HIV-1 InfectionPhase 2ERAMUNE-01NCT01019551
Therapeutic Intensification Plus Immunomodulation in HIV-infected Patients
A Phase 2 study testing ART Intensification and Immunomodulation in people with HIV-1 Infection, run by Objectif Recherche Vaccins SIDA at 5 sites in 4 countries.
Trial summary
Viral eradication in selected HIV-infected patients is possible with intensive antiretroviral therapy plus immunomodulation Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- HIV-1 Infection
- What is being tested?
- ART Intensification and Immunomodulation
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 5 sitesin 4 countries
- Study dates
- Sep 2010to Feb 2013
- Phase
- Phase 2
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- HIV-1 infection, documented by any licensed ELISA test kit and confirmed by Western Blot at any time prior to study entry. HIV-1 culture, HIV-1 antigen, plasma HIV-1 RNA, or a second antibody test by a method other than ELISA is acceptable as an alternative confirmatory test
- 18 ≤ Age ≤ 70 years
- At least 3 years of suppressive ART without any interruption (less than one month cumulative),
- ART treatment unchanged in the 3 months prior to screening
- One HIV plasma viral load (RNA) documented at least 3 years prior to entry, and at least 2 HIV plasma viral loads (RNA) documented per year thereafter
- HIV plasma viral load (RNA) ≤ 500 copies/ml at least 3 years prior to entry and HIV plasma viral load ≤ 500 copies/ml for ≥ 90% of the measures thereafter
Show all 12Show fewer
- HIV plasma viral load (RNA) below the limit of detection for all values within the past year. Note: the assay used must have a lower limit of detection of 75 copies/ml or less
- CD4+ count ≥ 350 cells/mm3 within 60 days of entry
- 10 ≤ Proviral DNA ≤ 1000 copies/106 PBMCs within 60 days of entry
- Documented laboratory values: Haemoglobin ≥ 10 g/dl, Platelets ≥ 100,000 per microliter, Hepatic transaminases ≤ 2.5 x ULN, Creatinine clearance ≥ 50 ml/min by the Cockcroft-Gault equation
- All subjects must agree not to participate in the conception process (e.g. active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization), and if participating in sexual activity that could lead to pregnancy, the subject/partner must use at least two reliable forms of contraceptives (condoms, with or without spermicidal agent, a diaphragm or cervical cap with spermicide, an IUD, or hormone-based contraception), while receiving study treatment and for 6 weeks after stopping study treatment
- Ability and willingness to provide informed consent.
Who cannot join
- Sexually active men and women who will not practice at least one form of barrier birth control (male partner using condoms, female partner using condoms, other barrier contraception, etc)
- Pregnancy as documented by a urine pregnancy test, or lactating women
- Hepatitis B antigen (HBsAg) positive
- Hepatitis C virus (HCV-Ab) positive or HCV RNA detectable
- Previous use of an integrase inhibitor (ie raltegravir) or a CCR5 inhibitor (ie maraviroc, vicriviroc). Use of raltegravir for non-treatment failure indications such as intensification and toxicity switches is allowed, provided that 1) virologic suppression was maintained before, during and after raltegravir treatment and 2) the patient has not received raltegravir treatment in the 6 months prior to study entry.
- Previous immunologic therapeutic intervention (e.g. IL-2, IL-7) within the past year
Show all 12Show fewer
- Participation in another clinical drug or device trial where the last dose of drug was within the past 30 days or an investigational medical device is currently implanted
- Diagnosis of cancer within the last 5 years (except basal cell cutaneous cancers and cutaneous KS not requiring systemic therapy)
- Co-morbid condition with an expected survival less than 12 months
- History of hypersensitivity to vaccination
- History of autoimmune disease, such as systemic lupus erythematosis (SLE) or Hashimoto's thyroiditis
- Active drug or alcohol use or dependence that, in the opinion of the center investigator, would interfere with adherence to study requirements.
Trial locations and contacts
5 sites in 4 countries.
5 sites in 4 countries
Spain2 sites
Fundacio Irsicaixa
Badalona, 08916
University Hospital Clinic of Barcelona
Barcelona, 08036
About this study
Official title: International, Multicenter, Randomized, Non-comparative Controlled Study of Therapeutic Intensification Plus Immunomodulation in HIV-infected Patients With Long-term Viral Suppression
Viral eradication in selected HIV-infected patients is possible with intensive antiretroviral therapy plus immunomodulation
Read the detailed description
The overall strategy of the ERAMUNE 01 Trial is to treat selected patients with an optimal synergistic antiretroviral regimen plus one or more immunomodulating agents. Among immunomodulating treatments the candidates include therapies from two functional classes: 1) agents that target actively replicating cells and 2) agents activating latently infected cells31.
The novelty of this approach is three-fold: first, the use of highly potent antiretroviral therapy combining drugs with different HIV enzymes targets or receptors and different penetrations in cells, with the aim to suppress virus to truly undetectable levels as measured by the most sophisticated viral quantification techniques; secondly, the addition of an immunomodulatory therapy that specifically targets viral reservoirs to this intensification strategy; and lastly, the rigorous selection of patients having already a low HIV reservoir as measured by peripheral blood HIV DNA content. To our knowledge, this type of strategy has not been implemented. We believe this strategy is feasible.
- Conditions
- HIV-1 Infection
- Being tested
- ART Intensification, Immunomodulation
- Keywords
- Controlled viremia, Viral reservoirs, Virus eradication, Therapeutic intensification, Immunointervention
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ART IntensificationDrug
Current ART regimen plus raltegravir and maraviroc Raltegravir : 400 mg PO BID for 56 weeks Maraviroc : 150, 300 or 600 mg PO BID depending on concomitant ART treatment, for 56 weeks
ImmunomodulationBiological
Starting at Week 8, 1 cycle of 3 injections (1 per week) of recombinant human Interleukin-7 (r-hIL-7 / CYT107) at a 20 µg/kg dose.
| Study group | Role | What they receive |
|---|---|---|
| ARM A : ART intensification alone | Experimental | Raltegravir PO 400 mg BID Maraviroc PO 150, 300 or 600 mg BID depending on the concomitant ART regimen Receives: Drug: ART Intensification |
| ARM B : ART intensification + Immunomodulation | Experimental | Raltegravir PO 400 mg BID during 56 weeks Maraviroc PO 150, 300 or 600 mg BID depending on the concomitant ART regimen during 56 weeks 3 weekly injections of r-hIL-7 (CYT107) at a 20 micrograms/kg dose starting at Week 8 Receives: Drug: ART Intensification; Biological: Immunomodulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Decrease from baseline in HIV proviral DNA in the PBMCs at week 56 of at least 0.5 log, as expressed as numbers of HIV DNA copies per million PBMCs
Measured: End of study
Secondary outcomes (12)
Percentage of patients with undetectable HIV DNA (< 1 copy/million PBMCs) after 56 weeks
Measured: End of study
Change from baseline in HIV proviral DNA in any of the sub-compartments explored (gut lymphoid tissue), as expressed as numbers of HIV DNA copies per million mononuclear cells
Measured: From Day 0 to Week 56
Change from baseline in HIV proviral DNA in the CD4 T cell subsets, as expressed as numbers of HIV DNA copies per million CD4 T cells
Measured: From Day 0 to Week 56
Changes from baseline in HIV plasma viral load (number of copies of HIV RNA per millilitre), measured by quantitative ultrasensitive PCR
Measured: From Day 0 to Week 56
Proportion of patients without inducible HIV RNA, DNA and/or p24
Measured: End of study
Changes from baseline in CD4 lymphocyte count
Measured: From Day 0 to Week 56
Changes in the activation and differentiation markers of the CD4 and CD8 peripheral blood T cells
Measured: End of study
Development of a mathematical model exploring the dynamics of the HIV-DNA decay
Measured: From Day 0 to Week 56
Development of a mathematical model exploring the dynamics of T cells activation (CD38)
Measured: From Day 0 to Week 56
Genetic determinants influencing HIV-1-specific immune response and HIV control
Measured: End of study
Antiretroviral drugs pharmacokinetics in the blood and rectal mucosa
Measured: From Day 0 to Week 56
Safety and tolerability of the intensified treatment regimen and immunomodulatory therapy
Measured: From Day 0 to Week 56
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Nov 2009 (estimated)
- Study startSep 2010
- Primary completionJul 2012
- Study completionFeb 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for HIV-1 InfectionStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- Objectif Recherche Vaccins SIDA
- Sponsor type
- University, hospital or other
- Collaborators
- Cytheris SA, Merck Sharp & Dohme LLC, Pfizer
- Responsible party
- Sponsor
- Investigators
- Christine KATLAMA, MD, Principal investigator, Groupe Hospitalier Pitie-SalpetriereSteven DEEKS, MD, Study chair, University of California, San FranciscoFrançois LECARDONNEL, MSc, Study director, ORVACS
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01019551
- Sponsor's protocol ID
- ORVACS 010
- Acronym
- ERAMUNE-01
- Status last verified
- Jun 2013
- First submitted
- 23 Nov 2009
- Last updated
- 13 Jun 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Murphy RL, Autran B, Katlama C, Brucker G, Debre P, Calvez V, Clotet B, Clumeck N, Costagliola D, Deeks SG, Dorrell L, Gatell J, Haase A, Klein M, Lazzarin A, McMichael AJ, Papagno L, Schacker TW, Wain-Hobson S, Walker BD, Youle M. A step ahead on the HIV collaboratory. Science. 2009 Jun 5;324(5932):1264-5. doi: 10.1126/science.324_1264b. No abstract available.
PubMed 19498149Lewin SR, Rouzioux C. HIV cure and eradication: how will we get from the laboratory to effective clinical trials? AIDS. 2011 Apr 24;25(7):885-97. doi: 10.1097/QAD.0b013e3283467041.
PubMed 21422987Lafeuillade A. Eliminating the HIV reservoir. Curr HIV/AIDS Rep. 2012 Jun;9(2):121-31. doi: 10.1007/s11904-012-0115-y.
PubMed 22415474Cohen J. The emerging race to cure HIV infections. Science. 2011 May 13;332(6031):784-5, 787-9. doi: 10.1126/science.332.6031.784. No abstract available.
PubMed 21566173Lewin SR, Evans VA, Elliott JH, Spire B, Chomont N. Finding a cure for HIV: will it ever be achievable? J Int AIDS Soc. 2011 Jan 24;14:4. doi: 10.1186/1758-2652-14-4.
PubMed 21255462Katlama C, Lambert-Niclot S, Assoumou L, Papagno L, Lecardonnel F, Zoorob R, Tambussi G, Clotet B, Youle M, Achenbach CJ, Murphy RL, Calvez V, Costagliola D, Autran B; EraMune-01 study team. Treatment intensification followed by interleukin-7 reactivates HIV without reducing total HIV DNA: a randomized trial. AIDS. 2016 Jan;30(2):221-30. doi: 10.1097/QAD.0000000000000894.
PubMed 26684819
Study at a glance
From the registry record, last updated by the sponsor on 13 Jun 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- International, Multicenter, Randomized, Non-comparative Controlled Study of Therapeutic Intensification Plus Immunomodulation in HIV-infected Patients With Long-term Viral Suppression
- ClinicalTrials.gov ID
- NCT01019551
- Acronym / sponsor ID
- ERAMUNE-01 / ORVACS 010
- Conditions
- HIV-1 Infection
- Keywords
- Controlled viremia, Viral reservoirs, Virus eradication, Therapeutic intensification, Immunointervention
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- Objectif Recherche Vaccins SIDAUniversity, hospital or other
- Collaborators
- Cytheris SA, Merck Sharp & Dohme LLC, Pfizer
- Study start
- Sep 2010
- Primary completion
- Jul 2012 (actual)
- Study completion
- Feb 2013 (actual)
- First posted
- 25 Nov 2009 (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.
Viral eradication in selected HIV-infected patients is possible with intensive antiretroviral therapy plus immunomodulation
Detailed description
The overall strategy of the ERAMUNE 01 Trial is to treat selected patients with an optimal synergistic antiretroviral regimen plus one or more immunomodulating agents. Among immunomodulating treatments the candidates include therapies from two functional classes: 1) agents that target actively replicating cells and 2) agents activating latently infected cells31.
The novelty of this approach is three-fold: first, the use of highly potent antiretroviral therapy combining drugs with different HIV enzymes targets or receptors and different penetrations in cells, with the aim to suppress virus to truly undetectable levels as measured by the most sophisticated viral quantification techniques; secondly, the addition of an immunomodulatory therapy that specifically targets viral reservoirs to this intensification strategy; and lastly, the rigorous selection of patients having already a low HIV reservoir as measured by peripheral blood HIV DNA content. To our knowledge, this type of strategy has not been implemented. We believe this strategy is feasible.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ARM A : ART intensification alone | Experimental | Drug: ART IntensificationRaltegravir PO 400 mg BID Maraviroc PO 150, 300 or 600 mg BID depending on the concomitant ART regimen |
| ARM B : ART intensification + Immunomodulation | Experimental | Drug: ART Intensification, Biological: ImmunomodulationRaltegravir PO 400 mg BID during 56 weeks Maraviroc PO 150, 300 or 600 mg BID depending on the concomitant ART regimen during 56 weeks 3 weekly injections of r-hIL-7 (CYT107) at a 20 micrograms/kg dose starting at Week 8 |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- HIV-1 infection, documented by any licensed ELISA test kit and confirmed by Western Blot at any time prior to study entry. HIV-1 culture, HIV-1 antigen, plasma HIV-1 RNA, or a second antibody test by a method other than ELISA is acceptable as an alternative confirmatory test
- 18 ≤ Age ≤ 70 years
- At least 3 years of suppressive ART without any interruption (less than one month cumulative),
- ART treatment unchanged in the 3 months prior to screening
- One HIV plasma viral load (RNA) documented at least 3 years prior to entry, and at least 2 HIV plasma viral loads (RNA) documented per year thereafter
Key exclusion criteria (12 listed)
- Sexually active men and women who will not practice at least one form of barrier birth control (male partner using condoms, female partner using condoms, other barrier contraception, etc)
- Pregnancy as documented by a urine pregnancy test, or lactating women
- Hepatitis B antigen (HBsAg) positive
- Hepatitis C virus (HCV-Ab) positive or HCV RNA detectable
- Previous use of an integrase inhibitor (ie raltegravir) or a CCR5 inhibitor (ie maraviroc, vicriviroc). Use of raltegravir for non-treatment failure indications such as intensification and toxicity switches is allowed, provided that 1) virologic suppression was maintained before, during and after raltegravir treatment and 2) the patient has not received raltegravir treatment in the 6 months prior to study entry.
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 |
|---|---|---|
| ART IntensificationCurrent ART regimen plus raltegravir and maraviroc Raltegravir : 400 mg PO BID for 56 weeks Maraviroc : 150, 300 or 600 mg PO BID depending on concomitant ART treatment, for 56 weeks | Drug | ARM A : ART intensification alone, ARM B : ART intensification + Immunomodulation |
| ImmunomodulationStarting at Week 8, 1 cycle of 3 injections (1 per week) of recombinant human Interleukin-7 (r-hIL-7 / CYT107) at a 20 µg/kg dose. | Biological | ARM B : ART intensification + Immunomodulation |
Primary outcome
Decrease from baseline in HIV proviral DNA in the PBMCs at week 56 of at least 0.5 log, as expressed as numbers of HIV DNA copies per million PBMCs
Time frame: End of study
12 secondary outcomes
Percentage of patients with undetectable HIV DNA (< 1 copy/million PBMCs) after 56 weeks
Time frame: End of study
Change from baseline in HIV proviral DNA in any of the sub-compartments explored (gut lymphoid tissue), as expressed as numbers of HIV DNA copies per million mononuclear cells
Time frame: From Day 0 to Week 56
Change from baseline in HIV proviral DNA in the CD4 T cell subsets, as expressed as numbers of HIV DNA copies per million CD4 T cells
Time frame: From Day 0 to Week 56
Changes from baseline in HIV plasma viral load (number of copies of HIV RNA per millilitre), measured by quantitative ultrasensitive PCR
Time frame: From Day 0 to Week 56
Proportion of patients without inducible HIV RNA, DNA and/or p24
Time frame: End of study
Changes from baseline in CD4 lymphocyte count
Time frame: From Day 0 to Week 56
Changes in the activation and differentiation markers of the CD4 and CD8 peripheral blood T cells
Time frame: End of study
Development of a mathematical model exploring the dynamics of the HIV-DNA decay
Time frame: From Day 0 to Week 56
Development of a mathematical model exploring the dynamics of T cells activation (CD38)
Time frame: From Day 0 to Week 56
Genetic determinants influencing HIV-1-specific immune response and HIV control
Time frame: End of study
Antiretroviral drugs pharmacokinetics in the blood and rectal mucosa
Time frame: From Day 0 to Week 56
Safety and tolerability of the intensified treatment regimen and immunomodulatory therapy
Time frame: From Day 0 to Week 56
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jun 2013.
- Background: PubMed 19498149Murphy RL, Autran B, Katlama C, Brucker G, Debre P, Calvez V, Clotet B, Clumeck N, Costagliola D, Deeks SG, Dorrell L, Gatell J, Haase A, Klein M, Lazzarin A, McMichael AJ, Papagno L, Schacker TW, Wain-Hobson S, Walker BD, Youle M. A step ahead on the HIV collaboratory. Science. 2009 Jun 5;324(5932):1264-5. doi: 10.1126/science.324_1264b. No abstract available.
- Background: PubMed 21422987Lewin SR, Rouzioux C. HIV cure and eradication: how will we get from the laboratory to effective clinical trials? AIDS. 2011 Apr 24;25(7):885-97. doi: 10.1097/QAD.0b013e3283467041.
- Background: PubMed 22415474Lafeuillade A. Eliminating the HIV reservoir. Curr HIV/AIDS Rep. 2012 Jun;9(2):121-31. doi: 10.1007/s11904-012-0115-y.
- Background: PubMed 21566173Cohen J. The emerging race to cure HIV infections. Science. 2011 May 13;332(6031):784-5, 787-9. doi: 10.1126/science.332.6031.784. No abstract available.
- Background: PubMed 21255462Lewin SR, Evans VA, Elliott JH, Spire B, Chomont N. Finding a cure for HIV: will it ever be achievable? J Int AIDS Soc. 2011 Jan 24;14:4. doi: 10.1186/1758-2652-14-4.
- Derived from this study: PubMed 26684819Katlama C, Lambert-Niclot S, Assoumou L, Papagno L, Lecardonnel F, Zoorob R, Tambussi G, Clotet B, Youle M, Achenbach CJ, Murphy RL, Calvez V, Costagliola D, Autran B; EraMune-01 study team. Treatment intensification followed by interleukin-7 reactivates HIV without reducing total HIV DNA: a randomized trial. AIDS. 2016 Jan;30(2):221-30. doi: 10.1097/QAD.0000000000000894.
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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.
Christine KATLAMA, MD principal investigator
Groupe Hospitalier Pitie-Salpetriere
Steven DEEKS, MD study chair
University of California, San Francisco
François LECARDONNEL, MSc study director
ORVACS
5 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ART Intensification and Immunomodulation in people with HIV-1 Infection, run by Objectif Recherche Vaccins SIDA at 5 sites in 4 countries.
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 12 inclusion and 12 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: finished, as of the sponsor's last update on 13 Jun 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Spain, France, Italy, 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. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Decrease from baseline in HIV proviral DNA in the PBMCs at week 56 of at least 0.5 log, as expressed as numbers of HIV DNA copies per million PBMCs (time frame: End of study). 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 NCT01019551, which also lists 6 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 13 Jun 2013.