HIV (Human Immunodeficiency Virus)Phase 2NCT07881809
A Clinical Study of Ixazomib to Reactivate HIV and Reduce HIV Reservoir Size
A Phase 2 study testing Ixazomib 4 mg in people with HIV (Human Immunodeficiency Virus), run by National Institute of Allergy and Infectious Diseases (NIAID) at 20 sites in United States.
Trial summary
This study tests whether a medicine called ixazomib is safe for people living with HIV, and whether it can wake up HIV that is hiding in the body so the immune system and treatment can reach it. HIV can stay hidden inside cells even when antiretroviral therapy (ART) keeps the virus under control. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- HIV (Human Immunodeficiency Virus)
- What is being tested?
- Ixazomib 4 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 45 participants
- Where
- 20 sitesUnited States
- Study dates
- 23 Nov 2026to 5 Nov 2027
- Phase
- Phase 2
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
- Documented HIV-1 infection.
- Plasma HIV-1 RNA of 50 copies/mL or lower, for at least 48 weeks prior to study entry while on antiretroviral therapy. One blip above 50 but below 200 copies/mL in the preceding 48 weeks is permitted provided at least two other measurements in that period were 50 copies/mL or lower.
- Plasma HIV-1 RNA below the lower limit of quantification within 30 days prior to study entry.
- Receiving antiretroviral therapy for less than 10 years.
- On antiretroviral therapy for at least 48 weeks prior to study entry, with no interruption of more than 7 consecutive days in the 90 days prior to entry, and no change in regimen within 90 days prior to entry.
- CD4+ T cell count of at least 500 cells/mm^3 within 30 days prior to study entry.
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- Laboratory values within 30 days prior to study entry: absolute neutrophil count at least 1,000/mm^3; hemoglobin at least 10 g/dL (female participants) or at least 11 g/dL (male participants); platelet count at least 75,000/mm^3; estimated glomerular filtration rate at least 30 mL/min/1.73m^2; bilirubin no more than 1.5 times the upper limit of normal, or no more than 3 times the upper limit of normal if the isolated elevation is attributable to a participant medication or Gilbert syndrome, or direct bilirubin within the normal range.
- For participants who can become pregnant, a negative serum or urine pregnancy test within 24 hours prior to study entry.
- For participants who can become pregnant, agreement to use two methods of contraception from 10 days prior to study entry through 90 days after the last dose of study treatment. Egg donation is prohibited over the same period.
- For participants whose sexual activity could result in a partner becoming pregnant, agreement to use condoms from 10 days prior to study entry through 90 days after the last dose of study treatment. Sperm donation is prohibited over the same period.
- Negative hepatitis B surface antigen within 30 days prior to study entry.
- Negative hepatitis C antibody, or if positive, a negative HCV RNA PCR, within 30 days prior to study entry.
Who cannot join
- Untreated, active AIDS-defining illness.
- Receiving an HIV protease inhibitor or efavirenz as part of the antiretroviral regimen.
- Current pregnancy or breastfeeding.
- Receipt of an investigational HIV vaccine or HIV-specific monoclonal antibody, or participation in a trial of any investigational product, within 180 days prior to study entry, or expected participation in such a study during this study.
- Any current clinically significant acute or chronic medical condition other than HIV infection that in the investigator's opinion would preclude participation.
- Any history of peripheral neuropathy, or peripheral neuropathy detected during screening.
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- History of an HIV-associated malignancy, including Kaposi sarcoma or lymphoma of any type, treated with systemic chemotherapy or immunotherapy.
- Active or recent non-HIV-associated malignancy requiring systemic chemotherapy or surgery within 36 months prior to study entry, or for whom such therapy is expected within the following 12 months. Surgical removal of minor localized skin cancers is not exclusionary.
- Use of prohibited medications within 30 days prior to study entry or planned use during study participation.
- Known allergy, sensitivity, or hypersensitivity to ixazomib or its formulation.
- Active drug or alcohol use or dependence that, in the investigator's opinion, would interfere with adherence to study requirements.
- Acute or serious illness requiring systemic treatment or hospitalization within 30 days prior to study entry.
- Anticipated change in antiretroviral regimen during the 24 weeks following study entry.
- Current uncontrolled cardiovascular symptoms, including uncontrolled hypertension (systolic blood pressure above 140 mmHg or diastolic blood pressure above 90 mmHg), uncontrolled cardiac arrhythmia, symptomatic congestive heart failure, unstable angina, or myocardial infarction within 24 weeks prior to study entry.
- Any serious medical or psychiatric illness that in the investigator's opinion could interfere with completion of protocol treatment.
- Known gastrointestinal disease or procedure that could interfere with oral absorption or tolerance of ixazomib, including difficulty swallowing.
- Previous treatment with ixazomib.
- Known resistance to two or more classes of antiretrovirals.
Trial locations and contacts
20 sites in 1 country. Contact the study team or a site near you to ask about taking part.
20 sites in 1 country
United States20 sites
The Ponce de Leon Center CRS (Site #5802)
Atlanta, Georgia, 30308-2012
Vincent Marconi, 404-321-6111, vcmarco@emory.edu
University of Colorado Hospital CRS (Site #6101)
Aurora, Colorado, 80045
Thomas Campbell, 303-724-4929, thomas.campbell@cuanschutz.edu
Alabama CRS (Site #31788)
Birmingham, Alabama, 35222
Sonya Heath, 205-996-2371, heaths@uab.edu
Massachusetts General Hospital CRS (MGH CRS) (Site #101)
Boston, Massachusetts, 02114
Rajesh Gandhi, 617-726-3811, rgandhi@mgh.harvard.edu
Chapel Hill CRS (Site #3201)
Chapel Hill, North Carolina, 27599-7215
David Wohl, 919-843-2723, wohl@med.unc.edu
Northwestern University CRS (Site #2701)
Chicago, Illinois, 60611
Amesika Nyaku, 312-694-6856, Amesika.nyaku@northwestern.edu
Cincinnati Clinical Research Site (Site #2401)
Cincinnati, Ohio, 45267-0405
Carl Fichtenbaum, 513-584-6361, carl.fichtenbaum@uc.edu
Case Clinical Research Site (Site #2501)
Cleveland, Ohio, 44106
George Yendewa, 216-844-2298, gay7@case.edu
Ohio State University CRS (Site #2301)
Columbus, Ohio, 43210-1282
Susan Koletar, 614-293-5494, susan.koletar@osumc.edu
Houston Advancing Research Team CRS (Site #31473)
Houston, Texas, 77030
Roberto Arduino, 713-500-6731, roberto.c.arduino@uth.tmc.edu
University of California, Los Angeles CARE Center CRS (Site #601)
Los Angeles, California, 90035
Kara Chew, 310-825-0796, kchew@mednet.ucla.edu
Vanderbilt Therapeutics (VT) CRS (Site #3652)
Nashville, Tennessee, 37204
David Haas, 615-936-8594, david.haas@vumc.org
Columbia Physicians & Surgeons (P&S) CRS (Site #30329)
New York, New York, 10032
Michael Yin, 212-305-7185, mty4@cumc.columbia.edu
Penn Therapeutics CRS (Site #6201)
Philadelphia, Pennsylvania, 19104
William Short, 215-662-8693, william.short@pennmedicine.upenn.edu
University of Pittsburgh CRS (Site #1001)
Pittsburgh, Pennsylvania, 15213
Yijia Li, 412-647-7228, liy33@upmc.edu
University of Rochester Adult HIV Therapeutic Strategies Network CRS (Site #31787)
Rochester, New York, 14642
Sonal Munsiff, 585-276-7199, Sonal_Munsiff@URMC.Rochester.edu
UCSD Antiviral Research Center CRS (Site #701)
San Diego, California, 92103
Thomas Martin, 619-543-8080, thm001@health.ucsd.edu
University of California, San Francisco HIV/AIDS CRS (Site #801)
San Francisco, California, 94110
Annie Luetkemeyer, 415-502-5753, Annie.luetkemeyer@ucsf.edu
University of Washington Positive Research CRS (Site #1401)
Seattle, Washington, 98104
Rachel Bender Ignacio, 206-744-4876, rbi13@uw.edu
Whitman-Walker Institute, Inc. CRS (Site #31791)
Washington D.C., District of Columbia, 20009
Sarah Henn, 202-745-6174, shenn@whitman-walker.org
About this study
Official title: A Phase 2, Double-Blinded, Randomized, Placebo-Controlled Trial of Ixazomib to Reactivate HIV and Reduce HIV Reservoir Size
This study tests whether a medicine called ixazomib is safe for people living with HIV, and whether it can wake up HIV that is hiding in the body so the immune system and treatment can reach it.
HIV can stay hidden inside cells even when antiretroviral therapy (ART) keeps the virus under control. These hidden cells are called the HIV reservoir, and they are the reason HIV is not cured by ART alone. Laboratory research suggests ixazomib may reactivate hidden HIV and also help kill the cells that carry it. Ixazomib is already approved to treat a cancer called multiple myeloma and has been given to a smaller group of people with HIV in an earlier study.
Read more
About 45 adults with HIV that is well controlled on ART will take part. Participants are assigned by chance to take either ixazomib or a placebo - a capsule with no active medicine - one capsule by mouth once a week for a total of 25 doses. Two out of every three participants receive ixazomib and one out of three receives placebo. Neither participants nor the study staff know which one a participant is taking.
Everyone continues their own HIV treatment throughout the study.
Participation lasts about 7 months: 24 weeks of weekly capsules and 4 more weeks of follow-up after the last dose. Participants come to the clinic for about 14 visits, and take their capsule 24 to 36 hours before each visit so blood samples can show the effect of the dose.
The main purposes of the study are to evaluate whether ixazomib is safe and tolerable, and to measure whether it increases the very small amounts of HIV in the blood compared with placebo. The study also measures the size of the HIV reservoir and how the immune system responds.
Read the detailed description
A5420 is a phase 2, double-blinded, randomized, placebo-controlled trial of ixazomib in adults with HIV-1 who are virologically suppressed on antiretroviral therapy. Forty-five participants will be randomized 2:1 to ixazomib 4 mg or matching placebo, taken orally once weekly for a total of 25 doses over 24 weeks, while continuing their own suppressive ART. Randomization is stratified by sex (male/female) using permuted blocks to balance enrollment across arms. Participants are evaluated at screening, entry (week 0), and weeks 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, and 24, with a post-treatment evaluation at week 28 following a 4-week washout, for approximately 14 visits over roughly 7 months.
Study treatment is administered as a single 4 mg capsule taken with water on an empty stomach, at least 1 hour before or 2 hours after food, on the same day and at approximately the same time each week. Capsules are not broken, chewed, or opened. Doses preceding a clinic visit are taken 24 to 36 hours before that visit so that plasma and cell-associated virologic measurements capture the post-dose interval.
- Conditions
- HIV (Human Immunodeficiency Virus)
- Being tested
- Ixazomib 4 mg, Placebo
- Keywords
- HIV, AIDS, Antiretroviral Therapy
- Medical subject headings
- Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ixazomib 4 mgDrug
Also called Ninlaro, MLN9708
One Ixazomib 4 mg capsule should be taken by mouth with a full glass of water on an empty stomach at least 1 hour before or 2 hours after food once a week on the same day and approximately the same time each week
PlaceboDrug
One Placebo for Ixazomib capsule should be taken by mouth with a full glass of water on an empty stomach at least 1 hour before or 2 hours after food once a week on the same day and approximately the same time each week
| Study group | Role | What they receive |
|---|---|---|
| Ixazomib | Experimental | Ixazomib 4 mg orally once weekly for a total of 25 doses over 24 weeks. Receives: Drug: Ixazomib 4 mg |
| Placebo | Placebo comparator | Placebo for Ixazomib orally once weekly for a total of 25 doses over 24 weeks. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of Ixazomib-Treated Participants With at Least One Grade 3 or Higher Adverse Event Related to Study Treatment.
Measured: Entry (Week 0) to Week 28
Frequency of Ixazomib-Treated Participants Who Prematurely Discontinue Study Treatment for Reasons That Are Deemed Related to Study Treatment.
Measured: Entry (Week 0) to Week 24
Post-Dose Plasma HIV-1 RNA Levels Measured by Multireplicate Single-Copy Assay (SCA)
Measured: Weeks 1, 2, 3, 4, 6, 10, 12, 16, 20, and 24
Secondary outcomes (4)
Intact Proviral DNA Levels Measured by the Intact Proviral DNA Assay (IPDA)
Measured: Screening, Entry (Week 0), and Weeks 4, 24, and 28
Plasma HIV-1 RNA Levels Measured by Multireplicate Single-Copy Assay (SCA)
Measured: Screening, Entry (Week 0), and Weeks 1, 2, 3, 4, 6, 10, 12, 16, 20, and 24
Cell-Associated HIV RNA Levels
Measured: Screening, Entry (Week 0), and Weeks 1, 2, 3, 4, 6, 10, 12, 16, 20, and 24
Cell-Associated HIV RNA/DNA Ratio
Measured: Screening, Entry (Week 0), and Weeks 4, 24, and 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Oct 2026
- Study start23 Nov 2026 (estimated)
- Primary completion8 Oct 2027 (estimated)
- Study completion5 Nov 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIV (Human Immunodeficiency Virus)Studies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 45 participants (estimated)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Takeda
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07881809
- Sponsor's protocol ID
- A5420
- Status last verified
- Oct 2026
- First submitted
- 13 Oct 2026
- Last updated
- 19 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data that underlie results in the publication, after deidentification.