Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR201412000957310 Date of Approval: 03/12/2014
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title A phase Ib, open-label, clinical trial to evaluate the safety, tolerability and immunogenicity of the Ebola chimpanzee adenovirus vector vaccines, vrc-eboadc069-00-vp (Cad3-Ebo) and vrc-eboadc076-00-vp (Cad3-Eboz), in healthy adults in Kampala, Uganda
Official scientific title A phase Ib, open-label, clinical trial to evaluate the safety, tolerability and immunogenicity of the Ebola chimpanzee adenovirus vector vaccines, vrc-eboadc069-00-vp (Cad3-Ebo) and vrc-eboadc076-00-vp (Cad3-Eboz), in healthy adults in Kampala, Uganda
Brief summary describing the background and objectives of the trial This is an open-label study evaluating safety and immunogenicity. 90 healthy adults in the Kampala area ages 18-65 will be randomized. Study duration is 48 weeks. Group 1: Sixty Ebola vaccine naïve subjects will be randomized to receive a single injection of vaccine as follows: a) 15 subjects will receive cAd3-EBOZ (Zaire) at 1x1010 PU b) 15 subjects will receive cAd3-EBOZ (Zaire) at 1x1011 PU c) 15 subjects will receive cAd3-EBO (Zaire and Sudan) at 2x1010 PU d) 15 subjects will receive cAd3-EBO (Zaire and Sudan) at 2x1011 PU Group 2: Up to 30 eligible subjects who previously participated in the RV 247 vaccine clinical trial and received VRC-EBODNA023-00-VP (Ebola DNA WT) or in combination with VRC-MARDNA025-00-VP (Marburg DNA) will be randomized to receive a single injection of vaccine as follows: a) 15 subjects will receive cAd3-EBO (Zaire and Sudan) at 2x1010 PU b) 15 subjects will receive cAd3-EBO (Zaire and Sudan) at 2x1011 PU Intervention VRC-EBOADC069-00-VP (cAd3-EBO) is composed of two recombinant cAd3 vectors in a 1:1 ratio that express Ebola WT GPs from Zaire and Sudan strains. It is formulated at 2 x 1011 PU/mL. VRC-EBOADC076-00-VP [cAd3-EBOZ] is composed one vector that expresses Ebola WT GP from the Zaire strain. It is formulated at 1 x 1011 PU/mL Study Objectives Primary Objectives ¿ To evaluate the safety and tolerability of VRC-EBOADC076-00-VP when administered IM at doses of 1 x 1010 particle units (PU) and 1 x 1011 particle units (PU) to healthy adults 18-65; ¿ To evaluate the safety and tolerability of VRC-EBOADC069-00-VP when administered IM at doses of 2 x 1010 particle units (PU) and 2 x 1011 particle units (PU) to healthy adults 18-65.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) RV 422
Disease(s) or condition(s) being studied Ebola Hemorrhagic Fever,Infections and Infestations
Sub-Disease(s) or condition(s) being studied Ebola
Purpose of the trial Prevention
Anticipated trial start date 05/01/2015
Actual trial start date
Anticipated date of last follow up 31/03/2016
Actual Last follow-up date
Anticipated target sample size (number of participants) 90
Actual target sample size (number of participants)
Recruitment status Not yet recruiting
Publication URL Pending
Secondary Ids Issuing authority/Trial register
Pending Uganda National Council of Science & Technology
WRAIR#2170 Human Subjects Protection Branch, Walter Reed Army Institute of Research
MUSPH#247 Makarere Univeristy School of Public Health
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Simple randomisation using a radomisation table created by a computer software program. A total of 90 subjects will be enrolled to receive one of two vaccines with 30 subjects receiving the cAd3-EBOZ and 60 subjects receiving cAd3-EBO. Enrollment to the latter is further stratified on Ebola vaccination history with Ebola vaccine naive subjects randomized 1:1:1:1 to Groups 1a, 1b, 1c and 1d and subjects with a prior Ebola vaccination randomized 1:1 between Groups 2a and 2b. NA. This is an open label Clinical Trial Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group cAd3-EBOZ 1x10 to power 10 PU IM Single injection VRC-EBOADC076-00-VP [cAd3-EBOZ] is composed one vector that expresses Ebola WT GP from the Zaire strain 15
Experimental Group cAd3-EBOZ 1x10 to the power 11 PU IM Single injection VRC-EBOADC076-00-VP [cAd3-EBOZ] is composed one vector that expresses Ebola WT GP from the Zaire strain 15
Experimental Group cAd3-EBO 2x10 to the power 10 PU IM Single injection VRC-EBOADC069-00-VP (cAd3-EBO) is composed of two recombinant cAd3 vectors in a 1:1 ratio that express Ebola WT GPs from Zaire and Sudan strains 15
Experimental Group cAd3-EBO cAd3-EBO at 2x10 to the power 11 PU IM Single injection VRC-EBOADC069-00-VP (cAd3-EBO) is composed of two recombinant cAd3 vectors in a 1:1 ratio that express Ebola WT GPs from Zaire and Sudan strains 15
Experimental Group cAd3-EBO for GROUP II 2x10 to the power 10 PU IM Single injection VRC-EBOADC069-00-VP (cAd3-EBO) is composed of two recombinant cAd3 vectors in a 1:1 ratio that express Ebola WT GPs from Zaire and Sudan strains 15
Experimental Group cAd3-EBO for GROUP II 2 x 10 to the power 11 PU, IM Single injection VRC-EBOADC069-00-VP (cAd3-EBO) is composed of two recombinant cAd3 vectors in a 1:1 ratio that express Ebola WT GPs from Zaire and Sudan strains 15
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1. 18 to 65 years old. 2. Available for clinical follow-up through Week 48 after enrollment. 3. Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process. 4. Must be willing to be taken home at enrollment visit and allow home visits if participant does not keep appointments 5. Must complete an Assessment of Understanding (AoU) prior to enrollment by answering 9 out of 10 questions at least once in 3 attempts. 6. Able to read (English or Luganda) and willing to complete the informed consent process. 7. Willing to donate blood for sample storage to be used for future research. 8. In good general health without clinically significant medical history. 9. Physical examination and laboratory results without clinically significant findings and a body mass index (BMI) ¿ 40 within the 56 days prior to enrollment. Laboratory Criteria within 56 days prior to enrollment: 10. Hemoglobin ¿ 11.0 g/dL for women; ¿12.5 g/dL for men. 11. White blood cells (WBC) = 2,500-12,000 cells/mm3. 12. WBC differential either within institutional normal range or accompanied by the Principal Investigator (PI) or designee approval. 13. Total lymphocyte count ¿ 800 cells/mm3. 14. Platelets = 125,000 ¿ 400,000/mm3. 15. Alanine aminotransferase (ALT) ¿ 1.25 x upper limit of normal. 16. Serum creatinine ¿ 1 x upper limit of normal. 17. Partial thromboplastin time (PTT) within institutional normal range. 18. Prothrombin time (PT) within institutional normal range. 19. HIV-uninfected as evidenced by a negative FDA-approved HIV diagnostic test. Female-Specific Criteria: 20. Negative ¿-HCG (human chorionic gonadotropin) pregnancy test (urine or serum) on day of enrollment if woman is presumed to be of reproductive potential. 21. Agrees to use an effective means of birth control from at least 21 days prior to enrollment through 24 weeks after study vaccination if presumed to be of reproductive potential. 1.Investigational Ebola or Marburg vaccine (other than the Ebola DNA vaccine delivered in RV 247) in a prior clinical trial or prior receipt of a cAd3 adenoviral vectored investigational vaccine. 2. Chronic use of immunomodulators and systemic glucocorticoids in daily doses of glucocorticoid equivalence > 20 mg of prednisolone, for periods exceeding 10 days. Non-steroidal anti-inflammatory drugs [NSAIDS] are permitted. Participants that have used less than the stated glucocorticoid dose may still be excluded at the Investigator¿s discretion. 3. Blood products within 112 days (16 weeks) prior to enrollment. 4. Investigational research agents within 28 days (4 weeks) prior to enrollment. 5. Live attenuated vaccines within 28 days (4 weeks) prior to enrollment. 6. Subunit or killed vaccines within 14 days (2 weeks) prior to enrollment. 7. Current anti-tuberculosis prophylaxis or therapy. Female-specific criteria: 8. Woman who is breast-feeding or planning to become pregnant during the first 24 weeks after study vaccine administration. Volunteer has a history of any of the following clinically significant conditions: 9. Serious adverse reactions to vaccines such as anaphylaxis, urticaria (hives), respiratory difficulty, angioedema, or abdominal pain. 10. Clinically significant autoimmune disease or immunodeficiency. 11. Asthma that is not well controlled. 12. Diabetes mellitus (type I or II), with the exception of gestational diabetes. 13. Thyroid disease that is not well controlled. 14. A history of hereditary angioedema (HAE), acquired angioedema (AAE), or idiopathic forms of angioedema. 15. Idiopathic urticaria within the last 1 year. 16. Hypertension that is not well controlled. 17. Bleeding disorder diagnosed by a doctor (e.g. factor deficiency, coagulopathy, or platelet disorder requiring special precautions) or significant bruising or bleeding difficulties with IM injections or blood draws. 18. Malignancy that is active or history of a malignancy that is likely 18 Year(s) 65 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 27/11/2014 Makerere University School of Public Health REC
Ethics Committee Address
Street address City Postal code Country
Mulago Hospital Complex Kampala 7072 Uganda
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Safety At Day 3 and Weeks 1, 2, 4, 8, 16, 24 and 48
Secondary Outcome Immunogenicity Weeks 1, 2, 4, 8, 16, 24 and 48
Secondary Outcome Explorative Weeks 1, 2, 4, 8, 16, 24 and 48
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Makerere University Walter Reed Project Plot 42 Nakasero Road, Nakasero Hill Kampala 16524 Uganda
FUNDING SOURCES
Name of source Street address City Postal code Country
US National Institute of Allergy and Infectious Diseases (NIAID) NIAID Office of Communications and Government Relations 5601 Fishers Lane, MSC 9806 Bethesda, MD 20892-9806 Rockville, MD 20852 NA United States of America
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor US National Institute of Allergy and Infectious Diseases (NIAID) NIAID Office of Communications and Government Relations 5601 Fishers Lane, MSC 9806 Bethesda, MD 20892-9806 Rockville, MD 20852 NA United States of America Funding Agency
COLLABORATORS
Name Street address City Postal code Country
Vaccine Research Center, NIAID, NIH Vaccine Evaluation Clinic (5th Floor, NE-S), NIH Complex, Wisconsin Avenue Bethesda NA United States of America
U.S. Military HIV Research Program 6720A Rockledge Drive Suite 400 Bethesda, MD 20817 Silver Spring, MD NA United States of America
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Hannah Kibuuka Hkibuuka@muwrp.org +256-312-330400 Plot 42 Nakasero Road
City Postal code Country Position/Affiliation
Kampala 16524 Uganda Director
Role Name Email Phone Street address
Public Enquiries Jauhara Nanyondo Jnanyondo@muwrp.org +256-312-330400 Plot 42 Nakasero Road
City Postal code Country Position/Affiliation
Kampala 16524 Uganda Community Outreach Coordinator
Role Name Email Phone Street address
Scientific Enquiries Allan Tindikahwa Atindikahwa@muwrp.org +256-312-330400 Plot 42 Nakasero Road
City Postal code Country Position/Affiliation
Kampala 16524 Uganda Pharmacist of Record
REPORTING
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