A Phase IIA Trial to Evaluate the Safety and Immunogenicity of a DNA HIV-1 Vaccine Followed by an MVA HIV-1 Vaccine in HIV-uninfected Volunteers

International AIDS Vaccine Initiative

Status and phase: Completed; Phase 2

Conditions: HIV Infections

Treatments: Biological: DNA.HIVA; Biological: MVA.HIVA

Study type: Interventional

Funder types: Other; NETWORK

Identifiers

NCT01371175

IAVI 010

Details and patient eligibility

About

The purpose of this study is to evaluate the safety and tolerability of plasmid DNA and recombinant MVA (Modified Vaccinia Virus Ankara) in a prime-boost regimen.

Approximately 111 volunteers (90 vaccine recipients/21 placebo recipients) will be enrolled at two sites. Approximately 56 volunteers will be enrolled at each site. An over-enrolment of up to 10% (approximately 10 additional volunteers) will be permitted in the study.

Enrollment: 115 patients

Sex: All

Ages: 18 to 60 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

1. Healthy males and females;
2. Age at least 18 years on the day of screening and no greater than 60 years on the day of enrolment;
3. Available for follow up for the planned duration of the study (screening plus 18 months);
4. Able to give written informed consent;
5. Does not engage in risk behaviour as defined by the protocol, willing to undergo HIV testing and receive results;
6. If sexually active female, using an effective method of contraception (combined oral contraceptive pill; injectable contraceptive; IUCD; condoms; anatomical sterility in self or partner) from screening until at least 4 months after last vaccination and willing to undergo urine pregnancy tests at screening and prior to each vaccination and 4 months after the last vaccination;
7. If sexually active male, willing to use an effective method of contraception (such as condoms) from screening until 4 months after the last vaccination.

Exclusion Criteria:

1. Clinically relevant abnormality on history or examination including history of immunodeficiency or use of systemic corticosteroids, immunosuppressive, antiviral, anticancer, or other medications considered significant by the designated trial physician in last 6 months;
2. Presence of any chronic condition;
3. Any of the following abnormal laboratory parameters that are moderate, severe, or very severe: haematology (haemoglobin, absolute neutrophil count absolute lymphocyte count , absolute CD4 count, platelets); urinalysis, biochemistries (total bilirubin, creatinine, AST, ALT). Volunteers with mild laboratory abnormalities which are judged by the principal investigator or designee to be not clinically significant may be enrolled.
4. If female, pregnant or planning a pregnancy within 4 months after last vaccination or lactating;
5. Receipt of live attenuated vaccine within 60 days or other vaccine within 14 days of enrolment;
6. Receipt of blood transfusion or blood products 6 months prior to enrolment;
7. Participation in another clinical trial of an investigational product currently or within last 12 weeks or expected participation during this study;
8. History of severe local or general reaction to vaccination or history of allergic reactions;
9. History of grand-mal epilepsy, or currently taking anti-epileptics;
10. Confirmed HIV-1 or HIV-2 seropositive;
11. Positive for hepatitis B (surface antigen) or confirmed diagnosis of active syphilis at the time of enrolment (RPR positive and TPHA positive or equivalent), positive for hepatitis C antibodies;
12. Unlikely to comply with protocol. Prior receipt of smallpox vaccination should be documented, but will not be an exclusion criterion.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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115 participants in 9 patient groups

Group A

Experimental group

Description:

DNA or Placebo delivered intramuscularly at Months 0 and 1 followed by MVA or Placebo at Months 5 and 8 delivered subcutaneously. Vaccine:Placebo =12/3

Treatment:

Biological: MVA.HIVA

Biological: MVA.HIVA

Biological: DNA.HIVA

Biological: MVA.HIVA

Group B

Experimental group

Description:

DNA or Placebo delivered intramuscularly at Months 0 and 1 followed by MVA or Placebo at Months 5 and 8 delivered intramuscularly. Vaccine:Placebo =12/3

Treatment:

Biological: MVA.HIVA

Biological: MVA.HIVA

Biological: DNA.HIVA

Biological: MVA.HIVA

Group C

Experimental group

Description:

DNA or Placebo delivered intramuscularly at Months 0 and 1 followed by MVA or Placebo at Months 5 and 8 delivered intradermally. Vaccine:Placebo =18/3

Treatment:

Biological: MVA.HIVA

Biological: MVA.HIVA

Biological: DNA.HIVA

Biological: MVA.HIVA

Group D

Experimental group

Description:

DNA or Placebo delivered intramuscularly at Months 0 and 1 followed by MVA or Placebo at Months 5 and 8 delivered subcutaneously. Vaccine:Placebo =12/3

Treatment:

Biological: MVA.HIVA

Biological: MVA.HIVA

Biological: DNA.HIVA

Biological: MVA.HIVA

Group E

Experimental group

Description:

DNA or Placebo delivered intramuscularly at Months 0 and 1 followed by MVA or Placebo at Months 5 and 8 delivered intramuscularly. Vaccine:Placebo =12/3

Treatment:

Biological: MVA.HIVA

Biological: MVA.HIVA

Biological: DNA.HIVA

Biological: MVA.HIVA

Group F

Experimental group

Description:

DNA or Placebo delivered intramuscularly at Months 0 and 1 followed by MVA or Placebo at Months 5 and 8 delivered subcutaneously. Vaccine:Placebo =12/3

Treatment:

Biological: MVA.HIVA

Biological: MVA.HIVA

Biological: DNA.HIVA

Biological: MVA.HIVA

Group G

Experimental group

Description:

DNA or Placebo delivered intramuscularly at Months 0 and 1 followed by MVA or Placebo at Months 5 and 8 delivered intramuscularly. Vaccine:Placebo =12/3

Treatment:

Biological: DNA.HIVA

Groups C2/D2/E2 (Subgroups of C,D,E)

Experimental group

Description:

DNA or Placebo delivered intramuscularly at Months 0 and 1 followed by MVA or Placebo at Months 5 and Month 12+ (volunteers offered second MVA/placebo more than 12 months (late boost) after their enrollment into their original treatment assignment) delivered ID, SC, or IM according to original randomization. Vaccine:Placebo = blinded ratio, maximum in C2/D2/E2 = 16.

Treatment:

Biological: MVA.HIVA

Biological: MVA.HIVA

Biological: DNA.HIVA

Biological: MVA.HIVA

Group F2/G2 (Subgroup of F and G)

Experimental group

Description:

DNA or Placebo delivered intramuscularly at Months 0 and 1 followed by MVA or Placebo at Months 5 and Month 12+ (volunteers offered second MVA/placebo more than 12 months (late boost) after their enrollment into their original treatment assignment) delivered either SC or IM according to original randomization. Vaccine:Placebo = blinded ratio, maximum in F/G= 29.

Treatment:

Biological: MVA.HIVA

Biological: MVA.HIVA

Biological: DNA.HIVA

Biological: MVA.HIVA