A Phase 1 Dose Escalation Study to Examine the Safety of... | NCT01764256

NCT01764256

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
10 μg P2-VP8	Experimental	3 doses of P2-VP8 subunit rotavirus vaccine (Lot # 1746) produced in E. coli was adsorbed onto aluminum hydroxide (0.6 mg/dose) adjuvant prior to administration. Each dose contained 10 μg of active ingredient.	Biological: P2-VP8 subunit rotavirus vaccine
30 μg P2-VP8	Experimental	3 doses of P2-VP8 subunit rotavirus vaccine (Lot # 1746) produced in E. coli was adsorbed onto aluminum hydroxide (0.6 mg/dose) adjuvant prior to administration. Each dose contained 30 μg of active ingredient.	Biological: P2-VP8 subunit rotavirus vaccine
60 μg P2-VP8	Experimental	3 doses of P2-VP8 subunit rotavirus vaccine (Lot # 1746) produced in E. coli was adsorbed onto aluminum hydroxide (0.6 mg/dose) adjuvant prior to administration. Each dose contained 60 μg of active ingredient.	Biological: P2-VP8 subunit rotavirus vaccine
Placebo	Placebo Comparator	3 doses of placebo delivered intramuscularly.	Other: placebo

Interventions

Name	Type	Description	Arm Group Labels	Other Names
P2-VP8 subunit rotavirus vaccine	Biological	P2-VP8 subunit rotavirus vaccine was made by inserting a codon optimized synthetic gene for the VP8 region of rotavirus VP4 fused to the P2 T-cell epitope of tetanus toxin into the Pj411 proprietary cloning vector developed by DNA 2.0, Menlo Park, CA. The vector carries a kanamycin resistance gene as a selection marker. The vector was transfected into the BL21 strain of E. coli. The fusion protein was purified from Isopropyl β-D-1-thiogalactopyranoside (IPTG)-induced and physically lysed cultures using standard column chromatographic techniques employing Q-Sepharose and Butyl 650 as resins in addition to ultrafiltration and diafiltration.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Maximum Severity of Adverse Events After Any Vaccination	Adverse events were collected through 28 days following the final study injection and were graded for severity. Unsolicited adverse events were also assessed for relationship to vaccine. A final follow-up contact was attempted 6 months following the final study injection to inquire about new chronic health conditions, serious health events, and hospitalizations.	6 months after final vaccination (224 days)
Maximum Local or Systemic Reactogenicity After Any Vaccination	For all cohorts, local and systemic reactogenicity data for all vaccinations were collected by subjects via diary card up to 7 days post each vaccination. Solicited systemic reactogenicity events included headache, muscle pain, fever, nausea, vomiting, fatigue, joint aches, and chills. Solicited local systemic reactogenicity events included injection site pain, tenderness, redness, swelling, itching, and local lymphadenopathy.	7 days after each vaccination (Day 7, 35, 63)
Maximum Local or Systemic Reactogenicity After the First Vaccination	For all cohorts, local and systemic reactogenicity data for all vaccinations were collected by subjects via diary card up to 7 days post each vaccination. Solicited systemic reactogenicity events included headache, muscle pain, fever, nausea, vomiting, fatigue, joint aches, and chills. Solicited local systemic reactogenicity events included injection site pain, tenderness, redness, swelling, itching, and local lymphadenopathy.	7 days post Vaccination #1 on Day 0
Maximum Local or Systemic Reactogenicity After the Second Vaccination	For all cohorts, local and systemic reactogenicity data for all vaccinations were collected by subjects via diary card up to 7 days post each vaccination. Solicited systemic reactogenicity events included headache, muscle pain, fever, nausea, vomiting, fatigue, joint aches, and chills. Solicited local systemic reactogenicity events included injection site pain, tenderness, redness, swelling, itching, and local lymphadenopathy.

Secondary Outcomes

Measure	Description	Time Frame
Number and Percentage of Subjects With Anti-P2-VP8 Immunoglobulin G (IgG) and Immunoglobulin A (IgA) Seroresponses	Seroresponse was defined as as a four-fold increase in antibody titers between baseline and 4-weeks post-third injection.	4 weeks post 3rd immunization (84 days)
Geometric Mean Titer (GMT) of Anti-P2-VP8 Immunoglobulin G (IgG)

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

A qualified volunteer must be:
1. Healthy male or female between 18 and 45 (inclusive) years of age at time of enrollment.
2. Willing and able to give informed consent - must pass test of comprehension with > 70% correct within two attempts.
3. If female and of childbearing potential, be not breastfeeding and not pregnant (based on a negative serum pregnancy test at screening and a negative urine pregnancy test during the 24 hours prior to first injection), planning to avoid pregnancy for at least 4 weeks after the last injection, and willing to use an adequate method of contraception consistently and have repeated pregnancy tests prior to second and third injections.
4. Willing to comply with study restrictions and study schedule (as evidenced by a signed informed consent form (ICF) and assessment by the Principal Investigator (PI) or designee).
5. Able and willing to be contacted by telephone or text, and willing for study staff to record telephone voice or text messages as needed.
  
  Exclusion Criteria:
A qualified volunteer must not:
1. Have received an investigational product during the 30 days prior to randomization.
2. Intend to receive another investigational product during this study.
3. Have any contraindication to parenteral injections (e.g., history of bleeding disorder).
4. Have previously received a marketed or investigational rotavirus vaccine.
5. Have a history of severe local or systemic reaction to any vaccine.
6. Have a history of recurrent urticaria of unknown cause.
7. Have a history of any allergic or infusion reaction that was severe (e.g., anaphylactic or anaphylactoid), generalized (e.g., drug rash, urticaria, angioedema) or that, in the opinion of the PI, significantly increases risk of severe local or systemic reaction to an investigative vaccine.
8. Have a history of reaction to any vaccine that, in the opinion of the PI, significantly increases risk of severe reaction to an investigative vaccine.
9. Have received any vaccine within 4 weeks prior to randomization or planned vaccination through Day 84.
10. Have received any blood product or any immunomodulating agent (e.g., immunoglobulin, interferon, growth factor) within 12 weeks prior to randomization.
11. Have received immunosuppressive medications (e.g., prolonged use of systemic corticosteroid or cytotoxic agent) within the 24 weeks prior to randomization. Eligible if a short course (≤10 days) of systemic corticosteroid concluded more than 2 weeks prior to randomization, use of inhaled corticosteroid for asthma, and use of topical corticosteroid for a skin condition.
12. Have a history of any clinically significant (in the opinion of the PI) immunosuppressive or autoimmune condition.
13. Anticipate need for administration of any blood product, immunosuppressive (e.g., systemic corticosteroid), or immunomodulatory treatment during the study.
14. Have a history of malignancy, excluding basal cell carcinoma.
15. Have Diabetes Mellitus Type I or II.
16. Have a positive test for human immunodeficiency virus 1 (HIV-1), Hepatitis B surface antigen (HBsAg) or (Hepatitis C Antibody Test) anti-HepC.
17. Have significant abnormalities in screening laboratory test results or clinical assessment as determined by the PI or by the PI in consultation with the Sponsor's medical officer.*
18. Have abnormal vital signs deemed clinically relevant by the Principle Investigator (PI).
19. Evidence of current or recent (within past 12 months) excessive alcohol consumption or drug dependence.
20. Have any condition of hand, arm or related lymph nodes that may confound post-dose assessments.
21. Have any condition (medical, psychiatric or behavioral) that, in the opinion of the PI, would increase the volunteer's health risks in study participation or would increase the risk of not achieving the study's objectives

Name	Affiliation	Role
Clayton Harro, MD	Johns Hopkins Bloomberg School of Hygiene and Public Health	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Center for Immunization Research		Baltimore	Maryland	21205	United States

PubMed Identifier	Type	Citation	Retractions
26065919	Derived	Fix AD, Harro C, McNeal M, Dally L, Flores J, Robertson G, Boslego JW, Cryz S. Safety and immunogenicity of a parenterally administered rotavirus VP8 subunit vaccine in healthy adults. Vaccine. 2015 Jul 17;33(31):3766-72. doi: 10.1016/j.vaccine.2015.05.024. Epub 2015 Jun 8.

Arm/Group Information

ID	Title	Description
FG000	Placebo	3 doses of placebo delivered intramuscularly. placebo: Sodium Chloride 0.9%, USP for Injection was used to dilute the active P2-VP8 vaccine to final dosing concentration and was used for the Placebo for the study.
FG001	10 μg P2-VP8	3 doses of P2-VP8 subunit rotavirus vaccine (Lot # 1746) produced in E. coli was adsorbed onto aluminum hydroxide (0.6 mg/dose) adjuvant prior to administration. Each dose contained 10 μg of active ingredient. P2-VP8 subunit rotavirus vaccine: P2-VP8 subunit rotavirus vaccine was made by inserting a codon optimized synthetic gene for the VP8 region of rotavirus VP4 fused to the P2 T-cell epitope of tetanus toxin into the Pj411 proprietary cloning vector developed by DNA 2.0, Menlo Park, CA. The vector carries a kanamycin resistance gene as a selection marker. The vector was transfected into the BL21 strain of E. coli. The fusion protein was purified from Isopropyl β-D-1-thiogalactopyranoside (IPTG)-induced and physically lysed cultures using standard column chromatographic techniques employing Q-Sepharose and Butyl 650 as resins in addition to ultrafiltration and diafiltration.
FG002	30 μg P2-VP8	3 doses of P2-VP8 subunit rotavirus vaccine (Lot # 1746) produced in E. coli was adsorbed onto aluminum hydroxide (0.6 mg/dose) adjuvant prior to administration. Each dose contained 30 μg of active ingredient. P2-VP8 subunit rotavirus vaccine: P2-VP8 subunit rotavirus vaccine was made by inserting a codon optimized synthetic gene for the VP8 region of rotavirus VP4 fused to the P2 T-cell epitope of tetanus toxin into the Pj411 proprietary cloning vector developed by DNA 2.0, Menlo Park, CA. The vector carries a kanamycin resistance gene as a selection marker. The vector was transfected into the BL21 strain of E. coli. The fusion protein was purified from Isopropyl β-D-1-thiogalactopyranoside (IPTG)-induced and physically lysed cultures using standard column chromatographic techniques employing Q-Sepharose and Butyl 650 as resins in addition to ultrafiltration and diafiltration.
FG003	60 μg P2-VP8	3 doses of P2-VP8 subunit rotavirus vaccine (Lot # 1746) produced in E. coli was adsorbed onto aluminum hydroxide (0.6 mg/dose) adjuvant prior to administration. Each dose contained 60 μg of active ingredient. P2-VP8 subunit rotavirus vaccine: P2-VP8 subunit rotavirus vaccine was made by inserting a codon optimized synthetic gene for the VP8 region of rotavirus VP4 fused to the P2 T-cell epitope of tetanus toxin into the Pj411 proprietary cloning vector developed by DNA 2.0, Menlo Park, CA. The vector carries a kanamycin resistance gene as a selection marker. The vector was transfected into the BL21 strain of E. coli. The fusion protein was purified from Isopropyl β-D-1-thiogalactopyranoside (IPTG)-induced and physically lysed cultures using standard column chromatographic techniques employing Q-Sepharose and Butyl 650 as resins in addition to ultrafiltration and diafiltration.

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	10 μg P2-VP8	3 doses of P2-VP8 subunit rotavirus vaccine (Lot # 1746) produced in E. coli was adsorbed onto aluminum hydroxide (0.6 mg/dose) adjuvant prior to administration. Each dose contained 10 μg of active ingredient. P2-VP8 subunit rotavirus vaccine: P2-VP8 subunit rotavirus vaccine was made by inserting a codon optimized synthetic gene for the VP8 region of rotavirus VP4 fused to the P2 T-cell epitope of tetanus toxin into the Pj411 proprietary cloning vector developed by DNA 2.0, Menlo Park, CA. The vector carries a kanamycin resistance gene as a selection marker. The vector was transfected into the BL21 strain of E. coli. The fusion protein was purified from Isopropyl β-D-1-thiogalactopyranoside (IPTG)-induced and physically lysed cultures using standard column chromatographic techniques employing Q-Sepharose and Butyl 650 as resins in addition to ultrafiltration and diafiltration.

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Maximum Severity of Adverse Events After Any Vaccination

Adverse events were collected through 28 days following the final study injection and were graded for severity. Unsolicited adverse events were also assessed for relationship to vaccine. A final follow-up contact was attempted 6 months following the final study injection to inquire about new chronic health conditions, serious health events, and hospitalizations.

Posted

Count of Participants

Participants

6 months after final vaccination (224 days)

ID	Title	Description
OG000	10 μg P2-VP8	3 doses of P2-VP8 subunit rotavirus vaccine (Lot # 1746) produced in E. coli was adsorbed onto aluminum hydroxide (0.6 mg/dose) adjuvant prior to administration. Each dose contained 10 μg of active ingredient. P2-VP8 subunit rotavirus vaccine: P2-VP8 subunit rotavirus vaccine was made by inserting a codon optimized synthetic gene for the VP8 region of rotavirus VP4 fused to the P2 T-cell epitope of tetanus toxin into the Pj411 proprietary cloning vector developed by DNA 2.0, Menlo Park, CA. The vector carries a kanamycin resistance gene as a selection marker. The vector was transfected into the BL21 strain of E. coli. The fusion protein was purified from Isopropyl β-D-1-thiogalactopyranoside (IPTG)-induced and physically lysed cultures using standard column chromatographic techniques employing Q-Sepharose and Butyl 650 as resins in addition to ultrafiltration and diafiltration.

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	10 μg P2-VP8	3 doses of P2-VP8 subunit rotavirus vaccine (Lot # 1746) produced in E. coli was adsorbed onto aluminum hydroxide (0.6 mg/dose) adjuvant prior to administration. Each dose contained 10 μg of active ingredient. P2-VP8 subunit rotavirus vaccine: P2-VP8 subunit rotavirus vaccine was made by inserting a codon optimized synthetic gene for the VP8 region of rotavirus VP4 fused to the P2 T-cell epitope of tetanus toxin into the Pj411 proprietary cloning vector developed by DNA 2.0, Menlo Park, CA. The vector carries a kanamycin resistance gene as a selection marker. The vector was transfected into the BL21 strain of E. coli. The fusion protein was purified from Isopropyl β-D-1-thiogalactopyranoside (IPTG)-induced and physically lysed cultures using standard column chromatographic techniques employing Q-Sepharose and Butyl 650 as resins in addition to ultrafiltration and diafiltration.

ID	Term
D012088	Reoviridae Infections
D012327	RNA Virus Infections
D014777	Virus Diseases
D007239	Infections