PRM-151 is being developed for potential therapeutic use to prevent, treat and reduce fibrosis. This study will provide an assessment of the safety, tolerability, pharmacokinetics and pharmacodynamics of PRM-151 after administration of ascending…
ID
Source
Brief title
Condition
- Other condition
- Lower respiratory tract disorders (excl obstruction and infection)
Synonym
Health condition
fibrose (idiopathische longfibrose)
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Safety will be evaluated from reported adverse events, scheduled physical
examinations, PFTs, vital signs, 12-lead ECGs, and clinical laboratory test
results.
Secondary outcome
Pharmacokinetics
Venous blood samples will be obtained to determine the pharmacokinetics (PK) of
endogenous levels of PTX-2 and PRM-151. Blood samples for PK (4 mL) will be
obtained on day 1, 2, 3, 5, 8, 15, 16, 17, 18, 19, 22, 29 and 57 at different
timepoints.
Pharmacodynamics
Pharmacodynamic (PD) blood samples (4mL) will be collected for the purpose of
exploratory analysis related to the effects, mechanism, dynamics and/or adverse
events of PRM-151. Fibrocytes, monocyte subsets, MMP-1, MMP-7, MMP-9, MCP1,
IP10, MDC, IL-6, IL-7, IL-8, IL-10, IL-1RA, TNFRSF1a, CCL18, and CCL-2 are
examples of biomarkers that may be examined based on the information gained
during the study and the biomarker strategy. Additional assays may be
performed that contribute to the objectives of the trial. Pharmacodynamic
samples will be collected on study days 1, 3, 5, 8, and 15 before test article
administration (predose, time 0) and on days 2, 16, 22, 29, 36, 43, and at
final study evaluation on day 57 (or upon early termination from the study) at
different timepoints.
Fibrocyte analysis
Blood samples (10 mL) will be collected for exploratory fibrocyte analysis on
study days 1, 3, 8, and 15 before test article administration (predose, time
0), and on days 22, 29, 36, 43, and at final study evaluation on day 57 (or
upon early termination from the study). Samples will also be collected during
the screening period; one sample to be collected between day -35 and day -28,
and a second sample between day -21 and day -14.
Immune response analysis
Immune response samples (4 mL) for antibody to PTX-2 will be collected on days
1 (predose), 29, and 57 (or upon early termination from the study).
Background summary
During a previous study, the safety of a new drug, known as PRM-151, has been
investigated in healthy volunteers and a small group of patients with
idiopathic fibrosis (IPF). This study is designed to investigate the effect of
PRM-151 in more detail in a larger group of IPF patients.
PRM-151 is a recombinant human Serum Amyloid P (rhSAP). SAP is a naturally
occurring protein that circulates in the bloodstream and plays a crucial role
in regulating wound healing. SAP's role is to regulate the activity of innate
immune cells including monocyte-derived cells (fibrocytes, macrophages,
dendritic cells) and myofibroblasts. The innate responses to injury can result
in excess collagen production and scarring. This excess collagen production is
an unwanted effect at surgical sites or in response to injury in a solid organ.
Studies show that maintaining an elevated level of SAP in the blood or locally
at the site of injury can prevent production of excess scarring and the
progression of fibrosis.
Study objective
PRM-151 is being developed for potential therapeutic use to prevent, treat and
reduce fibrosis. This study will provide an assessment of the safety,
tolerability, pharmacokinetics and pharmacodynamics of PRM-151 after
administration of ascending multiple intravenous (IV) doses to IPF patients.
Primary: To assess the safety and tolerability of ascending multiple IV doses
of PRM-151 in patients with IPF.
Secondary: To provide the PK and PD profile of ascending multiple IV doses of
PRM-151 in patients with IPF.
Study design
This is a randomized, double-masked, sponsor-unmasked, inpatient/outpatient,
sequential-group study of ascending multiple doses of PRM-151 administered
intravenously to patients with IPF.
Intervention
Multiple doses of PRM-151 (1mg/kg, 5mg/kg or 10mg/kg) will be evaluated in IPF
patients. The doses will be administered as an intravenous infusion over a time
period of 30 minutes. Each subject will participate in one cohort and will
receive either multiple doses of PRM-151 or placebo (0.9% saline), administered
in a randomized fashion.
Study burden and risks
Unexpected adverse events / Hypersensitivity reactions
Allergic reactions
Clinical significant findings during screening
Hematoma following venapunctures
Promedior Inc, 371 Phoenixville Pike
Malvern, PA 19355
US
Promedior Inc, 371 Phoenixville Pike
Malvern, PA 19355
US
Listed location countries
Age
Inclusion criteria
IPF patients
Age: 40 - 80 yrs (limits included)
BMI: 16-33 kg/m2
Body weight: >= 50 kg and <= 75 kg (The upper weight limit of <= 75 kg may be
increased or decreased depending upon the availability of test article.)
FVC >= 45%, corrected for age
DLCO: 35 to 80%
Exclusion criteria
History of amyloidosis, tuberculosis, cystic fibrosis, sarcoidosis or any other pulmonary disease other than IPF.
History of connective tissue disorder, severe pulmonary hypertension or COPD with an extent of emphysema
greater than the fibrosis.
Acute disease state.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2010-024508-89-NL |
| ClinicalTrials.gov | NCT01254409 |
| CCMO | NL35135.078.10 |