A Clinical Study of Ixazomib to Reactivate HIV and Reduce HIV Reservoir Size
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.
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.
Studieoversigt
Status
Status
Betingelser
Betingelser
Intervention / Behandling
Intervention / Behandling
Detaljeret beskrivelse
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.
Undersøgelsestype
Undersøgelsestype
Tilmelding (Anslået)
Tilmelding
Fase
Fase
- Fase 2
Kontakter og lokationer
Studiesteder
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Alabama
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Birmingham, Alabama, Forenede Stater, 35222
- Alabama CRS (Site #31788)
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Kontakt:
- Sonya Heath
- Telefonnummer: 205-996-2371
- E-mail: heaths@uab.edu
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California
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Los Angeles, California, Forenede Stater, 90035
- University of California, Los Angeles CARE Center CRS (Site #601)
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Kontakt:
- Kara Chew
- Telefonnummer: 310-825-0796
- E-mail: kchew@mednet.ucla.edu
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San Diego, California, Forenede Stater, 92103
- UCSD Antiviral Research Center CRS (Site #701)
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Kontakt:
- Steven Hendrickx
- Telefonnummer: 619-543-6968
- E-mail: smhendrickx@health.ucsd.edu
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San Francisco, California, Forenede Stater, 94110
- University of California, San Francisco HIV/AIDS CRS (Site #801)
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Kontakt:
- Annie Luetkemeyer
- Telefonnummer: 415-502-5753
- E-mail: Annie.luetkemeyer@ucsf.edu
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Colorado
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Aurora, Colorado, Forenede Stater, 80045
- University of Colorado Hospital CRS (Site #6101)
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Kontakt:
- Nicola Haakonsen
- Telefonnummer: 303-724-0708
- E-mail: Nicola.haakonsen@cuanschutz.edu
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District of Columbia
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Washington D.C., District of Columbia, Forenede Stater, 20009
- Whitman-Walker Institute, Inc. CRS (Site #31791)
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Kontakt:
- Sarah Henn
- Telefonnummer: 202-745-6174
- E-mail: shenn@whitman-walker.org
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Georgia
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Atlanta, Georgia, Forenede Stater, 30308-2012
- The Ponce de Leon Center CRS (Site #5802)
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Kontakt:
- Vincent Marconi
- Telefonnummer: 404-321-6111
- E-mail: vcmarco@emory.edu
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Illinois
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Chicago, Illinois, Forenede Stater, 60611
- Northwestern University CRS (Site #2701)
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Kontakt:
- Amesika Nyaku
- Telefonnummer: 312-694-6856
- E-mail: Amesika.nyaku@northwestern.edu
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Massachusetts
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Boston, Massachusetts, Forenede Stater, 02114
- Massachusetts General Hospital CRS (MGH CRS) (Site #101)
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Kontakt:
- Rajesh Gandhi
- Telefonnummer: 617-726-3811
- E-mail: rgandhi@mgh.harvard.edu
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New York
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New York, New York, Forenede Stater, 10032
- Columbia Physicians & Surgeons (P&S) CRS (Site #30329)
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Kontakt:
- Michael Yin
- Telefonnummer: 212-305-7185
- E-mail: mty4@cumc.columbia.edu
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Rochester, New York, Forenede Stater, 14642
- University of Rochester Adult HIV Therapeutic Strategies Network CRS (Site #31787)
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Kontakt:
- Sonal Munsiff
- Telefonnummer: 585-276-7199
- E-mail: Sonal_Munsiff@URMC.Rochester.edu
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North Carolina
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Chapel Hill, North Carolina, Forenede Stater, 27599-7215
- Chapel Hill CRS (Site #3201)
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Kontakt:
- David Wohl
- Telefonnummer: 919-843-2723
- E-mail: wohl@med.unc.edu
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Ohio
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Cincinnati, Ohio, Forenede Stater, 45267-0405
- Cincinnati Clinical Research Site (Site #2401)
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Kontakt:
- Carl Fichtenbaum
- Telefonnummer: 513-584-6361
- E-mail: carl.fichtenbaum@uc.edu
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Cleveland, Ohio, Forenede Stater, 44106
- Case Clinical Research Site (Site #2501)
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Kontakt:
- George Yendewa
- Telefonnummer: 216-844-2298
- E-mail: gay7@case.edu
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Columbus, Ohio, Forenede Stater, 43210-1282
- Ohio State University CRS (Site #2301)
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Kontakt:
- Susan Koletar
- Telefonnummer: 614-293-5494
- E-mail: susan.koletar@osumc.edu
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Pennsylvania
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Philadelphia, Pennsylvania, Forenede Stater, 19104
- Penn Therapeutics CRS (Site #6201)
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Kontakt:
- William Short
- Telefonnummer: 215-662-8693
- E-mail: william.short@pennmedicine.upenn.edu
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Pittsburgh, Pennsylvania, Forenede Stater, 15213
- University of Pittsburgh CRS (Site #1001)
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Kontakt:
- Yijia Li
- Telefonnummer: 412-647-7228
- E-mail: liy33@upmc.edu
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Tennessee
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Nashville, Tennessee, Forenede Stater, 37204
- Vanderbilt Therapeutics (VT) CRS (Site #3652)
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Kontakt:
- David Haas
- Telefonnummer: 615-936-8594
- E-mail: david.haas@vumc.org
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Texas
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Houston, Texas, Forenede Stater, 77030
- Houston Advancing Research Team CRS (Site #31473)
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Kontakt:
- Roberto Arduino
- Telefonnummer: 713-500-6731
- E-mail: roberto.c.arduino@uth.tmc.edu
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Washington
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Seattle, Washington, Forenede Stater, 98104
- University of Washington Positive Research CRS (Site #1401)
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Kontakt:
- Rachel Bender Ignacio
- Telefonnummer: 206-744-4876
- E-mail: rbi13@uw.edu
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Deltagelseskriterier
Berettigelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
- 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.
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Firedobbelt
Antal våben
Våben og indgreb
Deltagergruppe / ArmDeltagergruppe / Arm |
Intervention / BehandlingIntervention / Behandling |
|---|---|
|
Eksperimentel: Ixazomib
Ixazomib 4 mg orally once weekly for a total of 25 doses over 24 weeks. |
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
Andre navne:
|
|
Placebo komparator: Placebo
Placebo for Ixazomib orally once weekly for a total of 25 doses over 24 weeks. |
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 |
Hvad måler undersøgelsen?
Primære resultatmål
Primære resultatmål
Resultatmål |
Tidsramme |
|---|---|
|
Proportion of Ixazomib-Treated Participants With at Least One Grade 3 or Higher Adverse Event Related to Study Treatment.
Tidsramme: Entry (Week 0) to Week 28
|
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.
Tidsramme: Entry (Week 0) to Week 24
|
Entry (Week 0) to Week 24
|
|
Post-Dose Plasma HIV-1 RNA Levels Measured by Multireplicate Single-Copy Assay (SCA)
Tidsramme: Weeks 1, 2, 3, 4, 6, 10, 12, 16, 20, and 24
|
Weeks 1, 2, 3, 4, 6, 10, 12, 16, 20, and 24
|
Sekundære resultatmål
Sekundære resultatmål
Resultatmål |
Tidsramme |
|---|---|
|
Intact Proviral DNA Levels Measured by the Intact Proviral DNA Assay (IPDA)
Tidsramme: Screening, Entry (Week 0), and Weeks 4, 24, and 28
|
Screening, Entry (Week 0), and Weeks 4, 24, and 28
|
|
Plasma HIV-1 RNA Levels Measured by Multireplicate Single-Copy Assay (SCA)
Tidsramme: Screening, Entry (Week 0), and Weeks 1, 2, 3, 4, 6, 10, 12, 16, 20, and 24
|
Screening, Entry (Week 0), and Weeks 1, 2, 3, 4, 6, 10, 12, 16, 20, and 24
|
|
Cell-Associated HIV RNA Levels
Tidsramme: Screening, Entry (Week 0), and Weeks 1, 2, 3, 4, 6, 10, 12, 16, 20, and 24
|
Screening, Entry (Week 0), and Weeks 1, 2, 3, 4, 6, 10, 12, 16, 20, and 24
|
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Cell-Associated HIV RNA/DNA Ratio
Tidsramme: Screening, Entry (Week 0), and Weeks 4, 24, and 28
|
Screening, Entry (Week 0), and Weeks 4, 24, and 28
|
Samarbejdspartnere og efterforskere
Sponsor
Sponsor
Samarbejdspartnere
Samarbejdspartnere
Datoer for undersøgelser
Studer store datoer
Studiestart (Anslået)
Studiestart
Primær færdiggørelse (Anslået)
Primær færdiggørelse
Studieafslutning (Anslået)
Studieafslutning
Datoer for studieregistrering
Først indsendt
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først indsendt, der opfyldte QC-kriterier
Først opslået (Faktiske)
Først opslået
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering sendt
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Yderligere relevante MeSH-vilkår
- Blodbårne infektioner
- Urogenitale sygdomme
- Genitale sygdomme
- Sygdomme i immunsystemet
- Infektioner
- RNA-virusinfektioner
- Virussygdomme
- Overførbare sygdomme
- Seksuelt overførte sygdomme, virale
- Seksuelt overførte sygdomme
- Lentivirus infektioner
- Retroviridae infektioner
- Immunologiske mangelsyndromer
- Langsomme virussygdomme
- HIV-infektioner
- Erhvervet immundefektsyndrom
- Ixazomib
Andre undersøgelses-id-numre
Andre undersøgelses-id-numre
- A5420
- 39030 (Anden identifikator: DAIDS Document ID)
Plan for individuelle deltagerdata (IPD)
Planlægger du at dele individuelle deltagerdata (IPD)?
IPD-planbeskrivelse
Individual participant data that underlie results in the publication, after deidentification.
IPD-delingstidsramme
Beginning 3 months following publication and available throughout period of funding of the Advancing Clinical Therapeutics Globally (ACTG) by NIH
IPD-delingsadgangskriterier
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.
IPD-deling Understøttende informationstype
- STUDY_PROTOCOL
- SAP
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