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

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ClinicalTrials.gov Identifier: NCT02728869
Recruitment Status : Completed
First Posted : April 5, 2016
Last Update Posted : August 21, 2017
Sponsor:
Collaborator:
Parexel
Information provided by (Responsible Party):
MSD Wellcome Trust Hilleman Laboratories Pvt. Ltd.

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.


Condition or disease Intervention/treatment Phase
Rotavirus Gastroenteritis Biological: Heat Stable Rotavirus (HSRV) Vaccine Biological: Placebo for Heatstable Rotavirus vaccine Biological: RotaTeq® Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Prevention
Official Title: A Randomized Phase I/II Study to Evaluate Safety & Reactogenicity of Heat Stable Rotavirus Vaccine, in Healthy Adult; Followed by Evaluation of the Safety, Reactogenicity & Immunogenicity of a 3-dose Series in Infants Age 6-8 Weeks
Actual Study Start Date : June 2016
Actual Primary Completion Date : March 2017
Actual Study Completion Date : April 2017

Arm Intervention/treatment
Experimental: Heat Stable Rotavirus (HSRV) Vaccine
25 healthy adults who will be administered a single dose of test HSRV vaccine
Biological: Heat Stable Rotavirus (HSRV) Vaccine
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
Other Name: HSRV

Placebo Comparator: Placebo for Heatstable Rotavirus vaccine
25 healthy adults who will be administered a single dose of placebo
Biological: Placebo for Heatstable Rotavirus vaccine
It is a lyophilized formulation comprising of all the inactive ingredients as in heat stable rotavirus vaccine without any rotavirus
Other Name: Placebo

Experimental: Heat Stable Rotavirus Vaccine
25 healthy infants who will be administered 3-doses of test HSRV vaccine spaced at 4-week intervals
Biological: Heat Stable Rotavirus (HSRV) Vaccine
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
Other Name: HSRV

Active Comparator: RotaTeq
25 healthy infants who will be administered 3-doses of comparator Rotateq® vaccine spaced at 4-week intervals
Biological: RotaTeq®
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.
Other Name: Active Comparator




Primary Outcome Measures :
  1. Any adverse event in adult cohort [ Time Frame: Up to two weeks after single dose of vaccine or placebo ]
  2. Serious adverse events in adult cohort [ Time Frame: Up to two weeks after single dose of vaccine or placebo ]
  3. Any adverse event in infant cohort [ Time Frame: Up to one month after 3 doses of vaccine or active control ]
  4. Serious adverse events in infant cohort [ Time Frame: Up to one month after 3 doses of vaccine or active control ]

Secondary Outcome Measures :
  1. Anti-Rotavirus IgA sero-response rate in infant cohort [ Time Frame: One month after third dose of vaccine or active control ]
    Serum IgA response rates, defined as the proportion of subjects with positive three-fold sero-response (i.e. a threefold rise in serum IgA anti-rotavirus antibody titres from baseline) 28 days after administration of third dose of investigational and comparator vaccine.

  2. Viral shedding after single dose of vaccine or placebo in adults [ Time Frame: Up to 7 days after single dose of vaccine or placebo ]
  3. Viral shedding in infants after each dose of vaccine or active control in infants [ Time Frame: Up to 7 days after each dose of vaccine ]


Information from the National Library of Medicine

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Ages Eligible for Study:   6 Weeks to 45 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Healthy Adults:

  1. Healthy adult subjects of either sex, between 18 to 45 years of age;
  2. No apparent signs or symptoms of ill health;
  3. 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;
  4. Subjects' availability for the entire period of the study and reachability by study staff for post vaccination follow-up.

Healthy Infants:

  1. Healthy infants of either sex, 6-8 weeks of age at the time of enrollment;
  2. Born after a gestational period of 36-42 weeks with birth weight ≥ 2kg;
  3. 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;
  4. Infant/Parents' or guardian's availability for the entire period of the study and reachability by study staff for post-vaccination follow-up.

Exclusion Criteria:

Healthy adults:

  1. Known or suspected impairment of immunological function; and known immunosuppressed family members/household contacts
  2. Known hypersensitivity to any component of the rotavirus vaccine;
  3. Fever, with axillary temperature ≥38.1 oC (≥100.5 oF) as measured by study staff;
  4. History of chronic diarrhea;
  5. Clinical evidence of active gastrointestinal illness;
  6. Receipt of any IM, oral, or IV corticosteroid treatment in the past 30 days;
  7. Subjects' suspected to be HIV, HBV or HCV positive from the available clinical history;
  8. Any subject who cannot be adequately followed for safety assessment;
  9. Any conditions which, in the opinion of the investigator, might interfere with the evaluation of the study objectives;
  10. Subject's inability to maintain diary card;
  11. Participation in another clinical trial investigating a vaccine, drug, medical device or medicinal procedure in the 4 weeks preceding the current vaccination trial;
  12. Planned participation in another clinical trial during the present trial period;
  13. 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:

  1. History of congenital abdominal disorders, intussusception, or abdominal surgery;
  2. Infants exhibiting signs of severe malnutrition or Known or suspected impairment of immunological function(s) in subject or his/her immediate family;
  3. Developmental delay or neurological disorder;
  4. Known hypersensitivity to any component of the rotavirus vaccine;
  5. Prior receipt of any rotavirus vaccine;
  6. Prior receipt of any dose of Diphtheria, Tetanus, Pertussis, Hepatitis B, Hib or polio virus containing vaccine(s). Birth dose of Hepatitis B and Oral Polio Vaccine is allowed to be administered to the infants as per the local immunization practices. Oral Polio Vaccines administered as a part of the National Pulse Polio Program are allowed to be administered to the infants.
  7. Fever, with axillary temperature ≥38.1 oC (≥100.5 oF) as measured by study staff.
  8. History of known rotavirus disease, chronic diarrhea, or failure to thrive;
  9. Clinical evidence of active gastrointestinal illness including ongoing diarrheal episode (infants with GERD can participate in the study so long as this condition is well controlled with or without medication);
  10. Receipt of any IM, oral, or IV corticosteroid treatment in the past 30 days (infants on inhaled steroids may be permitted to participate in the study);
  11. Infants residing in a household with an immuno-compromised person (e.g., individuals with a congenital immunodeficiency, HIV infection, leukemia, lymphoma, Hodgkin's disease, multiple myeloma, generalized malignancy, chronic renal failure, nephritic syndrome, organ or bone marrow transplantation, or those receiving immunosuppressive chemotherapy including long-term systemic corticosteroids);
  12. Infants already laboratory-confirmed or suspected to be HIV, HBV or HCV positive from the available clinical history or born to mothers known to be HIV, HBV or HCV positive (no specific screening for the purpose of the study would be carried out);
  13. Prior receipt of a blood transfusion or blood products, including immunoglobulins, in the past 4 weeks which might interfere with the assessment of the immune response;
  14. Any infants who cannot be adequately followed for safety assessment by a home visit;
  15. Any conditions which, in the opinion of the investigator, might interfere with the evaluation of the study objectives;
  16. Parent/s or guardian of infant unable to maintain symptom diary;
  17. Participation in another clinical trial investigating a vaccine, drug, medical device or medicinal procedure in the 4 weeks preceding the current vaccination trial;
  18. Planned participation in another clinical trial during the present trial period;
  19. Parents/ Guardians/ Legally Authorized Representatives 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.

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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02728869


Locations
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Bangladesh
Icddr,B
Dhaka, Bangladesh, 1212
Sponsors and Collaborators
MSD Wellcome Trust Hilleman Laboratories Pvt. Ltd.
Parexel
Investigators
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Principal Investigator: K Zaman, MBBS, PhD International Center for Diarrheal Disease Research, Bangladesh
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: MSD Wellcome Trust Hilleman Laboratories Pvt. Ltd.
ClinicalTrials.gov Identifier: NCT02728869    
Other Study ID Numbers: HL/RVV/CT1/15
First Posted: April 5, 2016    Key Record Dates
Last Update Posted: August 21, 2017
Last Verified: August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: Will disclose de-identified data of all subject after completion of study
Additional relevant MeSH terms:
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Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Vaccines
Immunologic Factors
Physiological Effects of Drugs