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Assessment of CR6261, a Monoclonal Antibody Against the Influenza A Virus

Primary Purpose

Influenza

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
CR6261 2 mg/kg
CR6261 5 mg/kg
CR6261 15 mg/kg
CR6261 30 mg/kg
CR6261 50 mg/kg
Placebo
Sponsored by
Crucell Holland BV
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Influenza focused on measuring Influenza, Virus, Monoclonal, Antibody, Immunization, Treatment

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesAccepts Healthy Volunteers

INCLUSION CRITERIA

  1. Adult male and female subjects aged 18 to 50 years on Study Day 1.
  2. Body mass index between 18 and 30 (kg/m2) by nomogram or calculation; body weight between 50 kg and 100 kg.
  3. Has acceptable blood pressure and heart rate parameters within the normal limits (systolic = 88-140 mmHg; diastolic = 50 to <90 mmHg; heart rate = 46 to 100 bpm).
  4. Healthy as determined by pre-study medical history, physical examination, and laboratory assessments.
  5. Able and willing to give written informed consent.
  6. Has the ability to complete the follow-up period of 75 days as required by the protocol.
  7. Subjects must agree to abstain from alcohol intake 24 hours before administration of study drug, during the inpatient period of the study and 24 hours prior to all other outpatient clinic visits.
  8. Subjects must agree to not use OTC medications (including aspirin, decongestants, antihistamines and other NSAIDs), and herbal medication (including, but not limited to, herbal tea, St. John's Wort), within 14 days prior to study drug administration through the final follow-up visit, unless approved by the investigator and medical monitor. Occasional use of acetaminophen/paracetamol at recommended doses (≤ 1 gram/6 hours and ≤ 4 grams/day) and continued pre-existing use of vitamins or multivitamins at recommended doses is allowed.
  9. Female subjects must:

    • Be surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal ligation, or otherwise be incapable of pregnancy), or
    • If heterosexually active, use two effective methods of birth control, including hormonal prescription oral contraceptives, contraceptive injections, contraceptive patch, contraceptive ring, intrauterine device, barrier method (e.g. condoms, diaphragm, or cervical cap), or spermicidal foam, cream, or gel), or
    • Confirm male partner sterilization, or
    • Not be heterosexually active Note: women who are not heterosexually active at screening must agree to utilize two effective methods of birth control if they become heterosexually active during their participation in the study.

    Women must agree to continue using these methods of contraception throughout the study.

  10. Females must have a negative urine pregnancy test at both screening and baseline.
  11. If a man who is able to father a child and sexually active with a female of childbearing potential, he must agree to use a double barrier method of birth control (e.g. condom with spermicidal foam, cream, or gel) and to not donate sperm during the study.
  12. Subjects must agree to avoid strenuous exercise (e.g. long distance running >5 km/day, weight lifting, or any physical activity to which the subject is not accustomed) while confined to the Clinical Unit and for at least 72 hours prior to study drug administration and follow up visits.

EXCLUSION CRITERIA

  1. Acute illness at the time of entry into the study (Study Day 1).
  2. Temperature >99.5oF (37.5oC) at randomization.
  3. Presence of a significant infection or known inflammatory process during screening or at the time of randomization.
  4. Presence of acute gastrointestinal symptoms during screening or at the time of randomization (e.g. nausea, vomiting, diarrhea, or heartburn).
  5. A diagnosis of influenza infection or any constellation of clinical symptoms consistent with influenza infection (e.g. fever, myalgias, headache, fatigue, non-productive cough, sore throat, and/or rhinorrhea) within 14 days prior to Study Day 1.
  6. Received any live virus or bacterial vaccinations within 3 months prior to screening or are expected to receive any live virus or bacterial vaccinations during the study.
  7. Received inactivated influenza vaccines within 2 weeks of Study Day 1 or are expected to receive an inactivated influenza vaccine during the study.
  8. Any chronic condition requiring prescription or over-the-counter medicine, with the exception of vitamins.
  9. Chronic (longer than 14 days) administration of immunosuppressants or other immune modifying drugs within 6 months before administration of the investigational product; oral corticosteroids in dosages of < 0.5 mg/kg/d prednisolone or equivalent and inhaled/nasally/topically administered corticosteroids are permitted.
  10. Antibiotic therapy within 7 days before Study Day 1.
  11. History and/or presence of any clinically significant disease or disorder such as cardiovascular, pulmonary, renal, hepatic, neurological, gastrointestinal and psychiatric/mental disease/disorders, which, in the opinion of the Principal Investigator may either put the subject at risk because of participation in the study, influence the results of the study or the subject's ability to participate in the study.
  12. Previous medical history that may compromise the safety of the subject in the study.
  13. Positive serology for the human immunodeficiency virus (HIV) 1 or 2 antibody, hepatitis C virus antibody or hepatitis B surface antigen.
  14. History of a previous severe allergic reaction with generalized urticaria, angioedema, or anaphylaxis.
  15. Known or suspected hypersensitivity to any CR6261 excipients (Sucrose, L-Histidine L-Histidine Monohydrochloride, Polysorbate 20).
  16. A history of alcohol or drug abuse within the past 2 years as according to DSM IV.
  17. Positive urine test for illicit drugs (opiates, cocaine, amphetamines) during screening and admission (Day -1).
  18. Subjects who report current tobacco use of more than 10 cigarettes or 2 cigars per day at screening or anticipate use exceeding this amount at any time during the study.
  19. Receipt of any other investigational product within 1 month or 5 half-lives (whichever is longer) before administration of the study investigational product.
  20. Participation in any clinical study involving receipt of investigational product, blood or blood products, or donation of blood throughout the duration of the study.
  21. Received antibody or biologic therapy (e.g. Ig products, mAbs, or antibody fragments).
  22. Subjects who have donated and/or received any blood or blood products within 3 months before administration of the study investigational product or planned donation/receipt throughout the course of the study.
  23. Subjects who cannot communicate reliably with the investigator.
  24. Any condition that in the opinion of the investigator would complicate or compromise the study, or the well being of the subject.
  25. Employee at the clinic, or spouse/relative of the investigator or employees.
  26. Has experienced an anaphylactic reaction to latex.
  27. Have currently or a past history of thrombocytopenia or bleeding abnormality.
  28. Is unable or unwilling to undergo multiple venipunctures because of poor tolerability or lack of easy access to veins.
  29. Female subjects who are breastfeeding.
  30. Drinks more than 1200 mL (or 5 cups of 240 mL per cup) of tea/coffee/cocoa/cola or other caffeinated beverage per day more than one day per week in the 2 weeks before screening.
  31. ECG findings (Screening or Day-1):

    • QTc interval >450 msec;
    • evidence of second- or third-degree atrioventricular (AV) block;
    • pathological Q-waves (defined as Q-wave >40 msec or depth greater than 0.4 - 0.5 mV);
    • evidence of ventricular pre-excitation;
    • electrocardiographic evidence of complete left bundle branch block, right bundle branch block (RBBB), incomplete LBBB;
    • intraventricular conduction delay with QRS duration >120 msec.
  32. Laboratory assessments (Screening or Day -1):

    • Hemoglobin below the lower limit of normal (LLN); a lower limit of 13.6 g/dL in males is acceptable;
    • Platelet count, absolute neutrophil count (ANC), or absolute lymphocyte count below LLN (ANC of 1.3 x 10³/µL is acceptable lower limit for African Americans);
    • White blood cell count above the upper limit of normal (ULN) or below the LLN (3.2 x 10³/µL is acceptable lower limit for African Americans);
    • Creatinine above the ULN;
    • PT or PTT above the ULN;
    • ALT, AST, GGTP, ALP, amylase, lipase, or total bilirubin ≥ 1.1 times the ULN (values below the LLN are not considered clinically significant).

Sites / Locations

  • Quintiles Early Clinical Development

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm 11

Arm 12

Arm Type

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Arm Label

Cohort 1: CR6261

Cohort 1: Placebo

Cohort 2: CR6261

Cohort 2: Placebo

Cohort 3: CR6261

Cohort 3: Placebo

Cohort 4: CR6261

Cohort 4: Placebo

Cohort 5: CR6261

Cohort 5: Placebo

Cohort 6: CR6261

Cohort 6 Placebo

Arm Description

2 mg/kg CR6261

5% dextrose in water

5 mg/kg CR6261

5% dextrose in water

15 mg/kg CR6261

5% dextrose in water

30 mg/kg CR6261

5% dextrose in water

50 mg/kg CR6261

5% dextrose in water

30 mg/kg CR6261

5% dextrose in water

Outcomes

Primary Outcome Measures

Adverse events and changes in laboratory parameters and vital signs as measures of safety and tolerability of single escalating doses of CR6261

Secondary Outcome Measures

Assessment of pharmacokinetics of single escalating doses of CR6261
Pharmacokinetic parameters include area under the serum concentration-time curve from zero to the time of the last measurable concentration (AUC0-t), area under the serum concentration-time curve from zero to infinity (AUC0-inf), maximum concentration (Cmax), time of Cmax (tmax), systemic clearance (CL), terminal elimination half life (t1/2), etc.
Assessment of antibodies binding to CR6261 as a measure of immunogenicity of single escalating doses of CR6261

Full Information

First Posted
July 28, 2011
Last Updated
December 18, 2013
Sponsor
Crucell Holland BV
Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
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1. Study Identification

Unique Protocol Identification Number
NCT01406418
Brief Title
Assessment of CR6261, a Monoclonal Antibody Against the Influenza A Virus
Official Title
A Phase I, Randomized, Double-Blind, Placebo-Controlled Study in Healthy Subjects to Assess the Safety, Tolerability, Pharmacokinetics, and Immunogenicity of CR6261, a Monoclonal Antibody Against Influenza A Viruses, Following Single-Dose Intravenous Administration
Study Type
Interventional

2. Study Status

Record Verification Date
December 2013
Overall Recruitment Status
Completed
Study Start Date
February 2013 (undefined)
Primary Completion Date
November 2013 (Actual)
Study Completion Date
November 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Crucell Holland BV
Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to assess in healthy subjects the safety, tolerability, pharmacokinetics and immunogenicity of single escalating doses of CR6261, a monoclonal antibody against influenza A viruses.
Detailed Description
This randomized, double-blind, placebo-controlled dose escalation study will enroll up to 6 cohorts of healthy subjects. Eight subjects will be enrolled in each cohort (1 to 5) and will receive a single 2-hour intravenous infusion of CR6261 (6 subjects) or placebo (2 subjects) on Day 1. Subjects will be dosed in pairs of two. Once all subjects in a cohort have completed Study Day 8, the preliminary safety data will be reviewed. Provided that no safety issues are identified, dose escalation to the subsequent cohort may be permitted. To obtain additional data at the 30 mg/kg dose level, a sixth cohort will be enrolled after the preliminary safety and tolerability of the 30 mg/kg dose in Cohort 4 is demonstrated. Cohort 6 will be comprised of 24 subjects (randomized 5 : 1 to CR6261 or placebo) following the same visit schedule as subjects in Cohorts 1-5.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Influenza
Keywords
Influenza, Virus, Monoclonal, Antibody, Immunization, Treatment

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
64 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1: CR6261
Arm Type
Experimental
Arm Description
2 mg/kg CR6261
Arm Title
Cohort 1: Placebo
Arm Type
Placebo Comparator
Arm Description
5% dextrose in water
Arm Title
Cohort 2: CR6261
Arm Type
Experimental
Arm Description
5 mg/kg CR6261
Arm Title
Cohort 2: Placebo
Arm Type
Placebo Comparator
Arm Description
5% dextrose in water
Arm Title
Cohort 3: CR6261
Arm Type
Experimental
Arm Description
15 mg/kg CR6261
Arm Title
Cohort 3: Placebo
Arm Type
Placebo Comparator
Arm Description
5% dextrose in water
Arm Title
Cohort 4: CR6261
Arm Type
Experimental
Arm Description
30 mg/kg CR6261
Arm Title
Cohort 4: Placebo
Arm Type
Placebo Comparator
Arm Description
5% dextrose in water
Arm Title
Cohort 5: CR6261
Arm Type
Experimental
Arm Description
50 mg/kg CR6261
Arm Title
Cohort 5: Placebo
Arm Type
Placebo Comparator
Arm Description
5% dextrose in water
Arm Title
Cohort 6: CR6261
Arm Type
Experimental
Arm Description
30 mg/kg CR6261
Arm Title
Cohort 6 Placebo
Arm Type
Placebo Comparator
Arm Description
5% dextrose in water
Intervention Type
Biological
Intervention Name(s)
CR6261 2 mg/kg
Intervention Description
Administered as a single 2-hour intravenous infusion
Intervention Type
Biological
Intervention Name(s)
CR6261 5 mg/kg
Intervention Description
Administered as a single 2-hour intravenous infusion
Intervention Type
Biological
Intervention Name(s)
CR6261 15 mg/kg
Intervention Description
Administered as a single 2-hour intravenous infusion
Intervention Type
Biological
Intervention Name(s)
CR6261 30 mg/kg
Intervention Description
Administered as a single 2-hour intravenous infusion
Intervention Type
Biological
Intervention Name(s)
CR6261 50 mg/kg
Intervention Description
Administered as a single 2-hour intravenous infusion
Intervention Type
Biological
Intervention Name(s)
Placebo
Intervention Description
Administered as a single 2-hour intravenous infusion
Primary Outcome Measure Information:
Title
Adverse events and changes in laboratory parameters and vital signs as measures of safety and tolerability of single escalating doses of CR6261
Time Frame
From baseline to 75 days post-dose
Secondary Outcome Measure Information:
Title
Assessment of pharmacokinetics of single escalating doses of CR6261
Description
Pharmacokinetic parameters include area under the serum concentration-time curve from zero to the time of the last measurable concentration (AUC0-t), area under the serum concentration-time curve from zero to infinity (AUC0-inf), maximum concentration (Cmax), time of Cmax (tmax), systemic clearance (CL), terminal elimination half life (t1/2), etc.
Time Frame
From baseline to 75 days post-dose
Title
Assessment of antibodies binding to CR6261 as a measure of immunogenicity of single escalating doses of CR6261
Time Frame
From baseline to 75 days post-dose

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
INCLUSION CRITERIA Adult male and female subjects aged 18 to 50 years on Study Day 1. Body mass index between 18 and 30 (kg/m2) by nomogram or calculation; body weight between 50 kg and 100 kg. Has acceptable blood pressure and heart rate parameters within the normal limits (systolic = 88-140 mmHg; diastolic = 50 to <90 mmHg; heart rate = 46 to 100 bpm). Healthy as determined by pre-study medical history, physical examination, and laboratory assessments. Able and willing to give written informed consent. Has the ability to complete the follow-up period of 75 days as required by the protocol. Subjects must agree to abstain from alcohol intake 24 hours before administration of study drug, during the inpatient period of the study and 24 hours prior to all other outpatient clinic visits. Subjects must agree to not use OTC medications (including aspirin, decongestants, antihistamines and other NSAIDs), and herbal medication (including, but not limited to, herbal tea, St. John's Wort), within 14 days prior to study drug administration through the final follow-up visit, unless approved by the investigator and medical monitor. Occasional use of acetaminophen/paracetamol at recommended doses (≤ 1 gram/6 hours and ≤ 4 grams/day) and continued pre-existing use of vitamins or multivitamins at recommended doses is allowed. Female subjects must: Be surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal ligation, or otherwise be incapable of pregnancy), or If heterosexually active, use two effective methods of birth control, including hormonal prescription oral contraceptives, contraceptive injections, contraceptive patch, contraceptive ring, intrauterine device, barrier method (e.g. condoms, diaphragm, or cervical cap), or spermicidal foam, cream, or gel), or Confirm male partner sterilization, or Not be heterosexually active Note: women who are not heterosexually active at screening must agree to utilize two effective methods of birth control if they become heterosexually active during their participation in the study. Women must agree to continue using these methods of contraception throughout the study. Females must have a negative urine pregnancy test at both screening and baseline. If a man who is able to father a child and sexually active with a female of childbearing potential, he must agree to use a double barrier method of birth control (e.g. condom with spermicidal foam, cream, or gel) and to not donate sperm during the study. Subjects must agree to avoid strenuous exercise (e.g. long distance running >5 km/day, weight lifting, or any physical activity to which the subject is not accustomed) while confined to the Clinical Unit and for at least 72 hours prior to study drug administration and follow up visits. EXCLUSION CRITERIA Acute illness at the time of entry into the study (Study Day 1). Temperature >99.5oF (37.5oC) at randomization. Presence of a significant infection or known inflammatory process during screening or at the time of randomization. Presence of acute gastrointestinal symptoms during screening or at the time of randomization (e.g. nausea, vomiting, diarrhea, or heartburn). A diagnosis of influenza infection or any constellation of clinical symptoms consistent with influenza infection (e.g. fever, myalgias, headache, fatigue, non-productive cough, sore throat, and/or rhinorrhea) within 14 days prior to Study Day 1. Received any live virus or bacterial vaccinations within 3 months prior to screening or are expected to receive any live virus or bacterial vaccinations during the study. Received inactivated influenza vaccines within 2 weeks of Study Day 1 or are expected to receive an inactivated influenza vaccine during the study. Any chronic condition requiring prescription or over-the-counter medicine, with the exception of vitamins. Chronic (longer than 14 days) administration of immunosuppressants or other immune modifying drugs within 6 months before administration of the investigational product; oral corticosteroids in dosages of < 0.5 mg/kg/d prednisolone or equivalent and inhaled/nasally/topically administered corticosteroids are permitted. Antibiotic therapy within 7 days before Study Day 1. History and/or presence of any clinically significant disease or disorder such as cardiovascular, pulmonary, renal, hepatic, neurological, gastrointestinal and psychiatric/mental disease/disorders, which, in the opinion of the Principal Investigator may either put the subject at risk because of participation in the study, influence the results of the study or the subject's ability to participate in the study. Previous medical history that may compromise the safety of the subject in the study. Positive serology for the human immunodeficiency virus (HIV) 1 or 2 antibody, hepatitis C virus antibody or hepatitis B surface antigen. History of a previous severe allergic reaction with generalized urticaria, angioedema, or anaphylaxis. Known or suspected hypersensitivity to any CR6261 excipients (Sucrose, L-Histidine L-Histidine Monohydrochloride, Polysorbate 20). A history of alcohol or drug abuse within the past 2 years as according to DSM IV. Positive urine test for illicit drugs (opiates, cocaine, amphetamines) during screening and admission (Day -1). Subjects who report current tobacco use of more than 10 cigarettes or 2 cigars per day at screening or anticipate use exceeding this amount at any time during the study. Receipt of any other investigational product within 1 month or 5 half-lives (whichever is longer) before administration of the study investigational product. Participation in any clinical study involving receipt of investigational product, blood or blood products, or donation of blood throughout the duration of the study. Received antibody or biologic therapy (e.g. Ig products, mAbs, or antibody fragments). Subjects who have donated and/or received any blood or blood products within 3 months before administration of the study investigational product or planned donation/receipt throughout the course of the study. Subjects who cannot communicate reliably with the investigator. Any condition that in the opinion of the investigator would complicate or compromise the study, or the well being of the subject. Employee at the clinic, or spouse/relative of the investigator or employees. Has experienced an anaphylactic reaction to latex. Have currently or a past history of thrombocytopenia or bleeding abnormality. Is unable or unwilling to undergo multiple venipunctures because of poor tolerability or lack of easy access to veins. Female subjects who are breastfeeding. Drinks more than 1200 mL (or 5 cups of 240 mL per cup) of tea/coffee/cocoa/cola or other caffeinated beverage per day more than one day per week in the 2 weeks before screening. ECG findings (Screening or Day-1): QTc interval >450 msec; evidence of second- or third-degree atrioventricular (AV) block; pathological Q-waves (defined as Q-wave >40 msec or depth greater than 0.4 - 0.5 mV); evidence of ventricular pre-excitation; electrocardiographic evidence of complete left bundle branch block, right bundle branch block (RBBB), incomplete LBBB; intraventricular conduction delay with QRS duration >120 msec. Laboratory assessments (Screening or Day -1): Hemoglobin below the lower limit of normal (LLN); a lower limit of 13.6 g/dL in males is acceptable; Platelet count, absolute neutrophil count (ANC), or absolute lymphocyte count below LLN (ANC of 1.3 x 10³/µL is acceptable lower limit for African Americans); White blood cell count above the upper limit of normal (ULN) or below the LLN (3.2 x 10³/µL is acceptable lower limit for African Americans); Creatinine above the ULN; PT or PTT above the ULN; ALT, AST, GGTP, ALP, amylase, lipase, or total bilirubin ≥ 1.1 times the ULN (values below the LLN are not considered clinically significant).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Eleanor Lisbon, MD
Organizational Affiliation
Quintiles, Inc.
Official's Role
Principal Investigator
Facility Information:
Facility Name
Quintiles Early Clinical Development
City
Overland Park
State/Province
Kansas
ZIP/Postal Code
66211
Country
United States

12. IPD Sharing Statement

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Assessment of CR6261, a Monoclonal Antibody Against the Influenza A Virus

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