HIV InfectionsPhase 1NCT02028403
Safety and Immune Response of BMS-936559 in HIV-Infected People Taking Combination Antiretroviral Therapy
A Phase 1 study testing BMS-936559 in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 5 sites in United States.
Trial summary
People infected with HIV may have low levels of the virus in their body, even if they are taking HIV medications. This study will evaluate the safety, pharmacokinetics (PK) (which is how the body interacts with drugs), and immune response to BMS-936559, a drug that will be administered by an intravenous (IV) infusion… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- HIV Infections
- What is being tested?
- BMS-936559
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 8 participants
- Where
- 5 sitesUnited States
- Study dates
- Jun 2014to Nov 2015
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 RNA assay. More information on this criterion is available in the protocol.
- Receiving a stable cART regimen containing at least three agents (not including ritonavir if less than a 200 mg total daily dose) with no changes in the components of their antiretroviral therapy for at least 90 days prior to study entry. NOTE: One of the agents must include an integrase inhibitor, a non-nucleoside reverse transcriptase inhibitor (NNRTI), or a boosted protease inhibitor (PI).
- CD4 cell count greater than or equal to 350 cells/mm^3 obtained within 90 days prior to study entry at any U.S. laboratory that has a clinical laboratory improvement amendments (CLIA) certification or its equivalent
- Plasma HIV-1 RNA below detected limit obtained by Food and Drug Administration (FDA)-approved assays (limit of detection: 75, 50, 40, or 20) for greater than or equal to 2 years on cART. Participants must have at least one documented HIV-1 RNA less than the limit of detection 12-24 months prior to screening and one HIV-1 RNA less than the limit of detection within 12 months prior to screening. NOTE: A single unconfirmed plasma HIV-1 RNA greater than the limit of detection but less than 1,000 copies/mL is allowed if followed by HIV-1 RNA below detectable limits, but none in the 6 months prior to screening.
- Plasma HIV-1 RNA level of less than 40 copies/mL obtained by the Abbott m2000 assay or less than 20 copies/mL by the Roche Taqman v2.0 assay within 90 days prior to entry. The protocol team should be notified as soon as possible if the HIV-1 RNA level is above the limit of detection for either assay.
- Plasma HIV-1 RNA greater than or equal to 0.4 copies/mL by single copy assay (SCA) within 120 days prior to entry
Show all 26Show fewer
- The following laboratory values obtained within 60 days prior to entry by any U.S. laboratory that has a CLIA certification or its equivalent:
- Absolute neutrophil count (ANC) greater than or equal to 1,000 cells/mm^3
- Hemoglobin greater than or equal to 14.0 g/dL for men and greater than or equal to 12.0 g/dL for women
- Platelet count greater than or equal to 75,000/mm^3
- Creatinine clearance greater than or equal to 50 mL/min estimated by the Cockcroft-Gault equation. NOTE: A program for calculating creatinine clearance by the Cockcroft-Gault method is available on www.fstrf.org.
- Alanine aminotransferase (ALT) (SGPT) less than or equal to 2.5 times upper limit of normal (ULN)
- A.M. cortisol within normal limits
- Fasting blood sugar within normal limits
- Total bilirubin less than or equal to 1.6 x ULN. NOTE: If the participant is on an atazanavir-containing therapy then a direct bilirubin should be measured instead of the total bilirubin and must be less than or equal to 1.0 mg/dL.
- The following laboratory values obtained within 90 days prior to entry by any U.S. laboratory that has a CLIA certification or its equivalent:
- Thyroid stimulating hormone (TSH) and free T4 level within normal limits
- Hemoglobin A1c (HgbA1c) within normal limits
- Hepatitis C virus (HCV) antibody negative result within 90 days prior to study entry or, if the HCV antibody result is positive, a negative HCV RNA result prior to study entry. Participants who have received HCV treatment in the last 5 years will be excluded.
- Negative hepatitis B surface antigen (HBsAg) result obtained within 90 days prior to study entry
- Karnofsky performance score greater than or equal to 90 within 60 days prior to entry
- Documentation of the availability of the stored pre-entry plasma specimens for HIV-1 RNA SCA determination and stored pre-entry peripheral blood mononuclear cell (PBMC) specimens for CD8 T-cell assays. Sites must receive confirmation from the processing lab via phone, e-mail, or fax, that specimens have been entered into the AIDS Clinical Trials Group's (ACTG's) Laboratory Data Management System (LDMS).
- Ability and willingness of participant or legal guardian/representative to provide informed consent
- Ability and willingness of participant to continue cART throughout the study
- Ability to construct a fully active alternative cART regimen in the event of virologic failure on the current ART regimen
- An ophthalmology exam within 180 days prior to entry and a copy of the results of the exam. NOTE: Ophthalmologic exams done to meet enrollment criteria must be performed by a licensed ophthalmologist within 180 days of the study entry visit. Results of the exam must be available for review and made part of the clinical record.
Who cannot join
- History of malignancy within the last 5 years or current malignancy requiring cytotoxic therapy. NOTE: A history of non-melanoma skin cancer (e.g., basal cell carcinoma or squamous cell skin cancer) is not exclusionary.
- History of HIV-related opportunistic infections within the last 5 years. More information on this criterion is available in the protocol.
- Current chronic, acute, or recurrent bacterial, fungal, or viral (other than HIV) infections that are serious, in the opinion of the site investigator, and required systemic therapy within 30 days prior to entry
- History of or active autoimmune disorders including but not limited to inflammatory bowel diseases, scleroderma, severe psoriasis, myocarditis, uveitis, pneumonitis, systemic lupus erythematosus, rheumatoid arthritis, optic neuritis, myasthenia gravis, adrenal insufficiency, hypothyroidism and/or hyperthyroidism, autoimmune thyroiditis, or sarcoidosis. More information on this criterion is available in the protocol.
- History of inflammatory disorders of the eye including uveitis (iritis, endophthalmitis, scleritis, retinitis - including viral or other infectious retinitis) and chronic or recurrent post-operative inflammation. NOTE: A history of self-limited conjunctivitis, blepharitis, or hordeolum (stye) are NOT exclusions.
- Previous ocular treatment with silicone oil tamponade (for complex retinal detachment)
Show all 26Show fewer
- Intraocular surgery within 90 days prior to entry or the anticipated need for intraocular surgery during the course of the study
- Intraocular laser or cryotherapy within 90 days prior to entry or the anticipated need for intraocular laser or cryotherapy during the course of the study
- Evidence on eye exam of active or previous ocular inflammation or uveitis
- Previous history of serious ocular trauma (e.g., penetrating trauma of the eye)
- Severe cataract or other ocular abnormality that precludes adequate examination of the posterior chamber and fundus
- Active infection or inflammation of the eye within 30 days prior to entry that requires systemic or topical therapy or, in the opinion of the site investigator, would complicate on-study evaluation and patient safety. NOTE: A history of self-limited allergic conjunctivitis is NOT an exclusion. More information on this criterion is available in the protocol.
- Immune deficiency other than HIV
- Breastfeeding
- Known allergy/sensitivity or any hypersensitivity to components of BMS-936559 (anti-PD-L1) or its formulation
- Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements
- Acute or serious illness, in the opinion of the site investigator, requiring systemic treatment and/or hospitalization within 30 days prior to entry
- Use of immunomodulators (e.g., interleukins, interferons, cyclosporine), HIV vaccine, systemic cytotoxic chemotherapy, or investigational therapy within 60 days prior to study entry. NOTE: Participants receiving stable physiologic glucocorticoid doses, defined as prednisone less than or equal to 10 mg/day or the equivalent, will not be excluded. Stable physiologic glucocorticoid doses should not be discontinued for the duration of the study. In addition, participants receiving inhaled or topical corticosteroids will not be excluded.
- Intent to use immunomodulators (e.g., IL-2, IL-12, interferons, or tumor necrosis factor [TNF] modifiers) during the course of the study
- Any vaccination within 30 days prior to screening SCA, pre-entry, or entry. Individuals who require vaccination will delay screening SCA until 30 days post-vaccination. Alternatively, vaccinations can occur following the screening SCA, provided they occur greater than or equal to 30 days prior to pre-entry or entry.
- Current HCV antiviral therapy or participants who have received HCV treatment in the last 5 years
- Positive tuberculosis (TB) purified protein derivative (PPD) skin test or interferon-gamma release assay (IGRA) at screening. NOTE: Participants with a prior positive PPD or IGRA who have not completed prophylaxis treatment will be excluded.
- Women of reproductive potential. More information on this criterion is available in the protocol.
- History of chronic obstructive pulmonary disease (COPD)
- Type I and type II diabetes mellitus
- Participants weighing less than 50 kg or greater than 200 kg. NOTE: For participants weighing between 50 kg to 52.9 kg, sites must consult with the A5326 protocol team prior to enrollment. The allowable blood volume to be drawn in an 8-week period for these participants may be less than participants weighing greater than or equal to 53 kg.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
University of Colorado Hospital CRS
Aurora, Colorado, 80045
Chapel Hill CRS
Chapel Hill, North Carolina, 27599
Cincinnati Clinical Research Site
Cincinnati, Ohio, 45219
Vanderbilt Therapeutics (VT) CRS
Nashville, Tennessee, 37204
Washington University Therapeutics (WT) CRS
St Louis, Missouri, 63110-1010
About this study
Official title: Safety, Pharmacokinetics and Immunotherapeutic Activity of an Anti-PD-L1 Antibody (BMS-936559) in HIV-1 Infected Participants on Suppressive cART: A Phase I, Double-Blind, Placebo-Controlled, Ascending Single Dose Study
People infected with HIV may have low levels of the virus in their body, even if they are taking HIV medications. This study will evaluate the safety, pharmacokinetics (PK) (which is how the body interacts with drugs), and immune response to BMS-936559, a drug that will be administered by an intravenous (IV) infusion, in HIV-infected people receiving combination antiretroviral therapy (cART) who have viral load levels below the limit of detection.
Read the detailed description
People infected with HIV who are taking cART and have low viral load levels may still have reservoirs of HIV remaining in their body. BMS-936559 is a drug that has been studied in previous clinical trials to treat various types of cancer. The purpose of this study is to evaluate the safety, PK, and immunotherapeutic activity of a single dose of BMS-936559 (administered by an IV infusion) in HIV-infected people who are receiving cART and who have viral loads below the limit of detection. Researchers will also evaluate whether BMS-936559 can reduce hidden reservoirs of HIV.
Participants will be enrolled in four cohorts. Within each cohort, participants will be randomly assigned to receive BMS-936559 (Cohort 1: 0.3 mg/kg; Cohort 2: 1 mg/kg; Cohort 3: 3 mg/kg; or Cohort 4: 10 mg/kg) or placebo. The four cohorts will be enrolled sequentially, with researchers reviewing safety data of the cohort before enrolling participants in the next cohort.
Prior to study entry, all participants must have an eye exam and an electrocardiogram (ECG). At study entry, participants will undergo a medical and medication history review, physical examination, an eye exam, and a blood collection. Some female participants will have a pregnancy test. All participants will then receive a single IV infusion of their assigned dose of BMS-936559 or placebo. The infusion will occur over a period of 60 minutes, and participants will remain in the clinic for observation for an additional 12 hours. Additional study visits will occur at Days 3, 7, 14, 28, and Weeks 10, 16, 24, 36, and 48. These study visits may include a physical examination, blood collection, adherence assessments, and PK evaluations. Some participants may have additional eye exams during the study, on an as-needed basis.
- Conditions
- HIV Infections
- Being tested
- BMS-936559, Placebo for BMS-936559
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BMS-936559Drug
0.3 mg/kg, 1 mg/kg, 3 mg/kg, or 10 mg/kg of BMS-936559, depending on which cohort participants are enrolled in, administered as an intravenous (IV) infusion
Placebo for BMS-936559Drug
Sodium chloride for injection 0.9%, USP, administered as an IV infusion
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1A: single dose 0.3 mg/kg BMS-936559 | Experimental | Participants will receive 0.3 mg/kg of BMS-936559, administered as a single infusion once at study entry. Receives: Drug: BMS-936559 |
| Cohort 1B: single dose placebo for BMS-936559 | Placebo comparator | Participants will receive placebo for BMS-936559, administered as a single infusion once at study entry. Receives: Drug: Placebo for BMS-936559 |
| Cohort 2A: single dose 1 mg/kg BMS-936559 | Experimental | Participants will receive 1 mg/kg of BMS-936559, administered as a single infusion once at study entry. Receives: Drug: BMS-936559 |
| Cohort 2B: single dose placebo for BMS-936559 | Placebo comparator | Participants will receive placebo for BMS-936559, administered as a single infusion once at study entry. Receives: Drug: Placebo for BMS-936559 |
| Cohort 3A: single dose 3 mg/kg BMS-936559 | Experimental | Participants will receive 3 mg/kg of BMS-936559, administered as a single infusion once at study entry. Receives: Drug: BMS-936559 |
| Cohort 3B: single dose placebo for BMS-936559 | Placebo comparator | Participants will receive placebo for BMS-936559, administered as a single infusion once at study entry. Receives: Drug: Placebo for BMS-936559 |
| Cohort 4A: single dose 10 mg/kg BMS-936559 | Experimental | Participants will receive 10 mg/kg of BMS-936559, administered as a single infusion once at study entry. Receives: Drug: BMS-936559 |
| Cohort 4B: single dose placebo for BMS-936559 | Placebo comparator | Participants will receive placebo for BMS-936559, administered as a single infusion once at study entry. Receives: Drug: Placebo for BMS-936559 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Occurrence of a Grade 3 or greater adverse event (AE), including sign/symptom, lab toxicity, or clinical event that is definitely, probably, or possibly related to study treatment
As judged by the core team, blinded to treatment arm; any time from study treatment administration until 28 days after the administration.
Measured: Measured through Day 28
Occurrence of a Grade 1 or > AE of all incident adrenal insufficiency or adrenal crisis (confirmed), myocarditis, pneumonitis, uveitis, immune-mediated hyperthyroidism or hypothyroidism, that is definitely, probably, or possibly related to study
As judged by the core team, blinded to treatment arm; any time from study treatment administration until 28 days after the administration.
(Pneumonitis is Category A, B, or C)
Measured: Measured through Day 28
Frequency of HIV-1 Gag-specific CD8 T-cells by intracellular staining for interferon (IFN)-gamma at baseline and after treatment (through Day 28)
Measured: Measured through Day 28
HIV-1 RNA by single copy assay (SCA) at baseline and after treatment (through Day 28)
Measured: Measured through Day 28
Secondary outcomes (16)
PK parameters from non-compartmental analysis (area under curve [AUC], Cmax, V, Tmax, CL/F, t1/2)
Measured: Measured through Week 48
Exploratory pharmacodynamic parameters (Emax, EC50)
Measured: Measured through Week 48
HIV-1 DNA at baseline and after treatment
Measured: Measured through Week 48
Programmed cell death 1 ligand 1 (PD-L1) receptor occupancy
Measured: Measured through Week 48
Proportion of total and HIV-1 gag-specific CD8 T-cells expressing programmed cell death 1 (PD-1), PD-L1, and other exhaustion markers
Measured: Measured through Week 48
CD107a mobilization and carboxyfluorescein diacetate succinimidyl ester (CFSE) dilution of HIV-1 gag-specific CD8 T-cells
Measured: Measured through Week 48
Polyfunctionality of HIV-1 specific CD8 and CD4 T-cells
Measured: Measured through Week 48
CD38 and human leukocyte antigen-DR (HLA-DR) expression on CD8 T-cells
Measured: Measured through Week 48
Gene expression profiles in whole blood
Measured: Measured through Week 48
Detection of antibody to study treatment in plasma
Measured: Measured through Week 48
Occurrence of a Grade 3 or greater AE, including sign/symptom, lab toxicity, or clinical event that is definitely, probably, or possibly related to study treatment
As judged by the core team, blinded to treatment arm; any time greater than or equal to 29 days after the study treatment administration
Measured: Measured through Week 48
Occurrence of a Grade 1 or > AE of all incident adrenal insufficiency or adrenal crisis (confirmed), myocarditis, pneumonitis, uveitis, immune mediated hyperthyroidism or hypothyroidism, that is definitely, probably, or possibly related to study
As judged by the core team, blinded to treatment arm; any time greater than or equal to 29 days after the study treatment administration
Measured: Measured through Week 48
2-long terminal repeat (2LTR) circle DNA at baseline and after treatment
Measured: Measured through Week 48
Cell-associated HIV-1 RNA at baseline and after treatment
Measured: Measured through Week 48
RNA/DNA ratios in total CD4 cells at baseline and after treatment
Measured: Measured through Week 48
Expression of programmed cell death 1 ligand 2 (PD-L2) on dendritic cells and monocyte-derived macrophages
Measured: Measured through Week 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jan 2014 (estimated)
- Study startJun 2014
- Primary completionNov 2015
- Study completionNov 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- 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
- 8 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Joseph Eron Jr., MD, Study chair, University of North Carolina, Chapel Hill
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02028403
- Sponsor's protocol ID
- A5326
- Other IDs
- 11921
- Status last verified
- Oct 2016
- First submitted
- 3 Jan 2014
- Last updated
- 5 Nov 2021
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Gay CL, Bosch RJ, Ritz J, Hataye JM, Aga E, Tressler RL, Mason SW, Hwang CK, Grasela DM, Ray N, Cyktor JC, Coffin JM, Acosta EP, Koup RA, Mellors JW, Eron JJ; AIDS Clinical Trials 5326 Study Team. Clinical Trial of the Anti-PD-L1 Antibody BMS-936559 in HIV-1 Infected Participants on Suppressive Antiretroviral Therapy. J Infect Dis. 2017 Jun 1;215(11):1725-1733. doi: 10.1093/infdis/jix191.
PubMed 28431010
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety, Pharmacokinetics and Immunotherapeutic Activity of an Anti-PD-L1 Antibody (BMS-936559) in HIV-1 Infected Participants on Suppressive cART: A Phase I, Double-Blind, Placebo-Controlled, Ascending Single Dose Study
- ClinicalTrials.gov ID
- NCT02028403
- Acronym / sponsor ID
- A5326
- Conditions
- HIV Infections
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- Jun 2014
- Primary completion
- Nov 2015 (actual)
- Study completion
- Nov 2015 (actual)
- First posted
- 7 Jan 2014 (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.
People infected with HIV may have low levels of the virus in their body, even if they are taking HIV medications. This study will evaluate the safety, pharmacokinetics (PK) (which is how the body interacts with drugs), and immune response to BMS-936559, a drug that will be administered by an intravenous (IV) infusion, in HIV-infected people receiving combination antiretroviral therapy (cART) who have viral load levels below the limit of detection.
Detailed description
People infected with HIV who are taking cART and have low viral load levels may still have reservoirs of HIV remaining in their body. BMS-936559 is a drug that has been studied in previous clinical trials to treat various types of cancer. The purpose of this study is to evaluate the safety, PK, and immunotherapeutic activity of a single dose of BMS-936559 (administered by an IV infusion) in HIV-infected people who are receiving cART and who have viral loads below the limit of detection. Researchers will also evaluate whether BMS-936559 can reduce hidden reservoirs of HIV.
Participants will be enrolled in four cohorts. Within each cohort, participants will be randomly assigned to receive BMS-936559 (Cohort 1: 0.3 mg/kg; Cohort 2: 1 mg/kg; Cohort 3: 3 mg/kg; or Cohort 4: 10 mg/kg) or placebo. The four cohorts will be enrolled sequentially, with researchers reviewing safety data of the cohort before enrolling participants in the next cohort.
Prior to study entry, all participants must have an eye exam and an electrocardiogram (ECG). At study entry, participants will undergo a medical and medication history review, physical examination, an eye exam, and a blood collection. Some female participants will have a pregnancy test. All participants will then receive a single IV infusion of their assigned dose of BMS-936559 or placebo. The infusion will occur over a period of 60 minutes, and participants will remain in the clinic for observation for an additional 12 hours. Additional study visits will occur at Days 3, 7, 14, 28, and Weeks 10, 16, 24, 36, and 48. These study visits may include a physical examination, blood collection, adherence assessments, and PK evaluations. Some participants may have additional eye exams during the study, on an as-needed basis.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| Cohort 1A: single dose 0.3 mg/kg BMS-936559 | Experimental | Drug: BMS-936559Participants will receive 0.3 mg/kg of BMS-936559, administered as a single infusion once at study entry. |
| Cohort 1B: single dose placebo for BMS-936559 | Placebo comparator | Drug: Placebo for BMS-936559Participants will receive placebo for BMS-936559, administered as a single infusion once at study entry. |
| Cohort 2A: single dose 1 mg/kg BMS-936559 | Experimental | Drug: BMS-936559Participants will receive 1 mg/kg of BMS-936559, administered as a single infusion once at study entry. |
| Cohort 2B: single dose placebo for BMS-936559 | Placebo comparator | Drug: Placebo for BMS-936559Participants will receive placebo for BMS-936559, administered as a single infusion once at study entry. |
| Cohort 3A: single dose 3 mg/kg BMS-936559 | Experimental | Drug: BMS-936559Participants will receive 3 mg/kg of BMS-936559, administered as a single infusion once at study entry. |
| Cohort 3B: single dose placebo for BMS-936559 | Placebo comparator | Drug: Placebo for BMS-936559Participants will receive placebo for BMS-936559, administered as a single infusion once at study entry. |
| Cohort 4A: single dose 10 mg/kg BMS-936559 | Experimental | Drug: BMS-936559Participants will receive 10 mg/kg of BMS-936559, administered as a single infusion once at study entry. |
| Cohort 4B: single dose placebo for BMS-936559 | Placebo comparator | Drug: Placebo for BMS-936559Participants will receive placebo for BMS-936559, administered as a single infusion once at study entry. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (26 listed)
- HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 RNA assay. More information on this criterion is available in the protocol.
- Receiving a stable cART regimen containing at least three agents (not including ritonavir if less than a 200 mg total daily dose) with no changes in the components of their antiretroviral therapy for at least 90 days prior to study entry. NOTE: One of the agents must include an integrase inhibitor, a non-nucleoside reverse transcriptase inhibitor (NNRTI), or a boosted protease inhibitor (PI).
- CD4 cell count greater than or equal to 350 cells/mm^3 obtained within 90 days prior to study entry at any U.S. laboratory that has a clinical laboratory improvement amendments (CLIA) certification or its equivalent
- Plasma HIV-1 RNA below detected limit obtained by Food and Drug Administration (FDA)-approved assays (limit of detection: 75, 50, 40, or 20) for greater than or equal to 2 years on cART. Participants must have at least one documented HIV-1 RNA less than the limit of detection 12-24 months prior to screening and one HIV-1 RNA less than the limit of detection within 12 months prior to screening. NOTE: A single unconfirmed plasma HIV-1 RNA greater than the limit of detection but less than 1,000 copies/mL is allowed if followed by HIV-1 RNA below detectable limits, but none in the 6 months prior to screening.
- Plasma HIV-1 RNA level of less than 40 copies/mL obtained by the Abbott m2000 assay or less than 20 copies/mL by the Roche Taqman v2.0 assay within 90 days prior to entry. The protocol team should be notified as soon as possible if the HIV-1 RNA level is above the limit of detection for either assay.
Key exclusion criteria (26 listed)
- History of malignancy within the last 5 years or current malignancy requiring cytotoxic therapy. NOTE: A history of non-melanoma skin cancer (e.g., basal cell carcinoma or squamous cell skin cancer) is not exclusionary.
- History of HIV-related opportunistic infections within the last 5 years. More information on this criterion is available in the protocol.
- Current chronic, acute, or recurrent bacterial, fungal, or viral (other than HIV) infections that are serious, in the opinion of the site investigator, and required systemic therapy within 30 days prior to entry
- History of or active autoimmune disorders including but not limited to inflammatory bowel diseases, scleroderma, severe psoriasis, myocarditis, uveitis, pneumonitis, systemic lupus erythematosus, rheumatoid arthritis, optic neuritis, myasthenia gravis, adrenal insufficiency, hypothyroidism and/or hyperthyroidism, autoimmune thyroiditis, or sarcoidosis. More information on this criterion is available in the protocol.
- History of inflammatory disorders of the eye including uveitis (iritis, endophthalmitis, scleritis, retinitis - including viral or other infectious retinitis) and chronic or recurrent post-operative inflammation. NOTE: A history of self-limited conjunctivitis, blepharitis, or hordeolum (stye) are NOT exclusions.
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 |
|---|---|---|
| BMS-9365590.3 mg/kg, 1 mg/kg, 3 mg/kg, or 10 mg/kg of BMS-936559, depending on which cohort participants are enrolled in, administered as an intravenous (IV) infusion | Drug | Cohort 1A: single dose 0.3 mg/kg BMS-936559, Cohort 2A: single dose 1 mg/kg BMS-936559, Cohort 3A: single dose 3 mg/kg BMS-936559, Cohort 4A: single dose 10 mg/kg BMS-936559 |
| Placebo for BMS-936559Sodium chloride for injection 0.9%, USP, administered as an IV infusion | Drug | Cohort 1B: single dose placebo for BMS-936559, Cohort 2B: single dose placebo for BMS-936559, Cohort 3B: single dose placebo for BMS-936559, Cohort 4B: single dose placebo for BMS-936559 |
Primary outcome
Occurrence of a Grade 3 or greater adverse event (AE), including sign/symptom, lab toxicity, or clinical event that is definitely, probably, or possibly related to study treatment
Time frame: Measured through Day 28
As judged by the core team, blinded to treatment arm; any time from study treatment administration until 28 days after the administration.
Occurrence of a Grade 1 or > AE of all incident adrenal insufficiency or adrenal crisis (confirmed), myocarditis, pneumonitis, uveitis, immune-mediated hyperthyroidism or hypothyroidism, that is definitely, probably, or possibly related to study
Time frame: Measured through Day 28
As judged by the core team, blinded to treatment arm; any time from study treatment administration until 28 days after the administration. (Pneumonitis is Category A, B, or C)
Frequency of HIV-1 Gag-specific CD8 T-cells by intracellular staining for interferon (IFN)-gamma at baseline and after treatment (through Day 28)
Time frame: Measured through Day 28
HIV-1 RNA by single copy assay (SCA) at baseline and after treatment (through Day 28)
Time frame: Measured through Day 28
16 secondary outcomes
PK parameters from non-compartmental analysis (area under curve [AUC], Cmax, V, Tmax, CL/F, t1/2)
Time frame: Measured through Week 48
Exploratory pharmacodynamic parameters (Emax, EC50)
Time frame: Measured through Week 48
HIV-1 DNA at baseline and after treatment
Time frame: Measured through Week 48
Programmed cell death 1 ligand 1 (PD-L1) receptor occupancy
Time frame: Measured through Week 48
Proportion of total and HIV-1 gag-specific CD8 T-cells expressing programmed cell death 1 (PD-1), PD-L1, and other exhaustion markers
Time frame: Measured through Week 48
CD107a mobilization and carboxyfluorescein diacetate succinimidyl ester (CFSE) dilution of HIV-1 gag-specific CD8 T-cells
Time frame: Measured through Week 48
Polyfunctionality of HIV-1 specific CD8 and CD4 T-cells
Time frame: Measured through Week 48
CD38 and human leukocyte antigen-DR (HLA-DR) expression on CD8 T-cells
Time frame: Measured through Week 48
Gene expression profiles in whole blood
Time frame: Measured through Week 48
Detection of antibody to study treatment in plasma
Time frame: Measured through Week 48
Occurrence of a Grade 3 or greater AE, including sign/symptom, lab toxicity, or clinical event that is definitely, probably, or possibly related to study treatment
Time frame: Measured through Week 48
Occurrence of a Grade 1 or > AE of all incident adrenal insufficiency or adrenal crisis (confirmed), myocarditis, pneumonitis, uveitis, immune mediated hyperthyroidism or hypothyroidism, that is definitely, probably, or possibly related to study
Time frame: Measured through Week 48
2-long terminal repeat (2LTR) circle DNA at baseline and after treatment
Time frame: Measured through Week 48
Cell-associated HIV-1 RNA at baseline and after treatment
Time frame: Measured through Week 48
RNA/DNA ratios in total CD4 cells at baseline and after treatment
Time frame: Measured through Week 48
Expression of programmed cell death 1 ligand 2 (PD-L2) on dendritic cells and monocyte-derived macrophages
Time frame: Measured through Week 48
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 5 Nov 2021.
- Derived from this study: PubMed 28431010Gay CL, Bosch RJ, Ritz J, Hataye JM, Aga E, Tressler RL, Mason SW, Hwang CK, Grasela DM, Ray N, Cyktor JC, Coffin JM, Acosta EP, Koup RA, Mellors JW, Eron JJ; AIDS Clinical Trials 5326 Study Team. Clinical Trial of the Anti-PD-L1 Antibody BMS-936559 in HIV-1 Infected Participants on Suppressive Antiretroviral Therapy. J Infect Dis. 2017 Jun 1;215(11):1725-1733. doi: 10.1093/infdis/jix191.
Related trials for HIV Infections
Not yet recruiting
HealthMpowerment Korea: Pilot Testing the Cultural Adaptation of a Digital HIV Intervention for Men Who Have Sex With Men in South Korea
HIV Infections, HIV Prevention and Care
Not yet recruiting
Prescribe to Prevent HIV: A Hybrid Trial Helping Addiction Clinics Prevent HIV & Infections Through Safer Drug Use Support
People Who Use Opioids/People With Opioid Use Disorder (OUD)
Recruiting
Evaluating the Impact of Using the B-OK Bottles for HIV and ART Literacy in South Africa
HIV, HIV Treatment
Recruiting
Trial Phase: Syndemic Adapted Medly Uganda
Mental Health
RecruitingObservational study
Olfactory Function and Model-Based Behavior in People Living With HIV and SUD
HIV, Substance Use Disorder
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.
Joseph Eron Jr., MD study chair
University of North Carolina, Chapel Hill
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing BMS-936559 in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 5 sites in United States.
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 26 inclusion and 26 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 5 Nov 2021. 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 United States. 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 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?
Occurrence of a Grade 3 or greater adverse event (AE), including sign/symptom, lab toxicity, or clinical event that is definitely, probably, or possibly related to study treatment (time frame: Measured through Day 28). The study lists 4 primary outcomes in all. 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 NCT02028403, which also lists 1 linked publication.
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 5 Nov 2021.