HIV-BIS: HIV-1 Peptide Immunisation of Individuals in West Africa to Prevent Disease

• Sponsor: Statens Serum Institut (Other)
• Overall Status: Completed
• CT.gov ID: NCT01141205
• Collaborator: Ministry of the Interior and Health, Denmark (Other), European and Developing Countries Clinical Trials Partnership (EDCTP) (Other)
• Enrollment: 18
• Location: 1
• Arms: 2
• Duration (Months): 34
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

Treatment: Immunization with peptide-mix and adjuvant. The vaccine should induce cellular immunity against HIV-1.

Target group: Untreated healthy individuals with chronic HIV-1 infection.

Purpose: The primary purpose is to evaluate tolerability and safety of the vaccine.

The secondary purpose is to evaluate the clinical effect of the vaccination treatment as measured by induction of immunity, lowering of viral load, induction of escape mutations in the virus and improvement in the patient CD4 lymphocyte blood counts.

The third purpose is to evaluate the feasibility of conducting a therapeutic HIV immunization study in a poorly-resourced African setting.

Design: The experiment is designed as a blinded, placebo-controlled phase 1 clinical trial in HIV-1 infected individuals in West Africa.

Numbers of individuals: Phase I: 20 fully evaluable HIV-1-infected patients should enter the study (15 vaccine treated and 5 placebo(saline) treated controls).

Condition or Disease	Intervention/Treatment	Phase
Aids, Cdc Group I	Biological: AFO-18; Drug: Saline	Phase 1

Detailed Description

The HIV infection does not leave lifelong immunity, but leads to break down of the immune system, opportunistic infections and death. The immunity obtained by the infection itself can only partially contain the HIV infection. The purpose with a targeted therapeutic vaccination is therefore in addition to the existing immunity to induce a broader, more powerful and more rationally or better directed immunity than the one induced by the "natural" HIV-1 infection. This would potentially lower the viral load in the blood making it more difficult to spread the virus to others and prolong the time to AIDS disease and medical treatment. There is a need for new rational vaccination possibilities, able to prevent (HIV) disease, postpone the need for antiretroviral medical treatment, prolong the life, and limit spread of HIV-1 in the population. The present protocol seak to introduce such a new immune treatment principle for HIV-1 infected individuals. In this study, individuals with chronic HIV-1 infection will be vaccinated with selected synthetic HIV immune-peptides representing new discovered conserved target´s on the virus. The vaccine should induce new immunity against several epitope targets on their HIV, whereby the HIV infection may be controlled for a longer time by the immune system. The purpose of the study is primarily to evaluate the safety and tolerability of the vaccine and secondary to evaluate the immunological and antiviral response in the vaccinated individuals.

Study Design

• Study Type: Interventional
• Actual Enrollment: 18 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: Phase I Study: HIV-1 Peptide Immunisation of Individuals in West Africa to Prevent Disease
• Study Start Date: Aug 1, 2009
• Actual Primary Completion Date: Jun 1, 2012
• Actual Study Completion Date: Jun 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AFO-18 18 peptides representing CD8 and CD4 epitopes mainly on HIV-1 in an adjuvants (CAF01)	Biological: AFO-18; 18 peptides representing CD8 and CD4 epitopes mainly on HIV-1 in an adjuvants (CAF01); Other Names: CAF01 HIV-1 peptides
Placebo Comparator: Saline Saline	Drug: Saline; 1.2 ml saline intramuscularly; Other Names: NaCl

Outcome Measures

Primary Outcome Measures

1. Tolerability and Safety of the Treatment. [up to 6 months after end of treatment]

   We report here the numbers of participants with vaccine related adverse events degree 3 or 4. Our goal for safety and tolerability was: "Fewer than or 3 patients of the 15 vaccine treated show treatment related (reaction 3) side-effects of degree 3 or 4".

Secondary Outcome Measures

1. Induction of New T-cell Immune Response by the Vaccine [up to 6 months after last immunisation]

   induction of new T-cell immune response against one or more of the vaccine epitopes using Interferon gamma Enzyme Linked Immuno spot assay (IFNg-ELISPOT assay)measuring Spot forming Unis per 1 million periferal blood mononuclear cells (SFU/1 mio PBMCs) above treshold (> 50 sfu/mio PBMC).

2. Lowering of HIV-1 RNA Viral-load in HIV-1 Immune Responders More Than 1 Log [up to 6 months post immunization]

   changes (lowering) in Plasma HIV-1 RNA viral-load (measured by Quantitative RT-PCR kit, ROCHE) of more than 1 log

3. Increase in Blood CD4 T-cell Counts [up to 6 months post vaccination]

   Analyzed: Participants (minus drop-outs and withdrawn) with measured blood CD4 T-cell counts (cells/microliter). Reported: Numbers of participants obtaining an increase in measured blood CD4 T-cell counts post vaccination of >100 CD4 Tcell per microliter

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. HIV-1 seropositive with measurable viral load >10e3 copies/ml and CD4+ T-cell count

400 CD4+ cells/µl.

1. Not in Antiretroviral Therapy (>1 year).

2. Male or female with age between 18 and 50 years.

3. Normal values for the area of liver and kidney enzymes, blood cell count with differential counts (e.g. white blood cells, lymphocytes, platelets/thrombocytes) and Hemoglobin

4. Expected to follow the instructions.

5. Written informed consent after oral and written information.

Exclusion Criteria:

1. Vaccinated with other vaccines within 3 months before the first vaccination.

2. Treated with immune modulating medicine within 3 month before the first immunization.

3. Other important active chronic infectious diseases likely to influence the HIV-1 infection, like HIV-2, HBV, HCV and TB

4. Significant medical disease as judged by the investigators, for example severe asthma/COLD, badly regulated heart disease, insulin-dependent diabetes mellitus.

5. Severe allergy or earlier anaphylactic reactions.

6. Active autoimmune diseases.

7. Simultaneous treatment with other experimental drugs.

8. Laboratory parameters outside the 'normal' range for the area and which are considered clinically significant.

9. Pregnancy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital Nacional Simao Mendes	Bissau		Guinea-Bissau

Sponsors and Collaborators

• Statens Serum Institut
• Ministry of the Interior and Health, Denmark
• European and Developing Countries Clinical Trials Partnership (EDCTP)

Investigators

• Study Director: Anders Fomsgaard, DMSc, Statens Serum Institut
• Principal Investigator: Zacarias Jose da Silva, PhD, Bandim Health Project, Bissau, Guinea-Bissau

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Anders Fomsgaard, Chief Medical Doctor, Statens Serum Institut
• ClinicalTrials.gov Identifier: NCT01141205
• Other Study ID Numbers: HIV-BIS NCP03/2009; EDCTP_MSI.2009.10800.001
• First Posted: Jun 10, 2010
• Last Update Posted: Aug 8, 2013
• Last Verified: Aug 1, 2013

• Keywords provided by Anders Fomsgaard, Chief Medical Doctor, Statens Serum Institut: AIDS vaccines; HIV-1 vaccine; Therapeutic vaccine; Cellular immunity

Study Results

Participant Flow

Recruitment Details	medical clinic

Arm/Group Title	AFO-18	Saline
Arm/Group Description	18 peptides representing 15 CD8 and 3 CD4 epitopes on HIV-1 plus 1 CD4 T helper epitope unrelated to HIV in an adjuvant (CAF01). Total 4.5 mg peptide (250 micro gram of each peptide) in CAF01 adjuvant. Total volume of 1.25 ml was injected i.m. (in m. deltoideus) at weeks 0, 2, 4, 8	Placebo was Sterile saline injection, 1.25 ml i.m. (in m. deltoideus) at each vaccination weeks 0, 2, 4, 8
Period Title: Overall Study
STARTED	18	5
COMPLETED	15	3
NOT COMPLETED	3	2

Baseline Characteristics

Arm/Group Title	AFO-18	Saline	Total
Arm/Group Description	18 peptides representing CD8 and CD4 epitopes mainly on HIV-1 in an adjuvants (CAF01)	Saline injection	Total of all reporting groups
Overall Participants	18	5	23
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	18 100%	5 100%	23 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	34 (2)	29 (2)	32 (2)
Sex: Female, Male (Count of Participants)
Female	17 94.4%	3 60%	20 87%
Male	1 5.6%	2 40%	3 13%
Region of Enrollment (participants) [Number]
Guinea-Bissau	18 100%	5 100%	23 100%

Outcome Measures

1. Primary Outcome

Title	Tolerability and Safety of the Treatment.
Description	We report here the numbers of participants with vaccine related adverse events degree 3 or 4. Our goal for safety and tolerability was: "Fewer than or 3 patients of the 15 vaccine treated show treatment related (reaction 3) side-effects of degree 3 or 4".
Time Frame	up to 6 months after end of treatment

Outcome Measure Data

Analysis Population Description

Analyzed: number of participants started minus individuals lost to follow up or participants that withdraw. Thus we include the two individuals where the physician stopped his/her participation because of SAE not related to the vaccine or to the placebo. Reported: numbers of participants with vaccina related SAE

Arm/Group Title	Vaccinee	Placebo
Arm/Group Description	participants receiving active peptide in CAF01 adjuvants vaccine	participants receiving saline
Measure Participants	16	4
Number [participants]	0 0%	0 0%

2. Secondary Outcome

Title	Induction of New T-cell Immune Response by the Vaccine
Description	induction of new T-cell immune response against one or more of the vaccine epitopes using Interferon gamma Enzyme Linked Immuno spot assay (IFNg-ELISPOT assay)measuring Spot forming Unis per 1 million periferal blood mononuclear cells (SFU/1 mio PBMCs) above treshold (> 50 sfu/mio PBMC).
Time Frame	up to 6 months after last immunisation

Outcome Measure Data

Analysis Population Description

Analyzed: Participants minus drop-outs and withdrawn participants. Reported: numbers of participants with a new induced ELISPOT Y-cell immune response to the vaccine peptide epitopes

Arm/Group Title	AFO-18	Placebo Saline
Arm/Group Description	18 peptides representing CD8 and CD4 epitopes mainly on HIV-1 in an adjuvants (CAF01)	Saline injection
Measure Participants	14	2
Number [ELISPOT responders]	6	0

3. Secondary Outcome

Title	Lowering of HIV-1 RNA Viral-load in HIV-1 Immune Responders More Than 1 Log
Description	changes (lowering) in Plasma HIV-1 RNA viral-load (measured by Quantitative RT-PCR kit, ROCHE) of more than 1 log
Time Frame	up to 6 months post immunization

Outcome Measure Data

Analysis Population Description

Participants minus drop outs and participants withdrawn by them selves or by the physicians

Arm/Group Title	Vaccinee	Saline
Arm/Group Description	participants receiving active HIV-1 peptide vaccine in CAF01 adjuvant i.m.	Placebo participants receiving sterile saline i.m.
Measure Participants	15	3
Number [participants with lowering of VL]	0 0%	0 0%

4. Secondary Outcome

Title	Increase in Blood CD4 T-cell Counts
Description	Analyzed: Participants (minus drop-outs and withdrawn) with measured blood CD4 T-cell counts (cells/microliter). Reported: Numbers of participants obtaining an increase in measured blood CD4 T-cell counts post vaccination of >100 CD4 Tcell per microliter
Time Frame	up to 6 months post vaccination

Outcome Measure Data

Analysis Population Description

Participants minus drop-outs and withdrawn participants

Arm/Group Title	Vaccinee	Placebo
Arm/Group Description	participants receiving active peptide in CAF01 adjuvants vaccine	participants receiving saline
Measure Participants	15	3
Number [participants with increased CD4 count]	0 0%	0 0%

Adverse Events

Time Frame	6 months
Adverse Event Reporting Description	One participant in the vaccinee group of 18 individuals had a SAE (serious infection) not related to the vaccine. One participant in the saline placebo group of 5 individuals experienced a SAE (increase in liver enzymes) not related to the placebo saline. None others experienced any AE was noted.
Arm/Group Title	AFO-18		Saline
Arm/Group Description	18 peptides representing CD8 and CD4 epitopes mainly on HIV-1 in an adjuvants (CAF01)		Saline injection
All Cause Mortality
	AFO-18		Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	AFO-18		Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/18 (5.6%)		1/5 (20%)
Infections and infestations
Died of pneumonia	1/18 (5.6%)	1	0/5 (0%)	0
Increase in liver enzymes	0/18 (0%)	0	1/5 (20%)	1
Other (Not Including Serious) Adverse Events
	AFO-18		Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/18 (0%)		0/5 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.