A Clinical Study of Ixazomib to Reactivate HIV and Reduce HIV Reservoir Size

NCT07881809 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: A5420
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 20

Brief 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. 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. 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.

Conditions

HIV (Human Immunodeficiency Virus)

Keywords

HIV; AIDS; Antiretroviral Therapy

Outcome Measures

Primary Outcomes (3)

• Proportion of Ixazomib-Treated Participants With at Least One Grade 3 or Higher Adverse Event Related to Study Treatment.

  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.

  Entry (Week 0) to Week 24

• Post-Dose Plasma HIV-1 RNA Levels Measured by Multireplicate Single-Copy Assay (SCA)

  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)

  Screening, Entry (Week 0), and Weeks 4, 24, and 28

• Plasma HIV-1 RNA Levels Measured by Multireplicate Single-Copy Assay (SCA)

  Screening, Entry (Week 0), and Weeks 1, 2, 3, 4, 6, 10, 12, 16, 20, and 24

• Cell-Associated HIV RNA Levels

  Screening, Entry (Week 0), and Weeks 1, 2, 3, 4, 6, 10, 12, 16, 20, and 24

• Cell-Associated HIV RNA/DNA Ratio

  Screening, Entry (Week 0), and Weeks 4, 24, and 28

Study Arms (2)

Ixazomib

EXPERIMENTAL

Ixazomib 4 mg orally once weekly for a total of 25 doses over 24 weeks.

Drug: Ixazomib 4 mg

Placebo

PLACEBO COMPARATOR

Placebo for Ixazomib orally once weekly for a total of 25 doses over 24 weeks.

Drug: Placebo

Interventions

Ixazomib 4 mg DRUG

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

Also known as: Ninlaro, MLN9708

Ixazomib

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• History of an HIV-associated malignancy, including Kaposi sarcoma or lymphoma of any type, treated with systemic chemotherapy or immunotherapy.
• 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.

Sponsors & Collaborators

• Takeda: collaborator
• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (20)

Alabama CRS (Site #31788)

Birmingham, Alabama, 35222, United States

Location

University of California, Los Angeles CARE Center CRS (Site #601)

Los Angeles, California, 90035, United States

Location

UCSD Antiviral Research Center CRS (Site #701)

San Diego, California, 92103, United States

Location

University of California, San Francisco HIV/AIDS CRS (Site #801)

San Francisco, California, 94110, United States

Location

University of Colorado Hospital CRS (Site #6101)

Aurora, Colorado, 80045, United States

Location

Whitman-Walker Institute, Inc. CRS (Site #31791)

Washington D.C., District of Columbia, 20009, United States

Location

The Ponce de Leon Center CRS (Site #5802)

Atlanta, Georgia, 30308-2012, United States

Location

Northwestern University CRS (Site #2701)

Chicago, Illinois, 60611, United States

Location

Massachusetts General Hospital CRS (MGH CRS) (Site #101)

Boston, Massachusetts, 02114, United States

Location

Columbia Physicians & Surgeons (P&S) CRS (Site #30329)

New York, New York, 10032, United States

Location

University of Rochester Adult HIV Therapeutic Strategies Network CRS (Site #31787)

Rochester, New York, 14642, United States

Location

Chapel Hill CRS (Site #3201)

Chapel Hill, North Carolina, 27599-7215, United States

Location

Cincinnati Clinical Research Site (Site #2401)

Cincinnati, Ohio, 45267-0405, United States

Location

Case Clinical Research Site (Site #2501)

Cleveland, Ohio, 44106, United States

Location

Ohio State University CRS (Site #2301)

Columbus, Ohio, 43210-1282, United States

Location

Penn Therapeutics CRS (Site #6201)

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh CRS (Site #1001)

Pittsburgh, Pennsylvania, 15213, United States

Location

Vanderbilt Therapeutics (VT) CRS (Site #3652)

Nashville, Tennessee, 37204, United States

Location

Houston Advancing Research Team CRS (Site #31473)

Houston, Texas, 77030, United States

Location

University of Washington Positive Research CRS (Site #1401)

Seattle, Washington, 98104, United States

Location

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

ixazomib

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 13, 2026
• First Posted: October 19, 2026
• Study Start (Estimated): November 23, 2026
• Primary Completion (Estimated): October 8, 2027
• Study Completion (Estimated): November 5, 2027
• Last Updated: October 19, 2026

Record last verified: 2026-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 3 months following publication and available throughout period of funding of the Advancing Clinical Therapeutics Globally (ACTG) by NIH
• Access Criteria: With whom? Researchers who provide a methodologically sound proposal for use of the data that is approved by the ACTG. For what types of analyses? To achieve aims in the proposal approved by the ACTG. By what mechanism will data be made available? Researchers may submit a request for access to data using the ACTG "Data Request" form at: https://actgnetwork.org/submit-a-proposal/. Researchers of approved proposals will need to sign an ACTG Data Use Agreement before receiving the data.

Locations

US (20)