Investigation of Safety, Pharmacokinetics and Pharmacodynamics of Different Doses of BIWH 3 in Patients With Chronic Critical Limb Ischaemia

NCT02215824 | Terminated Phase 1

• 1 other identifier: 1181.1
• Study Type: interventional
• Target: 7
• Locations: 0 countries
• Sites: N/A

Brief Summary

The primary aim of this trial was to investigate the safety of a 6 hour intraarterial infusion of BIWH 3 (pyro-Glu-rhMCP-1) in patients with severe peripheral arterial occlusive disease (PAOD) and chronic Critical Limb Ischaemia (Fontaine class III or IV).

Conditions

Peripheral Arterial Disease

Outcome Measures

Primary Outcomes (10)

• Number of patients with adverse events

  up to 180 days after drug administration

• Number of patients with clinically relevant changes in vital signs (heart rate, blood pressure, body temperature)

  baseline, up to 180 days after drug administration

• Number of patients with clinically relevant changes in laboratory evaluations

  baseline, up to 180 days after drug administration

• Number of patients with clinically relevant changes in 12- lead electrocardiogram (ECG)

  baseline, up to 180 days after drug administration

• Number of patients with clinically relevant changes in markers of inflammation

  measured by C-reactive Protein (CRP) and erythrocyte sedimentation rate (ESR)

  baseline, up to 180 days after drug administration

• Number of patients with clinically relevant changes in ophthalmic examinations

  baseline, up to 180 days after drug administration

• Number of patients with changes from baseline in progression of atherosclerosis

  measured by carotid duplex imaging

  day 180

• Number of patients with changes in local disease defined by degree of stenosis

  assessed by magnetic resonance angiography

  up to 6 months post treatment

• Number of patients with changes from baseline in result of cancer screening

  day 180

• Number of patients developing an antibody response to BIWH 3

  baseline, up to 180 days

Secondary Outcomes (8)

• Changes in transcutaneous oxygen pressure (tcPO2)

  baseline, up to 180 days after drug administration

• Changes in lower extremity magnetic resonance angiography (MRA)

  baseline, up to 180 days after drug administration

• Changes in ankle brachial or toe brachial index

  baseline, up to 180 days after drug administration

• Occurence of amputations

  up to 180 days after drug administration

• Progression of ulcer healing

  up to 180 days after drug administration

Study Arms (2)

BIWH 3

EXPERIMENTAL

in escalating doses

Drug: BIWH 3

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

BIWH 3 DRUG

BIWH 3

Placebo DRUG

Placebo

Eligibility Criteria

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

You may qualify if:

• Patient must have severe PAOD with Chronic Critical Limb Ischaemia, Fontaine class III (ischaemic pain at rest) or IV (tissue ulceration or gangrene) due to atherosclerotic disease
• Patient must be \>= 18 years of age
• Patient must give written informed consent
• Patient must have a life expectancy of at least six months

You may not qualify if:

• Transient ischaemic attack (TIA), cerebral vascular accident (CVA), myocardial infarction (MI) or episode of unstable angina within the past two months
• Ophthalmologic conditions: moderate to severe nonproliferative retinopathy, proliferative retinopathy, age related maculopathy with choroidal neovascularisation, macular edema, intraocular surgery within the previous 6 months, retinal vein occlusion
• Presence of a clinically significant disease which in the opinion of the investigator may either put the patient at risk because of participation in the study or a disease which may influence the result of the study or the patient's ability to participate in the study
• ECG results outside of the reference range of clinical relevance including, but not limited to QTcB \> 480 msec, PR interval \> 240 msec, QRS interval \> 140 msec
• History of malignant disease, or a positive result on any of the required cancer screening tests, unless a definitive subsequent evaluation for cancer is determined to be negative
• Patients at increased risk of colorectal cancer, including any of the following (1) colorectal cancer pr polyps in a first-degree relative younger than 60 or in two first-degree relatives of any age, (2) family history of familial adenomatous polyposis or hereditary non-polyposis colon cancer, (3) history of adenomatous polyps, or (4) history of chronic inflammatory bowel disease (chronic ulcerative colitis or Crohn's disease)
• Abnormalities greater than two times the upper limit of normal in any of the following laboratory values at Visit 1: alanine-aminotransferase (ALT), aspartate-aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase or lactic dehydrogenase (LDH); abnormalities greater than 1.5 times the upper limit of normal of total bilirubin or white blood cell count
• Any concurrent infectious disease requiring treatment
• Severe renal insufficiency (estimated creatinine clearance \< 30 mL/min)
• Duffy antigen negative blood type with co-existing moderate to severe renal insufficiency (estimated creatinine clearance \< 80 mL/min), to avoid potential risk of significant increase of monocyte chemoattractant protein-1 (MCP-1) levels
• Known glomerulonephritis, even if creatinine clearance is apparently normal
• Thrombocytopenia, i.e. platelet count \<100,000 cells/μl at Visit 1
• History of drug or alcohol abuse within the past 2 two years or active drug or alcohol abuse, present alcohol intake more than three drinks per day
• Inability to comply with the protocol
• Treatment with an investigational drug within 30 days or 5 half-lives, whichever is greater before Visit 2

Sponsors & Collaborators

• Boehringer Ingelheim: lead

MeSH Terms

Conditions

Peripheral Arterial Disease

Condition Hierarchy (Ancestors)

Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 12, 2014
• First Posted: August 13, 2014
• Study Start: October 1, 2002
• Primary Completion: October 1, 2003
• Last Updated: August 22, 2014

Record last verified: 2014-08