Efficacy and Safety of IL-11 in DDAVP Unresponsive

NCT00994929 | Completed Phase 2 Results

• 1 other identifier: PRO08070154, Wyeth 3067K1-2214
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine the biologic efficacy and safety of rhIL-11 when given subcutaneously in adults with moderate or mild hemophilia A or Von Willebrand disease unresponsive to DDAVP. Biologic efficacy will be measured by the number and percent increase of VWD coagulation tests (FVIII:C, VWF: Ag, VWF: RCo, closure time, APTT, and VWF multimers) to the normal range, or at least to 1.5-3 time baseline, following dosing of rhIL-11 when given daily for 4 days, and boosted by DDAVP infusion on day 4, in those in whom DDAVP is not contraindicated. Safety will be measured by the frequency of adverse events, including fever, headache, fatigue, myalgias, arthralgias, fluid retention, or edema.

Conditions

Hemophilia A; Von Willebrand Disease

Keywords

biologic effects; von Willebrand disease; hemophilia; interleukin-11; DDAVp

Outcome Measures

Primary Outcomes (1)

• Biologic Effects by Coagulation Tests

  VWF activity was measured by ristocetin-induced platelet agglutination using a Chronolog aggregometer11-14 and VWF:Ag by "sandwich" ELISA, using anti-VWF antibodies (DakoA082, Carpintera CA). Results were expressed in percent, with normal human plasma pool designated 100%, and severe type 3 VWD plasma used as the negative control

  within 4 days of study drug.

Secondary Outcomes (2)

• The Frequency of Adverse Events

  within 11 days of study drug

• The Mechanism of Study Drug Effect by VWF mRNA.

  within 11 days of study drug.

Study Arms (1)

Neumega (Oprelveken, Interleukin 11)

EXPERIMENTAL

Neumega (Oprelveken, interleukin-11 (IL-11) 25 microgram/kilogram by subcutaneou injection once daily for four days, followed on day 4 DDAVP 0.3 microgram/kilogram intravenously 30 minutes after neumega

Biological: Neumega (Oprelvekin, Interleukin 11, IL-11)

Interventions

Neumega (Oprelvekin, Interleukin 11, IL-11) BIOLOGICAL

25 microgram/kg IL-11 by subcutaneous injection once daily for four days, followed by DDAVP 0.3 microgram/kg by intravenous infusion over 30 minutes on day 4, 30 minutes after IL-11.

Also known as: Interleukin-11, IL-11, Oprelvekin

Neumega (Oprelveken, Interleukin 11)

Eligibility Criteria

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

You may qualify if:

• Males or females \>= 18 years of age.
• A diagnosis of hemophilia A, moderate (FVIII:C 0.01-0.04 U/ml) or mild (FVIII:C \>= 0.05 U/ml); or a diagnosis of VWD, defined by a low VWF:RCo and past bleeding history.
• For those with VWD, an inability to use DDAVP due to i) unresponsiveness defined as VWF:RCo or FVIII:C level lower than 50 IU/dl or less than a 3-fold increase after 0.3 microgram/kg DDAVP; ii) allergic reactions or seizures; or iii) a contraindication to DDAVP.
• Willingness to have blood drawn.
• Willingness to sign informed consent.

You may not qualify if:

• Presence of other bleeding disorders, acquired Von Willebrand disease, primary thrombocytopenia.
• Use of immunomodulatory or experimental drugs, or diuretics.
• Pregnant or lactating women.
• Previous cardiac disease, congestive failure, arrhythmia (e.g. atrial fibrillation, atrial flutter), hypertension, MI, stroke, or thrombosis.
• Past allergic reaction to Neumega.
• Surgery within the past 8 weeks.
• Inability to comply with study protocol requirements.
• Concomitant use of antiplatelet drugs, anticoagulants, dextran, aspirin or NSAIDs.
• Treatment with DDAVP, cryoprecipitate, whole blood, plasma and plasma derivatives containing substantial quantities of FVIII and/or VWF within five days of study.
• Baseline safety and/or hematology lab values outside the normal limits and/or an EKG indicating an arrhythmia.

Sponsors & Collaborators

• University of Pittsburgh: lead

Study Sites (1)

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (2)

• Ragni MV, Jankowitz RC, Chapman HL, Merricks EP, Kloos MT, Dillow AM, Nichols TC. A phase II prospective open-label escalating dose trial of recombinant interleukin-11 in mild von Willebrand disease. Haemophilia. 2008 Sep;14(5):968-77. doi: 10.1111/j.1365-2516.2008.01827.x. Epub 2008 Aug 1.

  PMID: 18680527 BACKGROUND

• Ragni MV, Novelli EM, Murshed A, Merricks EP, Kloos MT, Nichols TC. Phase II prospective open-label trial of recombinant interleukin-11 in desmopressin-unresponsive von Willebrand disease and mild or moderate haemophilia A. Thromb Haemost. 2013 Feb;109(2):248-54. doi: 10.1160/TH12-06-0447. Epub 2012 Dec 13.

  PMID: 23238591 DERIVED

MeSH Terms

Conditions

Hemophilia A; von Willebrand Diseases

Interventions

oprelvekin; Interleukin-11

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Blood Platelet Disorders

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: Margaret V. Ragni, MD, MPH
• Organization: The University of Pittsburgh

ragni@pitt.edu

412-209-7288

Study Officials

• Margaret V. Ragni, MD, MPH

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Laurel Yasko

Study Record Dates

• First Submitted: October 12, 2009
• First Posted: October 14, 2009
• Study Start: January 1, 2010
• Primary Completion: April 1, 2012
• Study Completion: April 1, 2012
• Last Updated: March 2, 2016
• Results First Posted: March 2, 2016

Record last verified: 2016-02

Locations

US (1)