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

Cytomegalovirus Infections Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01753167
• Other study ID #: GV28418
• Secondary ID: 2012-002245-37
• Status: Completed
• Phase: Phase 2
• First received: December 17, 2012
• Last updated: March 7, 2017
• Start date: December 14, 2012
• Est. completion date: October 15, 2014

Study information

• Verified date: March 2017
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 122
• Est. completion date: October 15, 2014
• Est. primary completion date: October 15, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cytomegalovirus Infections

Intervention

Drug:
• MCMV3068A
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
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.
• Placebo
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.

Locations

Country	Name	City	State
Belgium	Clin Univ de Bxl Hôpital Erasme	Bruxelles
Belgium	UZ Gent	Gent
Belgium	UZ Leuven Gasthuisberg	Leuven
France	Hopital Pellegrin-CHU de Bordeaux; Service de Neurologie	Bordeaux
France	CHU de Nantes; Institut de transplantation urologie-néphrologie	Nantes
France	Hopital Necker	Paris
France	Hopital Rangueil; Gastro Enterologie Et Nutrition	Toulouse
France	Chu De Tours	Tours
France	Hopitaux De Brabois; Nephrologie	Vandoeuvre-les-nancy
Germany	Universitätsklinikum "Carl Gustav Carus"; Medizinische Klinik III	Dresden
Germany	Universitätsklinikum Essen Zentrum f.Innere Medizin Abt.Nephrologie	Essen
Germany	Klinik Johann Wolfgang von Goethe Uni; Zentrum der Inneren Medizin; Medizinische Klinik III	Frankfurt
Germany	Uniklinikum Heidelberg	Heidelberg
Norway	Oslo Universitetssykehus HF, Rikshospitalet	Oslo
Spain	Fundació Puigvert	Barcelona
Spain	Hospital Clinic i Provincial de Barcelona	Barcelona
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital Universitario de Bellvitge	Hospitalet de Llobregat	Barcelona
Spain	CEIC del Hospital Virgen del Rocío	Sevilla
Sweden	Sahlgrenska Universitetssjukhuset; Jubileumskliniken	Göteborg
Sweden	Karolinska University Hospital	Huddinge
Sweden	Akademiska Sjukhuset; Transplantation Surgery	Uppsala
United Kingdom	Guys and St Thomas NHS Foundation Trust, Guys Hospital	London
United Kingdom	Royal Free Hospital	London
United States	Emory University	Atlanta	Georgia
United States	Georgia Regents University	Augusta	Georgia
United States	Erie County Medical Center; Dept. of Nephrology	Buffalo	New York
United States	University of Cincinnati / University of Cincinnati College of Medicine	Cincinnati	Ohio
United States	Baylor Univ Medical Center	Dallas	Texas
United States	University of Colorado Health Sciences Center; Dept of Medicine	Denver	Colorado
United States	Henry Ford Health System; Gastroenterology	Detroit	Michigan
United States	UCLA; Kidney & Pancreas Transplantation	Los Angeles	California
United States	Columbia University	New York	New York
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	California Inst. of Renal Research	San Diego	California
United States	Univ of CA San Francisco; Kidney Transplant Service	San Francisco	California
United States	Washington Uni School of Medicine/Barnes Jewish Hospital; Renal	St Louis	Missouri
United States	Georgetown Uni Hospital; Division of Transplant Surgery	Washington	District of Columbia
United States	MedStar Washington Hosp Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Countries where clinical trial is conducted

United States,  Belgium,  France,  Germany,  Norway,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Adverse Events		Baseline up to Week 24
Primary	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	Percentage of Participants With CMV Viral Load >= 150 Copies/mL During the First 24 Weeks After Transplantation		Baseline up to Week 24
Secondary	Time to Detectable CMV Viral Load >=150 Copies/mL		Baseline up to Week 24
Secondary	Viral Load at the First Detection of CMV DNAemia (>=150 Copies/mL), DNAemia is detection of deoxyribonucleic acid (DNA)		Baseline up to Week 24
Secondary	Peak Viral Load on or Following First Detection of CMV DNAemia (>=150 Copies/mL)		Baseline up to Week 24
Secondary	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
Secondary	Time to Initiation of First use of Preemptive Antiviral Therapy		Baseline up to Week 24
Secondary	Duration of First use of Preemptive Antiviral Therapy Initiated During the First 12 and 24 Weeks After Transplantation		Baseline up to Weeks 12 and 24
Secondary	Percentage of Participants With CMV Syndrome or Tissue-Invasive CMV Disease During the First 24 Weeks After Transplantation		Baseline up to Week 24
Secondary	Percentage of Participants With Change in CMV Serostatus		Baseline up to Week 24
Secondary	MCMV5322A Serum Concentrations		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)
Secondary	MCMV3068A Serum Concentrations		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)
Secondary	Percentage of Participants With Anti-therapeutic Antibodies (ATAs) to MCMV5322A and MCMV3068A		Predose (0 hours) on Days 1, 29, 57; at Days 85, 113, and 141; and at Study Completion (Day 169)