A Phase 1 Dose Escalation Study to Examine the Safety of the P2-VP8 Rotavirus Vaccine

NCT01764256 | Completed Phase 1 Results DMC

• 1 other identifier: VAC 009
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

This study will evaluate 3 doses of a new vaccine for rotavirus infection in healthy adult volunteers to determine if it is safe and if the immune systems of healthy adults respond to this vaccine.

Conditions

Rotavirus Infection

Keywords

rotavirus; vaccine

Outcome Measures

Primary Outcomes (5)

• 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.

  7 days post Vaccination #2 on Day 35

• Maximum Local or Systemic Reactogenicity After the Third 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 #3 on Day 56

Secondary Outcomes (4)

• Number and Percentage of Subjects With Anti-P2-VP8 Immunoglobulin G (IgG) and Immunoglobulin A (IgA) Seroresponses

  4 weeks post 3rd immunization (84 days)

• Geometric Mean Titer (GMT) of Anti-P2-VP8 Immunoglobulin G (IgG)

  Days 0, 28, 56 and 84 (before the first injection and 4 weeks after each injection)

• Geometric Mean Titer (GMT) of Anti-P2-VP8 Immunoglobulin A (IgA)

  Days 0, 28, 56 and 84 (before the first injection and 4 weeks after each injection)

• Number and Percentage of Subjects With Serum Neutralizing Antibody Seroresponse, by Rotavirus Strain

  4 weeks post 3rd immunization (84 days)

Study Arms (4)

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

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.

10 μg P2-VP8; 30 μg P2-VP8; 60 μg P2-VP8

placebo OTHER

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.

Placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• A qualified volunteer must be:
• Healthy male or female between 18 and 45 (inclusive) years of age at time of enrollment.
• Willing and able to give informed consent - must pass test of comprehension with \> 70% correct within two attempts.
• 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.
• 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).
• Able and willing to be contacted by telephone or text, and willing for study staff to record telephone voice or text messages as needed.

You may not qualify if:

• A qualified volunteer must not:
• Have received an investigational product during the 30 days prior to randomization.
• Intend to receive another investigational product during this study.
• Have any contraindication to parenteral injections (e.g., history of bleeding disorder).
• Have previously received a marketed or investigational rotavirus vaccine.
• Have a history of severe local or systemic reaction to any vaccine.
• Have a history of recurrent urticaria of unknown cause.
• 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.
• 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.
• Have received any vaccine within 4 weeks prior to randomization or planned vaccination through Day 84.
• Have received any blood product or any immunomodulating agent (e.g., immunoglobulin, interferon, growth factor) within 12 weeks prior to randomization.
• 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.
• Have a history of any clinically significant (in the opinion of the PI) immunosuppressive or autoimmune condition.
• Anticipate need for administration of any blood product, immunosuppressive (e.g., systemic corticosteroid), or immunomodulatory treatment during the study.
• Have a history of malignancy, excluding basal cell carcinoma.

Sponsors & Collaborators

• PATH: lead

Study Sites (1)

Center for Immunization Research

Baltimore, Maryland, 21205, United States

Location

Related Publications (1)

• 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.

  PMID: 26065919 DERIVED

MeSH Terms

Conditions

Rotavirus Infections

Condition Hierarchy (Ancestors)

Reoviridae Infections; RNA Virus Infections; Virus Diseases; Infections

Results Point of Contact

• Title: Jorge Flores
• Organization: PATH

jeflores@path.org

2028220033

Study Officials

• Clayton Harro, MD

  Johns Hopkins Bloomberg School of Hygiene and Public Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 7, 2013
• First Posted: January 9, 2013
• Study Start: December 1, 2012
• Primary Completion: June 1, 2013
• Study Completion: September 1, 2013
• Last Updated: March 12, 2019
• Results First Posted: February 15, 2019

Record last verified: 2019-02

Locations

US (1)