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

Sponsor

Genentech, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT01753167

Collaborator

(none)

122

Enrollment

Locations

Arms

Actual Duration (Months)

3.1

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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).

Condition or Disease	Intervention/Treatment	Phase
Cytomegalovirus Infections	Drug: MCMV3068A Drug: MCMV5322A Drug: Placebo	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

122 participants

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Dec 14, 2012

Actual Primary Completion Date :

Oct 15, 2014

Actual Study Completion Date :

Oct 15, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MCMV5322A/MCMV3068A 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 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. Drug: 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 Comparator: Placebo 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 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.

Arm

Intervention/Treatment

Experimental: MCMV5322A/MCMV3068A

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

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.

Drug: 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 Comparator: Placebo

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

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.

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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]
Time to Initiation of First use of Preemptive Antiviral Therapy [Baseline up to Week 24]
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]
Percentage of Participants With CMV Syndrome or Tissue-Invasive CMV Disease During the First 24 Weeks After Transplantation [Baseline up to Week 24]
Percentage of Participants With Change in CMV Serostatus [Baseline up to Week 24]
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)]
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)]
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)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCLA; Kidney & Pancreas Transplantation	Los Angeles	California	United States	90095
2	California Inst. of Renal Research	San Diego	California	United States	92123
3	Univ of CA San Francisco; Kidney Transplant Service	San Francisco	California	United States	94143-0780
4	University of Colorado Health Sciences Center; Dept of Medicine	Denver	Colorado	United States	80262
5	Georgetown Uni Hospital; Division of Transplant Surgery	Washington	District of Columbia	United States	20007
6	MedStar Washington Hosp Center	Washington	District of Columbia	United States	20010
7	Emory University	Atlanta	Georgia	United States	30322
8	Georgia Regents University	Augusta	Georgia	United States	30912
9	Henry Ford Health System; Gastroenterology	Detroit	Michigan	United States	48202-2689
10	Washington Uni School of Medicine/Barnes Jewish Hospital; Renal	St Louis	Missouri	United States	63110
11	Erie County Medical Center; Dept. of Nephrology	Buffalo	New York	United States	14215
12	Icahn School of Medicine at Mount Sinai	New York	New York	United States	10029
13	Columbia University	New York	New York	United States	10032
14	University of Cincinnati / University of Cincinnati College of Medicine	Cincinnati	Ohio	United States	45267
15	Baylor Univ Medical Center	Dallas	Texas	United States	75246
16	Clin Univ de Bxl Hôpital Erasme	Bruxelles		Belgium	1070
17	UZ Gent	Gent		Belgium	9000
18	UZ Leuven Gasthuisberg	Leuven		Belgium	3000
19	Hopital Pellegrin-CHU de Bordeaux; Service de Neurologie	Bordeaux		France	33076
20	CHU de Nantes; Institut de transplantation urologie-néphrologie	Nantes		France	44093
21	Hopital Necker	Paris		France	75743
22	Hopital Rangueil; Gastro Enterologie Et Nutrition	Toulouse		France	31059
23	Chu De Tours	Tours		France	37000
24	Hopitaux De Brabois; Nephrologie	Vandoeuvre-les-nancy		France	54511
25	Universitätsklinikum "Carl Gustav Carus"; Medizinische Klinik III	Dresden		Germany	01307
26	Universitätsklinikum Essen Zentrum f.Innere Medizin Abt.Nephrologie	Essen		Germany	45122
27	Klinik Johann Wolfgang von Goethe Uni; Zentrum der Inneren Medizin; Medizinische Klinik III	Frankfurt		Germany	60596
28	Uniklinikum Heidelberg	Heidelberg		Germany	69120
29	Oslo Universitetssykehus HF, Rikshospitalet	Oslo		Norway	0372
30	Hospital Universitario de Bellvitge	Hospitalet de Llobregat	Barcelona	Spain	08907
31	Fundació Puigvert	Barcelona		Spain	08025
32	Hospital Universitari Vall d'Hebron	Barcelona		Spain	08035
33	Hospital Clinic i Provincial de Barcelona	Barcelona		Spain	08036
34	CEIC del Hospital Virgen del Rocío	Sevilla		Spain	41013
35	Sahlgrenska Universitetssjukhuset; Jubileumskliniken	Göteborg		Sweden	413 45
36	Karolinska University Hospital	Huddinge		Sweden	141 86
37	Akademiska Sjukhuset; Transplantation Surgery	Uppsala		Sweden	751 85
38	Royal Free Hospital	London		United Kingdom	NW3 2QS
39	Guys and St Thomas NHS Foundation Trust, Guys Hospital	London		United Kingdom	SE1 9RT

Sponsors and Collaborators

Genentech, Inc.

Investigators

Study Director: Clinical Trials, Genentech, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Genentech, Inc.

ClinicalTrials.gov Identifier:

NCT01753167

Other Study ID Numbers:

GV28418
2012-002245-37

First Posted:

Dec 20, 2012

Last Update Posted:

Mar 8, 2017

Last Verified:

Mar 1, 2017

Additional relevant MeSH terms:

Cytomegalovirus Infections

Study Results

No Results Posted as of Mar 8, 2017