AzTrials
AzTrials

Transplant; Failure, KidneyPhase 1NCT01163799

A Pilot Study to Assess the Safety and Efficacy of Alefacept in de Novo Kidney Transplant Recipients

A Phase 1 study testing Alefacept (ASP0485) in people with Transplant; Failure, Kidney, run by Northwestern University at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

The purpose of this study is to assess Alefacept in combination with alemtuzumab induction and calcineurin inhibitor and corticosteroid withdrawal. Read more about this study

Who is it for?
Ages 18 years and olderHealthy volunteers can take part
Conditions the study is for
Transplant; Failure, Kidney
What is being tested?
Alefacept (ASP0485)
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
1 siteUnited States
Study dates
Jul 2010to Aug 2012
Phase
Phase 1
Are there results?
None posted in the registry

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 years and older
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Institutional Review Board (IRB) approved written Informed Consent and Health Insurance Portability and Accountability Act (HIPAA) Authorization for U.S. sites, or equivalent privacy language as per national regulations, obtained from the subject or legally authorized representative prior to study-related procedures (including withdrawal of prohibited medication, if applicable)
  • Recipient of a kidney from a non-HLA identical related living donor, a non- related living donor, or deceased donor
  • Recipient of a de novo kidney transplant
  • ≥ 18 years of age
  • Anticipated to receive first oral dose of tacrolimus within 48 hours of transplant procedure
  • Female subjects of child bearing potential must have a negative urine or serum pregnancy test, and must agree to maintain effective birth control during the study
Show all 10Show fewer
  • Healthy donor is eligible for the blood draw if:
  • Institutional Review Board (IRB) approved written Informed Consent and Health Insurance Portability and Accountability Act (HIPAA) Authorization for U.S. sites, or equivalent privacy language as per national regulations, is obtained from subject prior to any study-related procedures
  • Subject is a donor to a de novo kidney transplant subject who is enrolled in the study or a self declared healthy volunteer who is not a kidney donor for a subject enrolled in the study
  • ≥ 18 years of age

Who cannot join

  • Previously received or is receiving an organ transplant other than a kidney
  • Sensitivity to iodine
  • Will receive a transplant from a non-heart beating donor (donation after cardiac death - DCD)
  • Receives a transplant from an HLA identical related living donor
  • Will receive a solitary kidney from a deceased donor < 5 years of age
  • Will receive a kidney with an anticipated cold ischemia time (CIT) of > 30 hours
Show all 25Show fewer
  • Will receive an ABO incompatible donor kidney
  • Recipient or donor is known to be seropositive for human immunodeficiency virus (HIV)
  • Recipient has a positive T or B cell crossmatch by investigational site's standard method of determination. For recipients where a flow cytometry crossmatch is performed and is positive in either T or B cell testing, recipients are excluded only if donor specific, anti-HLA antibody is detected by flow cytometry based, specific anti-HLA antibody testing.
  • Current malignancy or a history of malignancy (within the past 5 years), except non-metastatic basal or squamous cell carcinoma of the skin that has been treated successfully
  • Significant liver disease
  • Serologically negative for cytomegalovirus (CMV) with serologically positive CMV donor
  • Serologically negative for Epstein Barr virus
  • Has received intravenous immunoglobulin (IVIG) therapy in the three months prior to first dose of study drug
  • Uncontrolled concomitant infection or any other unstable medical condition that could interfere with the study objectives
  • Concurrently participating in another drug study or has received an investigational drug within 28 days prior to transplant
  • Known hypersensitivity to alefacept, alemtuzumab, tacrolimus, mycophenolic acid, corticosteroids, or any of their components
  • Any form of substance abuse, psychiatric disorder, or a condition that in the opinion of the Investigator could invalidate communication with the Investigator
  • Subject is pregnant or lactating
  • Subject is unlikely to comply with the visits scheduled in the protocol
  • Subject will receive a kidney transplant from an expanded criteria donor (ECD)
  • Will receive a kidney transplant from a CDC high risk donor
  • Healthy donor subject will be excluded from participation if any of the following apply:
  • Unable to comprehend the investigational nature of the protocol participation
  • Complete blood count results determined to be outside the normal ranges

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Northwestern Memorial Hospital

    Chicago, Illinois, 60611

Other trials in United States

About this study

The purpose of this study is to assess Alefacept in combination with alemtuzumab induction and calcineurin inhibitor and corticosteroid withdrawal.

Read the detailed description

This is a single center, investigator initiated, pilot study to assess the safety and efficacy of Alefacept in combination with Alemtuzumab induction and Myfortic with rapid steroid and calcineurin inhibitor withdrawal in de novo Kidney transplant recipients. Induction therapy involves single dose Alemtuzumab and steroids peri-operatively. Tacrolimus will be administered for the first 30 days post-transplantation. Alefacept will be administered IV for the first two doses followed by subcutaneous injections weekly until 12 weeks post-transplant followed by monthly injections for the rest of the duration of the study. The primary outcomes are safety and efficacy outcomes, including biopsy proven acute rejection episodes, infectious complications or other serious adverse events. Secondary outcomes include T-helper differentiation, cytokine production and T regulatory cell generation assessed by immune monitoring assays.

Being tested
Alefacept (ASP0485)
Keywords
Kidney, Transplant, Northwestern, Calcineurin Inhibitor, Corticosteroids, Steroid avoidance

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Alefacept (ASP0485)Drug

    Also called ASP0485

    Withdrawal of calcineurin inhibitor at 30 days post-transplant. Administer Alefacept 7.5 mg post-op day 0, post-op day 2 given IV; Alefacept 15 mg SQ X 12 weeks, then monthly until Month 12.

Study groups in NCT01163799
Study groupRoleWhat they receive
Alefacept (ASP0485)ExperimentalSafety and efficacy of alefacept in combination with alemtuzumab induction and calcineurin inhibitor (CNI) and corticosteroid withdrawal.
Receives: Drug: Alefacept (ASP0485)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of first biopsy- proven acute rejection (Banff Grade≥ 1) (BCAR rate) and infections

    To assess the safety and efficacy of alefacept in combination with a single dose of alemtuzamab induction and Enteric coated Mycophenolic sodium with calcineurin inhibitor withdrawal and rapid elimination of corticosteroids by examining the incidence of first biopsy-proven acute rejection (Banff Grade≥ 1) (BCAR rate) and the incidence and clinical presentation of infections.

    Measured: At 12 months post-transplant

Secondary outcomes (2)
  1. Affect on Immune cells

    To assess how alefacept affects T-cell differentiation, memory, and immunoregulatory T-cell homeostasis, B-cells and cytokine/chemokine profile by using various immune monitoring assays.

    Measured: Up to 12 months post-transplant

  2. Assess secondary outcome measures of efficacy and safety

    At 12 months: Patient/graft survival rates, BCAR rate, Maximum grade of acute rejection with BCAR, Incidence of clinically-treated acute rejections, Incidence of anti-lymphocyte antibody therapy for treatment of rejection, Incidence of multiple rejection episodes, Incidence of treatment failure (defined as death, graft loss, biopsy-confirmed acute rejection, lost to follow-up or early discontinuation of treatment regimen), Incidence of leucopenia, Incidence of bacterial, fungal, viral, or parasitic infection. At 6 \& 12 months: Serum creatinine, GFR by iohexol clearance. Time to first BCAR

    Measured: Upto 12 months post-transplant

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Jul 2010 (estimated)
  2. Study startJul 2010
  3. Primary completionSep 2011
  4. Study completionAug 2012

Why it stopped: Noted increased risks, greater than expected for standard of care therapy.

Resources

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01163799
Sponsor's protocol ID
STU 00029396
Other IDs
640 5442000 60026221 01
Status last verified
May 2013
First submitted
14 Jul 2010
Last updated
3 May 2013
Results posted
No
Data monitoring committee
Yes

Publications

  • Ansari MJ, Sayegh MH. The arduous road to achieving an immunosuppression-free state in kidney transplant recipients. Nat Clin Pract Nephrol. 2007 Sep;3(9):464-5. doi: 10.1038/ncpneph0568. Epub 2007 Jul 24. No abstract available.

    PubMed 17646858
  • Antonysamy MA, Fanslow WC, Fu F, Li W, Qian S, Troutt AB, Thomson AW. Evidence for a role of IL-17 in alloimmunity: a novel IL-17 antagonist promotes heart graft survival. Transplant Proc. 1999 Feb-Mar;31(1-2):93. doi: 10.1016/s0041-1345(98)01453-5. No abstract available.

    PubMed 10083023
  • Beninga J, Kropff B, Mach M. Comparative analysis of fourteen individual human cytomegalovirus proteins for helper T cell response. J Gen Virol. 1995 Jan;76 ( Pt 1):153-60. doi: 10.1099/0022-1317-76-1-153.

    PubMed 7844526
  • Besse T, Malaise J, Mourad M, Pirson Y, Hope J, Awwad M, White-Scharf M, Squifflet JP. Prevention of rejection with BTI-322 after renal transplantation (results at 9 months). Transplant Proc. 1997 Aug;29(5):2425-6. doi: 10.1016/s0041-1345(97)00432-6. No abstract available.

    PubMed 9270793
  • Bishop DK, Chan Wood S, Eichwald EJ, Orosz CG. Immunobiology of allograft rejection in the absence of IFN-gamma: CD8+ effector cells develop independently of CD4+ cells and CD40-CD40 ligand interactions. J Immunol. 2001 Mar 1;166(5):3248-55. doi: 10.4049/jimmunol.166.5.3248.

    PubMed 11207279
  • Bobadilla JL, Love RB, Jankowska-Gan E, Xu Q, Haynes LD, Braun RK, Hayney MS, Munoz del Rio A, Meyer K, Greenspan DS, Torrealba J, Heidler KM, Cummings OW, Iwata T, Brand D, Presson R, Burlingham WJ, Wilkes DS. Th-17, monokines, collagen type V, and primary graft dysfunction in lung transplantation. Am J Respir Crit Care Med. 2008 Mar 15;177(6):660-8. doi: 10.1164/rccm.200612-1901OC. Epub 2008 Jan 3.

    PubMed 18174545
  • Burlingham WJ, Love RB, Jankowska-Gan E, Haynes LD, Xu Q, Bobadilla JL, Meyer KC, Hayney MS, Braun RK, Greenspan DS, Gopalakrishnan B, Cai J, Brand DD, Yoshida S, Cummings OW, Wilkes DS. IL-17-dependent cellular immunity to collagen type V predisposes to obliterative bronchiolitis in human lung transplants. J Clin Invest. 2007 Nov;117(11):3498-506. doi: 10.1172/JCI28031.

    PubMed 17965778
  • Chamian F, Lin SL, Lee E, Kikuchi T, Gilleaudeau P, Sullivan-Whalen M, Cardinale I, Khatcherian A, Novitskaya I, Wittkowski KM, Krueger JG, Lowes MA. Alefacept (anti-CD2) causes a selective reduction in circulating effector memory T cells (Tem) and relative preservation of central memory T cells (Tcm) in psoriasis. J Transl Med. 2007 Jun 7;5:27. doi: 10.1186/1479-5876-5-27.

    PubMed 17555598
  • Chisholm PL, Williams CA, Jones WE, Majeau GR, Oleson FB, Burrus-Fischer B, Meier W, Hochman PS. The effects of an immunomodulatory LFA3-IgG1 fusion protein on nonhuman primates. Ther Immunol. 1994 Aug;1(4):205-16.

    PubMed 7584496
  • Cooper JC, Morgan G, Harding S, Subramanyam M, Majeau GR, Moulder K, Alexander DR. Alefacept selectively promotes NK cell-mediated deletion of CD45R0+ human T cells. Eur J Immunol. 2003 Mar;33(3):666-75. doi: 10.1002/eji.200323586.

    PubMed 12616487
  • Crawford K, Gabuzda D, Pantazopoulos V, Xu J, Clement C, Reinherz E, Alper CA. Circulating CD2+ monocytes are dendritic cells. J Immunol. 1999 Dec 1;163(11):5920-8.

    PubMed 10570278
  • Crispim JC, Grespan R, Martelli-Palomino G, Rassi DM, Costa RS, Saber LT, Cunha FQ, Donadi EA. Interleukin-17 and kidney allograft outcome. Transplant Proc. 2009 Jun;41(5):1562-4. doi: 10.1016/j.transproceed.2009.01.092.

    PubMed 19545679
  • da Silva AJ, Brickelmaier M, Majeau GR, Li Z, Su L, Hsu YM, Hochman PS. Alefacept, an immunomodulatory recombinant LFA-3/IgG1 fusion protein, induces CD16 signaling and CD2/CD16-dependent apoptosis of CD2(+) cells. J Immunol. 2002 May 1;168(9):4462-71. doi: 10.4049/jimmunol.168.9.4462.

    PubMed 11970990
  • Dasgeb B, Holzman G, Phillips TJ. An extended 16-week course of alefacept in conjunction with reduced T-cell monitoring for the treatment of chronic plaque psoriasis. Poster P2720, American Academy of Dermatology 2005 Annual Meeting, New Orleans, Louisiana, February 2005.

  • Dhanireddy KK, Bruno DA, Zhang X, Leopardi FV, Johnson LB, et al. Alefacept (LFA-3-Ig), portal venous donor specific transfusion, and sirolimus prolong renal allograft survival in non-human primates. Abstract 1627, American College of Surgeons 2006 Clinical Congress, Poster Session: Primate Models 2006 Jul 24.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Alefacept (ASP0485) in people with Transplant; Failure, Kidney, run by Northwestern University 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 10 inclusion and 25 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: stopped early, as of the sponsor's last update on 3 May 2013. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Noted increased risks, greater than expected for standard of care therapy.). Results are not available in the source record.

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?

Incidence of first biopsy- proven acute rejection (Banff Grade≥ 1) (BCAR rate) and infections (time frame: At 12 months post-transplant). 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 NCT01163799, which also lists 60 linked publications.

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 3 May 2013.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in