Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

The Effect of Ixazomib on the Latent HIV Reservoir

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02946047
Recruitment Status : Completed
First Posted : October 26, 2016
Results First Posted : January 6, 2022
Last Update Posted : January 6, 2022
Sponsor:
Collaborator:
Takeda
Information provided by (Responsible Party):
Nathan W. Cummins, M.D., Mayo Clinic

Brief Summary:
The primary purpose of the trial is to determine the safety and tolerability of ixazomib in HIV infected patients on antiretroviral therapy. The secondary purpose is to determine the effect of ixazomib on the size of the HIV reservoir.

Condition or disease Intervention/treatment Phase
Human Immunodeficiency Virus (HIV) Drug: Ixazomib 1 MG Drug: Ixazomib 2 MG Drug: Ixazomib 3 MG Drug: Ixazomib 4 MG Phase 1 Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 17 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pilot Study of Ixazomib to Reduce the Number of HIV DNA Positive Lymphoid Cells
Actual Study Start Date : March 20, 2017
Actual Primary Completion Date : August 19, 2019
Actual Study Completion Date : August 19, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: Ixazomib 1 mg
Cohort A: Patients will receive ixazomib 1mg 3 times monthly for 12 weeks, then weekly for 12 weeks.
Drug: Ixazomib 1 MG
1 mg on days 1, 8 and 15 for three 28 days cycles, then be reviewed by DSMB and based upon their recommendation patients will receive ixazomib once weekly for 12 weeks or ixazomib 1 mg on days 1, 8 and 15 for three 28 days cycles. Visits 3-15 will have a window of ± 3 days.
Other Name: Ninlaro

Experimental: Ixazomib 2 mg
Cohort B: Patients will receive ixazomib 2mg 3 times monthly for 12 weeks, then weekly for 12 weeks.
Drug: Ixazomib 2 MG
2mg on days 1, 8 and 15 for three 28 days cycles, then be reviewed by DSMB and based upon their recommendation patients will receive ixazomib once weekly for 12 weeks or ixazomib 2 mg on days 1, 8 and 15 for three 28 days cycles. Visits 3-15 will have a window of ± 3 days.
Other Name: Ninlaro

Experimental: Ixazomib 3 mg
Cohort C: Patients will receive ixazomib 3 mg 3 times monthly for 12 weeks, then weekly for 12 weeks.
Drug: Ixazomib 3 MG
3 mg on days 1, 8 and 15 for three 28 days cycles, then be reviewed by DSMB and based upon their recommendation patients will receive ixazomib once weekly for 12 weeks or ixazomib 3 mg on days 1, 8 and 15 for three 28 days cycles. Visits 3-15 will have a window of ± 3 days.
Other Name: Ninlaro

Experimental: Ixazomib 4 mg
Cohort D: Patients will receive ixazomib 4mg 3 times monthly for 12 weeks, then weekly for 12 weeks.
Drug: Ixazomib 4 MG
4 mg on days 1, 8 and 15 for three 28 days cycles, then be reviewed by DSMB and based upon their recommendation patients will receive ixazomib once weekly for 12 weeks or ixazomib 4 mg on days 1, 8 and 15 for three 28 days cycles. Visits 3-15 will have a window of ± 3 days.
Other Name: Ninlaro




Primary Outcome Measures :
  1. Incidence of Treatment-Emergent Adverse Events [ Time Frame: 7 months ]
    Number of treatment-emergent adverse events experienced by subjects as defined by NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0


Secondary Outcome Measures :
  1. Cell Associated HIV DNA in CD4 T Cell Subsets [ Time Frame: 24 weeks ]
    HIV copies per million CD4 T cells

  2. Culturable HIV by Quantitative Viral Outgrowth Assay [ Time Frame: 24 weeks ]
    Infectious units per million CD4 T cells

  3. Absolute CD4 T Cell Count [ Time Frame: 24 weeks ]
    Cells per microliter

  4. Absolute CD8 T Cell Count [ Time Frame: 24 weeks ]
    Cells per microliter

  5. CD4/CD8 Ratio [ Time Frame: 24 weeks ]
    CD4/CD8 T cell count ratio



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • The following laboratory values obtained <=14 days prior to registration.
  • ANC ≥ LLN (lower limit of normal) and ≤ULN (upper limit of normal), Hgb ≥ LLN and ≤ULN, PLT ≥ LLN and ≤ULN
  • Total bilirubin ≤ULN and the direct bilirubin must be ≤ ULN; AST <1.5 x ULN and ALT <1.5 x ULN
  • Creatinine <2.0 x ULN and an estimated creatinine clearance > 60 ml/min
  • HIV infection with suppressed viral replication on at least 3 active drug ART for at least 6 months
  • Suppressed viral replication is defined by plasma HIV viral load <20copies/mL.
  • Patient must have HIV viral load <20 copies/ml on two occasions at least 3 months apart.
  • In the opinion of the treating physician, patients must have available other regimens likely to suppress HIV should their current regimen fail.
  • Male or female patients age >=18 years
  • A plasma HIV RNA viral load demonstrating a measure of <20 copies/mL within 30 days prior to study initiation.
  • CD4 count >500 cells/mm3 within 30 days prior to study enrollment
  • Females must have a negative pregnancy test prior to receiving the 1st dose of ixazomib and be postmenopausal for at least 1 year before the screen visit, or surgically sterile,
  • Male patients, even if surgically sterilized (ie, status post-vasectomy), must agree to one of the following:

    • Agree to practice effective barrier contraception AND a second method of contraception for female partners of childbearing potential during the entire study treatment period and through 90 days after the last dose of ixazomib,
    • OR
    • Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception.)
    • AND
    • Agree to forego sperm donation for the same period as above.

Exclusion Criteria:

  • The following laboratory values obtained <=14 days prior to registration.

    • ANC < LLN and >ULN, Hgb < LLN and >ULN, PLT < LLN and >ULN
    • Total bilirubin >ULN or the direct bilirubin is > ULN; AST >1.5 x ULN or AST >1.5 x ULN
    • Creatinine >=2.0 x ULN or an estimated creatinine clearance <=60mL/min
  • Diagnosed and treated for a malignancy within 5 years before randomization, or previously diagnosed with a malignancy and have any evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection
  • Any infection except HIV (excluding benign conditions that is unlikely to be affected or modulated by treatment with ixazomib, e.g. stye or furuncle), or treatment with anti-infective agents within 14 days of enrollment.
  • Pregnant women
  • Women of childbearing potential and Nursing women
  • Men who are unwilling to use a condom (even if they have undergone a prior vasectomy) while having intercourse, while taking the drug and for 90 days after stopping ixazomib.
  • Any history of peripheral neuropathy, or peripheral neuropathy detected during the screening period.
  • Major surgery within 14 days before study registration
  • Systemic treatment with strong CYP3A inducers (rifampin, rifapentine, rifabutin,carbamazepine, phenytoin, phenobarbital), or use of St. John's wort.
  • Evidence of current uncontrolled cardiovascular conditions, including serious cardiac arrhythmias, congestive heart failure, angina, or myocardial infarction within the past 6 months.
  • QTc > 450 milliseconds (msec) for men and >470 milliseconds for women (83) on a 12 lead ECG obtained during the Screening period.
  • Known hepatitis B DNA positive status and/or HBsAg positive and/or HBeAg positive, or active hepatitis C replication (HCV RNA positive) or currently on hepatitis C treatment.
  • Known history of cirrhosis or active liver inflammation, including "fatty liver" or non-alcohol steatohepatitis (NASH).
  • Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
  • Known allergy to any of the study medications, their analogues or excipients in the various formulations.
  • Any other recent or concurrent medical condition that, in the Investigator's opinion, would impose any risk to the patient
  • Known GI disease or GI procedure that could interfere with the oral absorption or tolerance of ixazomib including difficulty swallowing.
  • Participation in other clinical trials, including those with other investigational agents not included in this trial, within 30 days of the start of this trial and throughout the duration of this trial.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02946047


Locations
Layout table for location information
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
Takeda
Investigators
Layout table for investigator information
Principal Investigator: Nathan Cummins, MD Mayo Clinic
  Study Documents (Full-Text)

Documents provided by Nathan W. Cummins, M.D., Mayo Clinic:
Additional Information:
Layout table for additonal information
Responsible Party: Nathan W. Cummins, M.D., MD, Mayo Clinic
ClinicalTrials.gov Identifier: NCT02946047    
Other Study ID Numbers: 16-001938
First Posted: October 26, 2016    Key Record Dates
Results First Posted: January 6, 2022
Last Update Posted: January 6, 2022
Last Verified: December 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Nathan W. Cummins, M.D., Mayo Clinic:
Antiretroviral Therapy (ART)
Additional relevant MeSH terms:
Layout table for MeSH terms
Acquired Immunodeficiency Syndrome
HIV Infections
Immunologic Deficiency Syndromes
Immune System Diseases
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
Ixazomib
Glycine
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Glycine Agents
Neurotransmitter Agents
Physiological Effects of Drugs