Safety, Reactogenicity and Immunogenicity of Heat-stable Rotavirus Vaccine (HSRV) in Adults and Infants

NCT02728869 | Completed Phase 1 DMC

• 1 other identifier: HL/RVV/CT1/15
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Rotaviruses are the leading cause of severe, dehydrating diarrhoea and related deaths in children aged less than 5 years worldwide and are reported to infect nearly every child by the age of 5 years. About 90% of all rotavirus-associated fatalities occur in low income countries in Africa and Asia and are related to poor health care. In view of high global RVGE burden, the World Health Organization (WHO) on 5th June 2009, recommended the inclusion of rotavirus vaccine in all the national immunization programs. Currently available rotavirus vaccines, RotaTeq® and Rotarix®, are WHO prequalified vaccines which are stable for recommended duration at storage temperature between 2-8 °C. However, if these vaccine are exposed to temperatures above 30 °C, the vaccine has to be discarded due to lost potency. It is very difficult to maintain the cold chain required to conserve the vaccine potency particularly in developing and low income countries, resulting in large amount of vaccine being wasted and in worst case scenario, endangering the lives of potential recipients. The WHO estimates that nearly half of freeze-dried and quarter of liquid vaccines are wasted each year. One of the biggest contributors to this wastage is disruption of the cold chain systems. Hilleman Labs new Rotavirus vaccine is a lyophilized heat stable rotavirus vaccine comprising of five live attenuated reassortant rotaviruses similar to RotaTeq®. The new heat stable rotavirus vaccine (HSRV) formulation offers a stability profile of 9 months at 45 °C and 12 months at 37 °C. This new heat stable formulation (HSRV) could be transported in non-refrigerated supply chain significantly reducing the cost and complications associated with transporting vaccine to remote corners of the developing world. Heat-stable rotavirus vaccine (HSRV) has a potential to sustain high temperatures frequently encountered in regions where majority of rotavirus burden exists and has potential to partially or completely eliminate cold chain dependence. The current study has been designed to test for the first time in humans, the safety and tolerability of the new heat stable rotavirus vaccine (HSRV) in adults; followed by safety and immunogenicity in infants of age 6-8 weeks, as compared to the licensed RotaTeq® vaccine.

Conditions

Rotavirus Gastroenteritis

Outcome Measures

Primary Outcomes (4)

• Any adverse event in adult cohort

  Up to two weeks after single dose of vaccine or placebo

• Serious adverse events in adult cohort

  Up to two weeks after single dose of vaccine or placebo

• Any adverse event in infant cohort

  Up to one month after 3 doses of vaccine or active control

• Serious adverse events in infant cohort

  Up to one month after 3 doses of vaccine or active control

Secondary Outcomes (3)

• Anti-Rotavirus IgA sero-response rate in infant cohort

  One month after third dose of vaccine or active control

• Viral shedding after single dose of vaccine or placebo in adults

  Up to 7 days after single dose of vaccine or placebo

• Viral shedding in infants after each dose of vaccine or active control in infants

  Up to 7 days after each dose of vaccine

Study Arms (4)

Heat Stable Rotavirus (HSRV) Vaccine

EXPERIMENTAL

25 healthy adults who will be administered a single dose of test HSRV vaccine

Biological: Heat Stable Rotavirus (HSRV) Vaccine

Placebo for Heatstable Rotavirus vaccine

PLACEBO COMPARATOR

25 healthy adults who will be administered a single dose of placebo

Biological: Placebo for Heatstable Rotavirus vaccine

Heat Stable Rotavirus Vaccine

EXPERIMENTAL

25 healthy infants who will be administered 3-doses of test HSRV vaccine spaced at 4-week intervals

Biological: Heat Stable Rotavirus (HSRV) Vaccine

RotaTeq

ACTIVE COMPARATOR

25 healthy infants who will be administered 3-doses of comparator Rotateq® vaccine spaced at 4-week intervals

Biological: RotaTeq®

Interventions

Heat Stable Rotavirus (HSRV) Vaccine BIOLOGICAL

It is a lyophilized live attenuated pentavalent (G1-G4 and P1\[8\]) heat-stable rotavirus vaccine (HSRV) comprising of all the five rotavirus strains as in licensed RotaTeq® vaccine for protection against rotavirus infection

Also known as: HSRV

Heat Stable Rotavirus (HSRV) Vaccine; Heat Stable Rotavirus Vaccine

Placebo for Heatstable Rotavirus vaccine BIOLOGICAL

It is a lyophilized formulation comprising of all the inactive ingredients as in heat stable rotavirus vaccine without any rotavirus

Also known as: Placebo

Placebo for Heatstable Rotavirus vaccine

RotaTeq® BIOLOGICAL

It is a pentavalent human-bovine (WC3) reassortant live-attenuated, oral vaccine developed by Merck Research Co., West Point, Pennsylvania, USA. This vaccine contains five live reassortant rotaviruses. Four reassortant rotaviruses express the VP7 protein (G1, G2, G3, or G4) from the human rotavirus parent strain and the attachment protein (P7\[5\]) from bovine rotavirus parent strain WC3. The fifth reassortant virus expresses the attachment protein (P1A\[8\]) from the human rotavirus parent strain and the outer capsid protein G6 from the bovine rotavirus parent strain.

Also known as: Active Comparator

RotaTeq

Eligibility Criteria

• Age: 6 Weeks - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Healthy Adults:
• Healthy adult subjects of either sex, between 18 to 45 years of age;
• No apparent signs or symptoms of ill health;
• Subjects properly informed about the study and having signed the informed consent form (ICF). In case of subjects' inability to read or write, having had the ICF explained to them in the presence of a study independent witness and the witness having signed the ICF;
• Subjects' availability for the entire period of the study and reachability by study staff for post vaccination follow-up.
• Healthy Infants:
• Healthy infants of either sex, 6-8 weeks of age at the time of enrollment;
• Born after a gestational period of 36-42 weeks with birth weight ≥ 2kg;
• Father, mother or other legally authorized representative (guardian) properly informed about the study and having signed the informed consent form (ICF). In case of father's, mother's or other legally acceptable representative's (guardian) inability to read or write, having had the ICF explained to them in the presence of a study independent witness and the witness having signed the ICF;
• Infant/Parents' or guardian's availability for the entire period of the study and reachability by study staff for post-vaccination follow-up.

You may not qualify if:

• Healthy adults:
• Known or suspected impairment of immunological function; and known immunosuppressed family members/household contacts
• Known hypersensitivity to any component of the rotavirus vaccine;
• Fever, with axillary temperature ≥38.1 oC (≥100.5 oF) as measured by study staff;
• History of chronic diarrhea;
• Clinical evidence of active gastrointestinal illness;
• Receipt of any IM, oral, or IV corticosteroid treatment in the past 30 days;
• Subjects' suspected to be HIV, HBV or HCV positive from the available clinical history;
• Any subject who cannot be adequately followed for safety assessment;
• Any conditions which, in the opinion of the investigator, might interfere with the evaluation of the study objectives;
• Subject's inability to maintain diary card;
• Participation in another clinical trial investigating a vaccine, drug, medical device or medicinal procedure in the 4 weeks preceding the current vaccination trial;
• Planned participation in another clinical trial during the present trial period;
• Subjects identified as employees of the investigator or study center, with direct involvement in the proposed study or studies under the direction of that investigator or study center as well as children, adopted or natural, of the employees or Investigator.
• Healthy Infants:

Sponsors & Collaborators

• MSD Wellcome Trust Hilleman Laboratories Pvt. Ltd.: lead
• Parexel: collaborator

Study Sites (1)

Icddr,B

Dhaka, 1212, Bangladesh

Location

Related Publications (1)

• Kanchan V, Zaman K, Aziz AB, Zaman SF, Zaman F, Haque W, Khanam M, Karim MM, Kale S, Ali SK, Goveia MG, Kaplan SS, Gill D, Khan WA, Yunus M, Singh A, Clemens JD. A randomized Phase I/II study to evaluate safety and reactogenicity of a heat-stable rotavirus vaccine in healthy adults followed by evaluation of the safety, reactogenicity, and immunogenicity in infants. Hum Vaccin Immunother. 2020 Mar 3;16(3):693-702. doi: 10.1080/21645515.2019.1664239. Epub 2019 Oct 29.

  PMID: 31526218 DERIVED

MeSH Terms

Interventions

Vaccines; RotaTeq

Intervention Hierarchy (Ancestors)

Biological Products; Complex Mixtures

Study Officials

• K Zaman, MBBS, PhD

  International Center for Diarrheal Disease Research, Bangladesh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 28, 2016
• First Posted: April 5, 2016
• Study Start: June 1, 2016
• Primary Completion: March 1, 2017
• Study Completion: April 1, 2017
• Last Updated: August 21, 2017

Record last verified: 2017-08

Locations

BA (1)