oslo, 0372, Norway

Location

Fundació Puigvert

Barcelona, Barcelona, 08025, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, Barcelona, 08035, Spain

Location

Hospital Clinic i Provincial de Barcelona

Barcelona, Barcelona, 08036, Spain

Location

Hospital Universitario de Bellvitge

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

Location

CEIC del Hospital Virgen del Rocío

Seville, Sevilla, 41013, Spain

Location

Sahlgrenska Universitetssjukhuset; Jubileumskliniken

Gothenburg, 413 45, Sweden

Location

Karolinska University Hospital

Huddinge, 141 86, Sweden

Location

Akademiska Sjukhuset; Transplantation Surgery

Uppsala, 751 85, Sweden

Location

Royal Free Hospital

London, NW3 2QS, United Kingdom

Location

Guys and St Thomas NHS Foundation Trust, Guys Hospital

London, SE1 9RT, United Kingdom

Location

Related Publications (4)

• Vernooij RW, Michael M, Colombijn JM, Owers DS, Webster AC, Strippoli GF, Hodson EM. Pre-emptive treatment for cytomegalovirus viraemia to prevent cytomegalovirus disease in solid organ transplant recipients. Cochrane Database Syst Rev. 2025 Jan 14;1(1):CD005133. doi: 10.1002/14651858.CD005133.pub4.

  PMID: 39807668 DERIVED

• Vernooij RW, Michael M, Ladhani M, Webster AC, Strippoli GF, Craig JC, Hodson EM. Antiviral medications for preventing cytomegalovirus disease in solid organ transplant recipients. Cochrane Database Syst Rev. 2024 May 3;5(5):CD003774. doi: 10.1002/14651858.CD003774.pub5.

  PMID: 38700045 DERIVED

• 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.

  PMID: 29133549 DERIVED

• 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.

  PMID: 27872061 DERIVED

MeSH Terms

Conditions

Cytomegalovirus Infections

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections

Study Officials

• Clinical Trials

  Genentech, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 17, 2012
• First Posted: December 20, 2012
• Study Start: December 14, 2012
• Primary Completion: October 15, 2014
• Study Completion: October 15, 2014
• Last Updated: March 8, 2017

Record last verified: 2017-03

Locations

NO (1); GB (2); DE (4); ES (5); SE (3); FR (6); US (15); BE (3)