The Effect of Ixazomib on the Latent HIV Reservoir

NCT02946047 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 16-001938
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

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.

Conditions

Human Immunodeficiency Virus (HIV)

Keywords

Antiretroviral Therapy (ART)

Outcome Measures

Primary Outcomes (1)

• Incidence of Treatment-Emergent Adverse Events

  Number of treatment-emergent adverse events experienced by subjects as defined by NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

  7 months

Secondary Outcomes (5)

• Cell Associated HIV DNA in CD4 T Cell Subsets

  24 weeks

• Culturable HIV by Quantitative Viral Outgrowth Assay

  24 weeks

• Absolute CD4 T Cell Count

  24 weeks

• Absolute CD8 T Cell Count

  24 weeks

• CD4/CD8 Ratio

  24 weeks

Study Arms (4)

Ixazomib 1 mg

EXPERIMENTAL

Cohort A: Patients will receive ixazomib 1mg 3 times monthly for 12 weeks, then weekly for 12 weeks.

Drug: Ixazomib 1 MG

Ixazomib 2 mg

EXPERIMENTAL

Cohort B: Patients will receive ixazomib 2mg 3 times monthly for 12 weeks, then weekly for 12 weeks.

Drug: Ixazomib 2 MG

Ixazomib 3 mg

EXPERIMENTAL

Cohort C: Patients will receive ixazomib 3 mg 3 times monthly for 12 weeks, then weekly for 12 weeks.

Drug: Ixazomib 3 MG

Ixazomib 4 mg

EXPERIMENTAL

Cohort D: Patients will receive ixazomib 4mg 3 times monthly for 12 weeks, then weekly for 12 weeks.

Drug: Ixazomib 4 MG

Interventions

Ixazomib 1 MG DRUG

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.

Also known as: Ninlaro

Ixazomib 1 mg

Ixazomib 2 MG DRUG

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.

Also known as: Ninlaro

Ixazomib 2 mg

Ixazomib 3 MG DRUG

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.

Also known as: Ninlaro

Ixazomib 3 mg

Ixazomib 4 MG DRUG

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.

Also known as: Ninlaro

Ixazomib 4 mg

Eligibility Criteria

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

You may qualify if:

• 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,
• 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.)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Mayo Clinic: lead
• Takeda: collaborator

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Related Links

• Mayo Clinic Clinical Trials

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

Results Point of Contact

• Title: Dr. Nathan Cummins
• Organization: Mayo Clinic

Cummins.Nathan@mayo.edu

507-284-3747

Study Officials

• Nathan Cummins, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: October 24, 2016
• First Posted: October 26, 2016
• Study Start: March 20, 2017
• Primary Completion: August 19, 2019
• Study Completion: August 19, 2019
• Last Updated: January 6, 2022
• Results First Posted: January 6, 2022

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)