Kidney DiseasesPhase 2IXADESNCT03213158
Ixazomib for Desensitization
A Phase 2 study testing Ixazomib Oral Capsule in people with Kidney Diseases and End Stage Renal Disease, run by University of Wisconsin, Madison at 1 site in United States.
Trial summary
The purpose of this research study is to find out how well ixazomib (the study drug) works to desensitize highly sensitized kidney transplant recipients. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Kidney Diseases, End Stage Renal Disease
- What is being tested?
- Ixazomib Oral Capsule
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Sep 2017to 16 Apr 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Male or female patients 18-70 years of age.
- Able to provide informed consent.
- Female patients who are postmenopausal for at least 1 year before the screening visit, or are surgically sterile, or If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form through 30 days after the last dose of study drug, 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.)
- Male patients, even if surgically sterilized (ie, status post-vasectomy), must agree to one of the following: Agree to practice effective barrier contraception during the entire study treatment period and through 30 days after the last dose of study drug, 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.)
- Patients must be highly sensitized with a cPRA ≥ 80%
- Be active on the waitlist for kidney transplantation > 24 months to confirm their inability to receive a deceased donor transplant because of their sensitization status.
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- Patients must meet the following clinical laboratory criteria:
- Absolute neutrophil count (ANC) ≥ 1,000/mm3 and platelet count ≥ 75,000/mm3. Platelet transfusions to help patients meet eligibility criteria are not allowed within 3 days before study enrollment.
- Hemoglobin higher than 6 g/dL
- Total bilirubin ≤ 1.5 x the upper limit of the normal range (ULN).
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN.
Who cannot join
- Female patients who are lactating or have a positive serum pregnancy test during the screening period
- Major surgery requiring hospitalization within 6 months before enrollment
- Infection requiring systemic antibiotic therapy or other serious infection within 14 days before study enrollment
- Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months
- Systemic treatment, within 14 days before the first dose of ixazomib, with strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of St. John's wort
- Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol
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- Inability to take oral medication
- Diagnosed or treated for another malignancy within 2 years before study enrollment or previously diagnosed with another 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
- Grade 2 or greater peripheral neuropathy according to NCI Common Terminology Criteria for Adverse Events (CTCAE)
- Participation in other interventional clinical trials, including those with other investigational agents not included in this trial, within 6 months of the start of this trial and throughout the duration of this trial
- Patients that have previously been treated with ixazomib, or participated in a study with ixazomib whether treated with ixazomib or not
- Active or treated infection for HIV, HCV or HBV
- History of Liver cirrhosis, biopsy confirmed
- Elevated transaminases (greater than 3 times the upper limit of normal)
- Known hypersensitivity to ixazomib
- Active substance abuse by self-report or medical record
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, 53792
About this study
Official title: Ixazomib for Desensitization in Kidney Transplantation
The purpose of this research study is to find out how well ixazomib (the study drug) works to desensitize highly sensitized kidney transplant recipients.
Read the detailed description
This is a pilot exploratory, proof of concept, open-label, single-center phase II investigator initiated clinical trial entitled IXAzomib for DESensitization (IXADES). The purpose of the study is (1) to examine the safety and efficacy of ixazomib for desensitization of highly sensitized kidney transplant candidates and (2) to conduct mechanistic studies to address the role of HLA and non-HLA antibodies, T and B cell phenotypes, and BAFF/APRIL in immune monitoring of sensitized kidney transplant candidates.
Specific Aim 1. To determine the safety and efficacy of ixazomib as a desensitization strategy. There is currently no effective desensitization strategy for highly sensitized patients defined as calculated Panel of Reactive Antibodies (cPRA) ≥ 80%. For this study, 10 highly sensitized kidney transplant candidates on the waitlist for more than 24 months will receive ixazomib 3 mg (and dexamethasone 20 mg) on days 1, 8, and 15 of a 28 cycle for 12 months. The primary objective is to evaluate the safety (distal neuropathy, thrombocytopenia, and gastrointestinal symptoms) and efficacy (decline in cPRA > 20%) of ixazomib. The secondary efficacy endpoint is transplantation rate within 12 months of therapy.
Specific Aim 2. Identify immune indices which predict the course of disease and/or response to treatment in highly sensitized patients. Mechanistic studies will use bone marrow and blood obtained from subjects in Aim 1 to determine the effect of treatment on immune regulation and reconstitution after therapy. Since the bone marrow microenvironment produces BAFF/APRIL and supports plasma cell maturation,the effect of therapy on the generation of BAFF/APRIL will be determined by bone marrow mesenchymal stem cells and the survival of bone marrow-derived plasma cells after desensitization. Specifically it's proposed to:
- Identify if bone marrow plasma cells, IgG subsets, and levels including free light chains, and circulating BAFF/APRIL predict outcomes.
- Determine if treatment is effective in downregulating circulating BAFF/APRIL and anti-HLA, endothelin-1 type A receptor (ETAR), angiotensin type 1 receptor (AT1R), and complement fixing C1q antibodies.
- Conditions
- Kidney Diseases, End Stage Renal Disease
- Being tested
- Ixazomib Oral Capsule
- Medical subject headings
- Kidney Diseases, Kidney Failure, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ixazomib Oral CapsuleDrug
Highly sensitized kidney transplant candidates on the waitlist for more than 24 months will receive ixazomib 3 mg (and dexamethasone 20 mg) on days 1, 8, and 15 of a 28 cycle. Patients will take ixazomib and dexamethasone for twelve (12) 28-day cycles.
| Study group | Role | What they receive |
|---|---|---|
| Highly sensitized kidney transplant candidates | Experimental | The study population will include all highly sensitized kidney transplant candidates on the waitlist for more than 24 months at University of Wisconsin. Receives: Drug: Ixazomib Oral Capsule |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy of Ixazomib: Percentage of Participants With > 20 Percent Decline in Calculated Panel Reactive Antibody (cPRA)
Measured: up to 12 months
Efficacy of Ixazomib: Percentage of Participants Received Successful Kidney Transplantation Within 12 Months
Measured: up to 12 months
Secondary outcomes (7)
Safety of Ixazomib as Assesses by Percentage of Participants With Cardiovascular Complications Within 12 Months
Measured: up to 12 months
Safety of Ixazomib as Assesses by Percentage of Participants With Hematological Complications Within 12 Months
Hematological complications include leucopenia, anemia, and thrombocytopenia
Measured: up to 12 months
Safety of Ixazomib as Assesses by Percentage of Participants With Malignancies Within 12 Months
Measured: up to 12 months
Safety of Ixazomib as Assesses by Percentage of Participants With Gastrointestinal Symptoms Within 12 Months
Measured: up to 12 months
Safety of Ixazomib as Assesses by Percentage of Participants Caught Infection Within 12 Months
Measured: up to 12 months
Safety of Ixazomib as Assesses by Percentage of Participants With Thrombocytopenia Within 12 Months
Measured: up to 12 months
Safety of Ixazomib: as Assesses by Percentage of Participants With Distal Neuropathy Within 12 Months
Measured: up to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2017
- Study start15 Sep 2017
- Primary completion16 Apr 2021
- Study completion16 Apr 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Kidney DiseasesStudies of the same condition, open and under way.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Wisconsin, Madison
- Sponsor type
- University, hospital or other
- Collaborators
- Millennium Pharmaceuticals, Inc.
- Responsible party
- Sponsor
- Investigators
- Arjang Djamali, MD, MS, FASN, Principal investigator, University of Wisconsin, Madison
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03213158
- Sponsor's protocol ID
- 2017-0429
- Other IDs
- A534280, SMPH\MEDICINE\NEPHROLOGY, Protocol ver 3June 2019
- Acronym
- IXADES
- Status last verified
- May 2022
- First submitted
- 26 Apr 2017
- Last updated
- 1 Jun 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Wilson N, Reese S, Ptak L, Aziz F, Parajuli S, Jucaud V, Denham S, Mishra A, Cascalho M, Platt JL, Hematti P, Djamali A. Ixazomib for Desensitization (IXADES) in Highly Sensitized Kidney Transplant Candidates: A Phase II Clinical Trial. Kidney360. 2023 Jun 1;4(6):e796-e808. doi: 10.34067/KID.0000000000000113. Epub 2023 Mar 23.
PubMed 36951387
Study at a glance
From the registry record, last updated by the sponsor on 1 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ixazomib for Desensitization in Kidney Transplantation
- ClinicalTrials.gov ID
- NCT03213158
- Acronym / sponsor ID
- IXADES / 2017-0429
- Conditions
- Kidney Diseases, End Stage Renal Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- University of Wisconsin, MadisonUniversity, hospital or other
- Collaborators
- Millennium Pharmaceuticals, Inc.
- Study start
- 15 Sep 2017 (actual)
- Primary completion
- 16 Apr 2021 (actual)
- Study completion
- 16 Apr 2021 (actual)
- First posted
- 11 Jul 2017 (actual)
- Results
- Posted 11 May 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this research study is to find out how well ixazomib (the study drug) works to desensitize highly sensitized kidney transplant recipients.
Detailed description
This is a pilot exploratory, proof of concept, open-label, single-center phase II investigator initiated clinical trial entitled IXAzomib for DESensitization (IXADES). The purpose of the study is (1) to examine the safety and efficacy of ixazomib for desensitization of highly sensitized kidney transplant candidates and (2) to conduct mechanistic studies to address the role of HLA and non-HLA antibodies, T and B cell phenotypes, and BAFF/APRIL in immune monitoring of sensitized kidney transplant candidates.
Specific Aim 1. To determine the safety and efficacy of ixazomib as a desensitization strategy. There is currently no effective desensitization strategy for highly sensitized patients defined as calculated Panel of Reactive Antibodies (cPRA) ≥ 80%. For this study, 10 highly sensitized kidney transplant candidates on the waitlist for more than 24 months will receive ixazomib 3 mg (and dexamethasone 20 mg) on days 1, 8, and 15 of a 28 cycle for 12 months. The primary objective is to evaluate the safety (distal neuropathy, thrombocytopenia, and gastrointestinal symptoms) and efficacy (decline in cPRA > 20%) of ixazomib. The secondary efficacy endpoint is transplantation rate within 12 months of therapy.
Specific Aim 2. Identify immune indices which predict the course of disease and/or response to treatment in highly sensitized patients. Mechanistic studies will use bone marrow and blood obtained from subjects in Aim 1 to determine the effect of treatment on immune regulation and reconstitution after therapy. Since the bone marrow microenvironment produces BAFF/APRIL and supports plasma cell maturation,the effect of therapy on the generation of BAFF/APRIL will be determined by bone marrow mesenchymal stem cells and the survival of bone marrow-derived plasma cells after desensitization. Specifically it's proposed to:
- Identify if bone marrow plasma cells, IgG subsets, and levels including free light chains, and circulating BAFF/APRIL predict outcomes.
- Determine if treatment is effective in downregulating circulating BAFF/APRIL and anti-HLA, endothelin-1 type A receptor (ETAR), angiotensin type 1 receptor (AT1R), and complement fixing C1q antibodies.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Highly sensitized kidney transplant candidates | Experimental | Drug: Ixazomib Oral CapsuleThe study population will include all highly sensitized kidney transplant candidates on the waitlist for more than 24 months at University of Wisconsin. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Male or female patients 18-70 years of age.
- Able to provide informed consent.
- Female patients who are postmenopausal for at least 1 year before the screening visit, or are surgically sterile, or If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form through 30 days after the last dose of study drug, 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.)
- Male patients, even if surgically sterilized (ie, status post-vasectomy), must agree to one of the following: Agree to practice effective barrier contraception during the entire study treatment period and through 30 days after the last dose of study drug, 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.)
- Patients must be highly sensitized with a cPRA ≥ 80%
Key exclusion criteria (16 listed)
- Female patients who are lactating or have a positive serum pregnancy test during the screening period
- Major surgery requiring hospitalization within 6 months before enrollment
- Infection requiring systemic antibiotic therapy or other serious infection within 14 days before study enrollment
- Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months
- Systemic treatment, within 14 days before the first dose of ixazomib, with strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of St. John's wort
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ixazomib Oral CapsuleHighly sensitized kidney transplant candidates on the waitlist for more than 24 months will receive ixazomib 3 mg (and dexamethasone 20 mg) on days 1, 8, and 15 of a 28 cycle. Patients will take ixazomib and dexamethasone for twelve (12) 28-day cycles. | Drug | Highly sensitized kidney transplant candidates |
Primary outcome
Efficacy of Ixazomib: Percentage of Participants With > 20 Percent Decline in Calculated Panel Reactive Antibody (cPRA)
Time frame: up to 12 months
Efficacy of Ixazomib: Percentage of Participants Received Successful Kidney Transplantation Within 12 Months
Time frame: up to 12 months
7 secondary outcomes
Safety of Ixazomib as Assesses by Percentage of Participants With Cardiovascular Complications Within 12 Months
Time frame: up to 12 months
Safety of Ixazomib as Assesses by Percentage of Participants With Hematological Complications Within 12 Months
Time frame: up to 12 months
Safety of Ixazomib as Assesses by Percentage of Participants With Malignancies Within 12 Months
Time frame: up to 12 months
Safety of Ixazomib as Assesses by Percentage of Participants With Gastrointestinal Symptoms Within 12 Months
Time frame: up to 12 months
Safety of Ixazomib as Assesses by Percentage of Participants Caught Infection Within 12 Months
Time frame: up to 12 months
Safety of Ixazomib as Assesses by Percentage of Participants With Thrombocytopenia Within 12 Months
Time frame: up to 12 months
Safety of Ixazomib: as Assesses by Percentage of Participants With Distal Neuropathy Within 12 Months
Time frame: up to 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jun 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36951387Wilson N, Reese S, Ptak L, Aziz F, Parajuli S, Jucaud V, Denham S, Mishra A, Cascalho M, Platt JL, Hematti P, Djamali A. Ixazomib for Desensitization (IXADES) in Highly Sensitized Kidney Transplant Candidates: A Phase II Clinical Trial. Kidney360. 2023 Jun 1;4(6):e796-e808. doi: 10.34067/KID.0000000000000113. Epub 2023 Mar 23.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Arjang Djamali, MD, MS, FASN principal investigator
University of Wisconsin, Madison
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ixazomib Oral Capsule in people with Kidney Diseases and End Stage Renal Disease, run by University of Wisconsin, Madison at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 May 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Efficacy of Ixazomib: Percentage of Participants With > 20 Percent Decline in Calculated Panel Reactive Antibody (cPRA) (time frame: up to 12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03213158, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jun 2022.