HIV InfectionsPhase 1NCT01123915
A Safety and Immunogenicity Study of 3 Doses of Opal Immunotherapy in HIV Infected People
A Phase 1 study testing Opal-HIV-Gag(c) Low Dose, Opal-HIV-Gag(c) Medium dose and Opal-HIV-Gag(c) High dose in people with HIV Infections, run by Medicines Development for Global Health at 1 site in United Kingdom.
Trial summary
This phase I study is the first step to determine if Opal immunotherapy may have potential utility as a treatment for HIV. Although effective treatments for HIV infection exist, they are limited by the requirement for life-long daily treatment, cost, side effects, and the development of resistance. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- HIV Infections
- What is being tested?
- Opal-HIV-Gag(c) Low Dose, Opal-HIV-Gag(c) Medium dose and Opal-HIV-Gag(c) High dose
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 22 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- May 2010to Dec 2011
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Provision of written informed consent
- Documented laboratory diagnosis of HIV 1 infection
- Documented HIV clade of infection
- 18 - 60 years of age, inclusive
- Stable antiretroviral therapy (ART) regimen containing at least 3 active ART agents for at least 2 months prior to Baseline
- Plasma HIV-Ribonucelc acid (RNA) <400 copies/millilitre (mL) for 6 months up to and including Screening. Subjects on stable ART with a single value ≥400 copies/mL (i.e. the result is unconfirmed by subsequent testing) within this timeframe may be included at the discretion of the Investigator
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- CD4+ T-cell count ≥350 cells/cubic millimetres (mm3) at Screening (with nadir ≥100 cells/mm3)
- A positive immunogenic response when stimulated with HIV-1 Gag clade C peptides at Screening
- Male or female. Women of child-bearing potential must be using two effective methods of contraception and agree to continue to do so from Screening, throughout study medication dosing and for 28 days after the last dose of study medication
Who cannot join
- Any serious or active medical or psychiatric illness which, in the opinion of the Investigator, would interfere with treatment, assessment, compliance with the protocol, or subject safety. This would include any active clinically significant renal, cardiac, pulmonary, vascular, or metabolic (thyroid disorders, adrenal disease) illness, or malignancy
- Hepatitis B virus surface antigen, or Hepatitis C virus (HCV) antibody and HCV-RNA positive at Screening
- Female subjects who are lactating and those of reproductive potential with a positive urine pregnancy test at either Screening or Baseline
- A new AIDS-defining condition diagnosed within 42 days prior to Baseline visit
- Known or suspected allergy to Dimethyl Sulfoxide
- History of allergy or reaction to medications (including peptide or protein containing agents) or history of severe allergy that, in the opinion of the Investigator, might compromise the subject's participation in any way
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- Moderate or severe asthma, defined as at least chronic moderate symptoms which frequently interfere with daily activities and require anti-asthma/anti-inflammatory agents
- Have received immunomodulating agents (including immunosuppressive agents, interferon or other immune or cytokine-based therapies), immunisation, and/or systemic chemotherapeutic agents within 60 days of Screening or expected to receive these agents during the course of the study
- Recipient of live attenuated vaccines within 60 days of Screening
- Recipient of whole killed, toxoid or sub-unit vaccines (e.g. influenza, pneumococcus, tetanus, hepatitis B) within 42 days prior to Baseline
- Ever received an HIV prophylactic or immunotherapeutic vaccine (does not apply to subjects who have written documentation of receiving placebo or adjuvant only)
- Recreational and/or therapeutic drug or alcohol use that, in the opinion of the Investigator, might compromise the subject's participation in any way.
- Medical or psychiatric condition or occupational responsibilities that may preclude compliance with the protocol
- Laboratory blood values:
- Haemoglobin <11.0 grams/decilitre (g/dL) for men and <10.0 g/dL for women
- Neutrophil count <800/mm3
- Platelet count <50,000/mm3
- Aspartate aminotransferase or Alanine transaminase >2.5 times Upper Limit of Normal (ULN)
- Lipase >2.5 times ULN
- Amylase >1.5 times ULN (unless serum lipase is ≤1.5 times ULN)
- Subjects with an estimated creatinine clearance of <80 mL/minute
- Recipients of blood products or immunoglobulins within 6 months prior to Screening or loss of 450 mL or more of blood during the three months prior to Screening
- Recipients of experimental or investigational agents within 30 days prior to Screening
- Previous participation in this study
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
St Stephen's Centre, Chelsea and Westminster Foundation Trust
London, SW10 9NH
About this study
Official title: A Phase 1, Dose Escalating, Single Centre, Double Blind Study of the Safety and Immunogenicity of Opal-HIV-Gag Clade C in HIV Positive Subjects
This phase I study is the first step to determine if Opal immunotherapy may have potential utility as a treatment for HIV. Although effective treatments for HIV infection exist, they are limited by the requirement for life-long daily treatment, cost, side effects, and the development of resistance.
There is a need for therapeutic approaches that induce or enhance T-cell immunity to control HIV disease. Overlapping Peptide-pulsed Autologous Cells (Opal) is a technique where autologous peripheral blood mononuclear cells (PBMC) or whole blood is pulsed with sets of overlapping peptides spanning whole proteins of HIV.
Read the detailed description
Opal-HIV-Gag(c) is not for direct injection and is administered by ex vivo incubation of whole blood or separated blood components (such as white blood cells or peripheral blood mononuclear cells) and reinfusion.
As a practical alternative to PBMC separation and to optimise vaccine presentation during the ex vivo incubation, a blood cell separation device will be used to separate the whole blood and enrich the white blood cell component. The device processes whole blood in a closed, single use disposable kit. Reconstituted Opal-HIV-Gag(c)or matching placebo will be added to the white blood cells, incubated for one hour and reinfused into the subject. Subjects will receive 4 administrations at 4 weekly intervals. Subjects are followed for 12 weeks after the final administration.
Each dose group will be enrolled sequentially, with a sentinel group for each dose group. Satisfactory safety data from each cohort, reviewed by a Data Safety Monitoring Board, will permit dose escalation.
- Conditions
- HIV Infections
- Being tested
- Opal-HIV-Gag(c) Low Dose, Opal-HIV-Gag(c) Medium dose, Opal-HIV-Gag(c) High dose, Dimethyl Sulfoxide
- Keywords
- HIV, Therapeutic, Immunotherapy, Acquired Immunodeficiency Syndrome, Virus Diseases, Lentivirus Infections, Human Immunodeficiency Virus
- Medical subject headings
- HIV Infections, Acquired Immunodeficiency Syndrome, Virus Diseases, Lentivirus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Opal-HIV-Gag(c) Low DoseBiological
Opal-HIV-Gag(c) Medium doseBiological
Opal-HIV-Gag(c) High doseBiological
Dimethyl SulfoxideOther
| Study group | Role | What they receive |
|---|---|---|
| Opal-HIV-Gag(c) | Experimental | Opal-HIV-Gag(c) administered ex vivo to separated white blood cells on 4 occasions at 4 weekly intervals. Receives: Biological: Opal-HIV-Gag(c) Low Dose; Biological: Opal-HIV-Gag(c) Medium dose; Biological: Opal-HIV-Gag(c) High dose |
| Diluent | Placebo comparator | Administered ex vivo to separated white blood cells on 4 occasions at 4 weekly intervals. Receives: Other: Dimethyl Sulfoxide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety
Examined through treatment-emergent adverse events, vital signs and routine laboratory screening.
Measured: Several points throughout the 12 week active phase and 12 week and follow up period
Secondary outcomes (2)
Immunogenicity
Immunogenicity will be assessed by ELISpot and other markers of immune response
Measured: Several points throughout the 12 week active phase and 12 week and follow up period
Impact on HIV infection
Assessed by HIV-1 viral load and CD4 T-cell counts.
Measured: Several points throughout the 12 week active phase and 12 week and follow up period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 May 2010 (estimated)
- Study startMay 2010
- Primary completionDec 2011
- Study completionDec 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medicines Development for Global Health
- Sponsor type
- University, hospital or other
- Collaborators
- Phillip T. and Susan M. Ragon Foundation, Imperial College London
- Responsible party
- Sponsor
- Investigators
- Marta Boffito, MD PhD, Principal investigator, St Stephen's AIDS Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01123915
- Sponsor's protocol ID
- Opal-HIV-1001
- Other IDs
- 2008-005142-23, 2008
- Status last verified
- Nov 2011
- First submitted
- 13 May 2010
- Last updated
- 22 Mar 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Kloverpris HN, Jackson A, Handley A, Hayes P, Gilmour J, Riddell L, Chen F, Atkins M, Boffito M, Walker BD, Ackland J, Sullivan M, Goulder P. Non-immunogenicity of overlapping gag peptides pulsed on autologous cells after vaccination of HIV infected individuals. PLoS One. 2013 Oct 4;8(10):e74389. doi: 10.1371/journal.pone.0074389. eCollection 2013.
PubMed 24124451Jackson A, Kloverpris HN, Boffito M, Handley A, Atkins M, Hayes P, Gilmour J, Riddel L, Chen F, Bailey-Tippets M, Walker B, Ackland J, Sullivan M, Goulder P. A randomised, placebo-controlled, first-in-human study of a novel clade C therapeutic peptide vaccine administered ex vivo to autologous white blood cells in HIV infected individuals. PLoS One. 2013 Sep 17;8(9):e73765. doi: 10.1371/journal.pone.0073765. eCollection 2013.
PubMed 24069230
Study at a glance
From the registry record, last updated by the sponsor on 22 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Dose Escalating, Single Centre, Double Blind Study of the Safety and Immunogenicity of Opal-HIV-Gag Clade C in HIV Positive Subjects
- ClinicalTrials.gov ID
- NCT01123915
- Acronym / sponsor ID
- Opal-HIV-1001
- Conditions
- HIV Infections
- Keywords
- HIV, Therapeutic, Immunotherapy, Acquired Immunodeficiency Syndrome, Virus Diseases, Lentivirus Infections, Human Immunodeficiency Virus
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Medicines Development for Global HealthUniversity, hospital or other
- Collaborators
- Phillip T. and Susan M. Ragon Foundation, Imperial College London
- Study start
- May 2010
- Primary completion
- Dec 2011 (actual)
- Study completion
- Dec 2011 (actual)
- First posted
- 14 May 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase I study is the first step to determine if Opal immunotherapy may have potential utility as a treatment for HIV. Although effective treatments for HIV infection exist, they are limited by the requirement for life-long daily treatment, cost, side effects, and the development of resistance.
There is a need for therapeutic approaches that induce or enhance T-cell immunity to control HIV disease. Overlapping Peptide-pulsed Autologous Cells (Opal) is a technique where autologous peripheral blood mononuclear cells (PBMC) or whole blood is pulsed with sets of overlapping peptides spanning whole proteins of HIV.
Detailed description
Opal-HIV-Gag(c) is not for direct injection and is administered by ex vivo incubation of whole blood or separated blood components (such as white blood cells or peripheral blood mononuclear cells) and reinfusion.
As a practical alternative to PBMC separation and to optimise vaccine presentation during the ex vivo incubation, a blood cell separation device will be used to separate the whole blood and enrich the white blood cell component. The device processes whole blood in a closed, single use disposable kit. Reconstituted Opal-HIV-Gag(c)or matching placebo will be added to the white blood cells, incubated for one hour and reinfused into the subject. Subjects will receive 4 administrations at 4 weekly intervals. Subjects are followed for 12 weeks after the final administration.
Each dose group will be enrolled sequentially, with a sentinel group for each dose group. Satisfactory safety data from each cohort, reviewed by a Data Safety Monitoring Board, will permit dose escalation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Opal-HIV-Gag(c) | Experimental | Biological: Opal-HIV-Gag(c) Low Dose, Biological: Opal-HIV-Gag(c) Medium dose, Biological: Opal-HIV-Gag(c) High doseOpal-HIV-Gag(c) administered ex vivo to separated white blood cells on 4 occasions at 4 weekly intervals. |
| Diluent | Placebo comparator | Other: Dimethyl SulfoxideAdministered ex vivo to separated white blood cells on 4 occasions at 4 weekly intervals. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- Provision of written informed consent
- Documented laboratory diagnosis of HIV 1 infection
- Documented HIV clade of infection
- 18 - 60 years of age, inclusive
- Stable antiretroviral therapy (ART) regimen containing at least 3 active ART agents for at least 2 months prior to Baseline
Key exclusion criteria (24 listed)
- Any serious or active medical or psychiatric illness which, in the opinion of the Investigator, would interfere with treatment, assessment, compliance with the protocol, or subject safety. This would include any active clinically significant renal, cardiac, pulmonary, vascular, or metabolic (thyroid disorders, adrenal disease) illness, or malignancy
- Hepatitis B virus surface antigen, or Hepatitis C virus (HCV) antibody and HCV-RNA positive at Screening
- Female subjects who are lactating and those of reproductive potential with a positive urine pregnancy test at either Screening or Baseline
- A new AIDS-defining condition diagnosed within 42 days prior to Baseline visit
- Known or suspected allergy to Dimethyl Sulfoxide
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Opal-HIV-Gag(c) Low Dose | Biological | Opal-HIV-Gag(c) |
| Opal-HIV-Gag(c) Medium dose | Biological | Opal-HIV-Gag(c) |
| Opal-HIV-Gag(c) High dose | Biological | Opal-HIV-Gag(c) |
| Dimethyl Sulfoxide | Other | Diluent |
Primary outcome
Safety
Time frame: Several points throughout the 12 week active phase and 12 week and follow up period
Examined through treatment-emergent adverse events, vital signs and routine laboratory screening.
2 secondary outcomes
Immunogenicity
Time frame: Several points throughout the 12 week active phase and 12 week and follow up period
Impact on HIV infection
Time frame: Several points throughout the 12 week active phase and 12 week and follow up period
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Mar 2018.
- Derived from this study: PubMed 24124451Kloverpris HN, Jackson A, Handley A, Hayes P, Gilmour J, Riddell L, Chen F, Atkins M, Boffito M, Walker BD, Ackland J, Sullivan M, Goulder P. Non-immunogenicity of overlapping gag peptides pulsed on autologous cells after vaccination of HIV infected individuals. PLoS One. 2013 Oct 4;8(10):e74389. doi: 10.1371/journal.pone.0074389. eCollection 2013.
- Derived from this study: PubMed 24069230Jackson A, Kloverpris HN, Boffito M, Handley A, Atkins M, Hayes P, Gilmour J, Riddel L, Chen F, Bailey-Tippets M, Walker B, Ackland J, Sullivan M, Goulder P. A randomised, placebo-controlled, first-in-human study of a novel clade C therapeutic peptide vaccine administered ex vivo to autologous white blood cells in HIV infected individuals. PLoS One. 2013 Sep 17;8(9):e73765. doi: 10.1371/journal.pone.0073765. eCollection 2013.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marta Boffito, MD PhD principal investigator
St Stephen's AIDS Trust
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Opal-HIV-Gag(c) Low Dose, Opal-HIV-Gag(c) Medium dose and Opal-HIV-Gag(c) High dose in people with HIV Infections, run by Medicines Development for Global Health at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 22 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early. Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety (time frame: Several points throughout the 12 week active phase and 12 week and follow up period). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01123915, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Mar 2018.