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

NCT00617604 | Completed Phase 2 Results DMC

• 2 other identifiers: 0485-CL-E2012007-002092-14
• Study Type: interventional
• Target: 218
• Locations: 12 countries
• Sites: 33

Brief Summary

The purpose of this study is to determine whether alefacept is effective and well tolerated when used with a combination of tacrolimus, mycophenolate mofetil and steroids versus a combination therapy of placebo, tacrolimus and steroids in the prevention of kidney transplant rejection.

Conditions

De Novo Kidney Transplantation

Keywords

kidney transplant; alefacept

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Biopsy-confirmed Acute T-cell Mediated Rejection at Month 6 Assessed by Local Review

  Biopsies were graded by the clinical site pathologist.according to the Banff 97/05 updated histological classification: * Grade IA: significant interstitial infiltration (\>25% parenchyma affected) and foci of moderate tubulitis; * Grade IB: significant interstitial infiltration (\>25% parenchyma affected) and foci of severe tubulitis; * Grade IIA: mild to moderate intimal arteritis; * Grade IIB: severe intimal arteritis comprising \>25% of the luminal area; * Grade III: "transmural" arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocyte inflammation. A biopsy confirmed acute rejection was an event of suspected acute rejection confirmed by a graft biopsy result of Banff grade ≥ 1. The Kaplan-Meier estimate of biopsy-confirmed acute T-cell mediated rejection within the first 6 months following transplantation is reported. Participants lost to follow-up or with missing outcomes were censored at their last follow up visit.

  6 months

Secondary Outcomes (19)

• Percentage of Participants With Biopsy Confirmed Antibody-Mediated Acute Rejection at Month 6

  6 months

• Percentage of Participants With Biopsy Confirmed Acute Rejection (T-Cell Mediated or Antibody Mediated) at Month 6

  6 months

• Percentage of Participants With Biopsy Confirmed Acute Mixed T-Cell Mediated and Antibody-Mediated Rejection at Month 6

  6 months

• Percentage of Participants With Acute Rejection Diagnosed by Signs and Symptoms at Month 6

  6 months

• Percentage of Participants With Clinically Treated Acute Rejection at Month 6

  6 months

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Participants received placebo administered intra-operatively as an intravenous (IV) bolus on Day 0, another IV bolus on Day 3 and weekly subcutaneous injections thereafter for 12 weeks. Participants also received tacrolimus, mycophenolate mofetil (MMF) and steroid treatment.

Drug: placebo; Drug: Tacrolimus; Drug: Mycophenolate Mofetil; Drug: Steroids

Alefacept

EXPERIMENTAL

Participants received 7.5 mg alefacept administered intra-operatively as an IV bolus on Day 0, another 7.5 mg IV bolus on Day 3, and weekly subcutaneous injections of 15 mg alefacept thereafter for 12 weeks. Participants also received tacrolimus, MMF and steroid treatment.

Drug: Alefacept; Drug: Tacrolimus; Drug: Mycophenolate Mofetil; Drug: Steroids

Interventions

Alefacept DRUG

IV and subcutaneous injection

Also known as: Amevive

Alefacept

placebo DRUG

IV and subcutaneous injection

Placebo

Tacrolimus DRUG

The initial daily dose was 0.2 mg/kg orally given in 2 doses commencing 24 hours after completion of surgery.

Alefacept; Placebo

Mycophenolate Mofetil DRUG

Mycophenolic mofetil was administered as 750 mg twice per day orally

Alefacept; Placebo

Steroids DRUG

Methylprednisolone or equivalent: Day 0: 500 - 1000 mg IV bolus Day 1: 125 - 250 mg IV bolus Prednisone or equivalent: Days 2 - 14: 20 - 30 mg orally Days 15 - 28: 10 - 20 mg orally Days 29 - 60: 10 - 15 mg orally Days 61 onwards: 5 - 10 mg orally

Alefacept; Placebo

Eligibility Criteria

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

You may qualify if:

• Subject with end stage kidney disease who is a suitable candidate for primary kidney transplantation or retransplantation
• Male or female subject at least 18 years of age and younger than 65 years
• Subject receiving a kidney transplant from a non-human leucocyte antigen (HLA) identical living donor or deceased HLA identical/non-HLA identical donor between 5 and 59 years of age with compatible ABO blood type (Blood group system A, B, AB and 0)

You may not qualify if:

• Subject has a panel reactivity antibody grade \> 20% in the previous 6 months and/or had had a previous graft survival shorter than 1 year due to immunological reasons
• Subject received a kidney transplant from a non-heart beating donor
• Subject has received a kidney transplant from a 50 - 59 year old donor with two of the following three factors: history of hypertension, cerebrovascular accident as cause of death, final pre-procurement serum creatinine \> 1.5 mg/dL (united network for organ sharing \[UNOS\] expanded criteria donor)
• Cold ischemia time of the donor kidney is ≥ 30 hours

Sponsors & Collaborators

• Astellas Pharma Inc: lead

Study Sites (33)

Unknown Facility

Vienna, 1090, Austria

Location

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Brussels, 1070, Belgium

Location

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Brussels, 1200, Belgium

Location

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Ghent, 9000, Belgium

Location

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Leuven, 3000, Belgium

Location

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Liège, 4000, Belgium

Location

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Prague, 140 21, Czechia

Location

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Créteil, 94010, France

Location

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Le Kremlin-Bicêtre, 94275, France

Location

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Montpellier, 34295, France

Location

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Nantes, 44093, France

Location

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Nice, 6002, France

Location

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Paris, 75475, France

Location

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Toulouse, 31054, France

Location

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Bochum, 44892, Germany

Location

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Regensburg, 93053, Germany

Location

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Budapest, 1082, Hungary

Location

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Bologna, 40138, Italy

Location

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Padua, 35128, Italy

Location

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Rome, 00168, Italy

Location

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Siena, 53100, Italy

Location

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Maastricht, 6229, Netherlands

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Bydgoszcz, 85-094, Poland

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Poznan, 60-479, Poland

Location

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Szczecin, 70-111, Poland

Location

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Barcelona, 8036, Spain

Location

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Llobregat, 8907, Spain

Location

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Madrid, 28041, Spain

Location

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Málaga, 29010, Spain

Location

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Santander, 39008, Spain

Location

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Gothenburg, 41345, Sweden

Location

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Uppsala, 75185, Sweden

Location

Unknown Facility

Manchester, M13 9WL, United Kingdom

Location

MeSH Terms

Interventions

Alefacept; Tacrolimus; Mycophenolic Acid; Steroids

Intervention Hierarchy (Ancestors)

CD58 Antigens; Membrane Glycoproteins; Glycoproteins; Glycoconjugates; Carbohydrates; Immunoglobulin G; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Membrane Proteins; Recombinant Fusion Proteins; Recombinant Proteins; Macrolides; Lactones; Organic Chemicals; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Senior Director Medical Science
• Organization: Astellas Pharma Europe B.V

Astellas.resultsdisclosure@astellas.com

Study Officials

• Central Contact

  Astellas Pharma Europe B.V.

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 6, 2008
• First Posted: February 18, 2008
• Study Start: December 1, 2007
• Primary Completion: September 1, 2009
• Study Completion: September 1, 2009
• Last Updated: February 4, 2016
• Results First Posted: February 4, 2016

Record last verified: 2016-01

Locations

HU (1); AU (1); FR (7); ES (5); NL (1); IT (4); BE (5); CZ (1); PL (3); SE (2); GB (1); DE (2)