Read
the following information and if you have HAE yourself, THINK ABOUT
BECOMING A TRIAL VOLUNTEER. IT COULD HELP YOU WHILE HELPING OTHERS!
Several very exciting
medications for treating acute attacks of HAE are now undergoing
the detailed clinical trials required before they can be licensed
for prescription. All of these agents passed the initial laboratory
testing stages and were safety-tested in healthy volunteers who
did not have HAE. They were then used to treat acute attacks in
people with HAE, under heavily monitored trial conditions. Results
so far have been encouraging.
The new medications now
have to be tested against a ‘placebo’ or dummy infusion.
In most cases this means that neither patient nor doctor will know
whether the test medication or an inactive substance (usually salt
water) is being given. Of course, C1 inhibitor can be given at any
time if it is medically urgent or if the pain gets too severe.
Four products - C1 esterase
inhibitor, recombinant human C1 inhibitor, Icatibant and DX-88 are
due for clinical trials in the UK over the next few months, and
we strongly encourage HAE patients with appropriate symptoms to
volunteer.
C1 esterase Inhibitor
in subjects with congenital C1-INH deficiency and acute abdominal
or facial attacks
C1 esterase inhibitor is a plasma-derived intravenous therapy which
is being studied in the treatment and prevention of acute HAE. It
is thought that by replacing the missing physiological C1 protein,
this treatment could address the underlying mechanism of the disease
by controlling the involved mediator systems.
The purpose of this trial is to show that C1 esterase inhibitor
shortens the time to onset of relief of symptoms of abdominal or
facial HAE attacks compared to placebo.
Subjects may participate in this trial if they:
Have a diagnosis of hereditary C1-INH deficiency
Have a documented history of facial or abdominal
attacks
Are 6 years of age or older
Subjects may not participate in this trial if they:
Have been treated with any C1-INH product within
the previous 7 days
Have been treated with any investigational drug
within the last 30 days
Are being treated with an Angiotensin Converting
Enzyme (ACE) inhibitor
Other inclusion and exclusion
criteria exist; a participating hospital will provide additional
details.
This trial
has already started in the USA and is hoped to begin in the UK when
adequate volunteers have been recruited.
C1 esterase inhibitor
will be tested in two different dosages against a placebo. Neither
the subject nor the doctor will know whether the C1 esterase inhibitor
or the placebo is being given. The trial medication will be administered
intravenously via a slow injection/infusion. All subjects will need
to stay at the hospital for at least 4 hours. After 4 hours subjects
may be discharged if their symptoms have started to improve. Subjects
will have to make two follow-up visits to the hospital. The first
visit one week later and the second twelve weeks later.
Current Trial Centre Locations
This trial will be conducted at approximately 45 hospitals throughout
the United States, Canada and Europe. UK trials will be conducted
in London and possibly at other sites
Study with
subcutaneously administered Icatibant
Icatibant is a new medication currently being tested (in Phase III
trials) to assess its suitability as a treatment. When someone with
HAE has an acute attack of swelling this is because there is too
much of a hormone called bradykinin in the area of the swelling.
Icatibant can block the effects of bradykinin very powerfully, and
very specifically. Unlike C1 inhibitor, Icatibant can be given subcutaneously
(i.e. by injection under the skin), and is not purified from human
blood but is synthesised in a laboratory.
To date, Icatibant has been tested in over 850 people, with a variety
of different inflammatory conditions and has been shown to be safe
and well-tolerated.
In a previous similar trial, Icatibant was tested in 15 people with
HAE who were having an attack. Some of these were treated more than
once: in total 20 HAE attacks have been treated. At first the treatment
was given intravenously, but for patients receiving it more recently
it has been given subcutaneously. All the patients reported good
relief. The time to relief was on average 30 to 90 minutes- similar
to what we would expect for C1 inhibitor.
Jerini’s current
trials for Icatibant are being conducted in the U.S., Canada, Europe
and other countries. Laryngeal episodes have been already successfully
treated in the current trial. Except for laryngeal attacks, the
current trials compare the effects of Icatibant injection with those
of tranexamic acid tablets, and neither physician nor patient will
know which they have received. Jerini expects completion of these
ongoing trials in the fourth quarter of 2005 or early 2006. However,
patients who have had one treatment with Icatibant on this trial
will be eligible to receive Icatibant for further attacks, free
of charge to your hospital, and on these occasions will always receive
Icatibant. This is called the ‘Open-Label Extension phase’
and will last until Icatibant is licensed for prescription, probably
in 2006/2007.
Future Trial
Centre Locations
This trial is currently recruiting patients at St Bartholomew’s
Hospital, London and will soon be recruiting in Edinburgh, Newcastle,
and possibly more in the future
.
A randomized, placebo-controlled, double-blind Phase III study of
the efficacy and safety of recombinant human C1 inhibitor (rhC1INH)
for the treatment of acute attacks (Pharming C1 1304-01)
Severe HAE attacks are usually treated with C1 inhibitor, which
is purified from human plasma. Recently the Pharming company has
developed a method of producing recombinant C1 inhibitor. Unlike
the C1 inhibitor which is currently used, recombinant human C1inhibitor
(rh C1INH) is purified from the milk of rabbits, specially bred
to produce rhC1INH. Although currently used plasma-derived C1 inhibitors
are believed to be safe after the installment of specific measures,
the development of a recombinant product is even less likely to
be responsible for infectious disease. A recombinant product would
also overcome difficulties caused by shortages of human plasma.
People volunteering for this study can be treated for any type of
HAE attack; facial, abdominal or peripheral (arm/leg etc.) swellings.
Volunteers will be divided into 2 groups and neither the doctor
nor the patient will know which group they are in.
Group 1 will receive rhC1INH infusion
Group 2 placebo group (ie salt water; not likely to
be of any benefit)
People taking part will be monitored to see when pain and swelling
relief starts. Anyone developing very severe symptoms will be able
to receive standard of care (regular C1 inhibitor, if applicable)
at any time, if the physician thinks that it is necessary.
After treatment, progress will be monitored for 12 -24 hours after
which the volunteer will be able to go home. Expenses, including
long distance taxi if necessary, will be paid.
EDEMA3: Evaluation
of DX-88’s effects in mitigating angioedema
DX-88 is a novel drug
specifically designed for the treatment of HAE symptoms and is being
developed under a joint venture partnership between Dyax and Genzyme.
Experts believe that an HAE attack is initiated by the uncontrolled
generation of kallikrein that leads to the release of active peptides
that cause angioedema symptoms. DX-88 uniquely and specifically
acts on inhibiting kallikrein early on in the biological cascade.
The clinical research
programme aims to confirm that DX-88 results in rapid relief of
angioedema attacks. In the ongoing clinical study, 91% of patients
treated with DX-88 have shown improvement. DX-88 was shown to work
as early as a few minutes after treatment with a median time to
improvement of 30 minutes.
As a highly purified protein
manufactured by recombinant DNA technology, DX-88 does not share
the risks (e.g., viral contamination) associated with plasma or
animal-derived products. DX-88 has been administered over 380 times
in over 150 people. This includes over 230 treatments for acute
attacks of HAE in both children and adults, including abdominal,
peripheral and laryngeal attacks. Promising safety and efficacy
results have been demonstrated to date. In fact, of the new drugs
under development, DX-88 has been studied the most.
In the coming months Genzyme
and Dyax will be initiating a Phase 3 pivotal clinical trial with
DX-88 for the treatment of patients experiencing acute attacks associated
with HAE in Europe, US and Canada. This study is expected to satisfy
the requirements for approval by the European Medicines Agency.
EDEMA3 builds upon the
previous positive results of the EDEMA0, EDEMA1 and EDEMA2 studies
and will add to the large body of experience of DX-88 in the treatment
of HAE. Earlier studies administered DX-88 intravenously. However,
based on the keen interest of the patient community for more convenience
combined with recent successful studies supporting a new, easier
method of delivery, DX-88 is now being administered by subcutaneous
injection in ongoing studies. This method of administration will
be used in EDEMA3.
Full details of the protocol
design and participating investigational hospitals will be reported
in future issues of Insight and will be posted on the PIA website
shortly.
Volunteering
for a trial
We
still need clinical trial volunteers! Only FIVE people have contacted
us so far. Without HAE patients who volunteer the trials cannot
go ahead in the UK.
All of us would wish to
see the clinical trials completed successfully so that the medications
can be made available on prescription in the UK. However,
this will only happen if enough of us volunteer to participate in
the trials.
If you do take part, you
will have a detailed medical and examination and blood samples will
be taken. You will not normally attend for trial visits again until
you suffer from an acute attack of HAE. If you have an attack, you
will have the choice of your usual treatment, or contacting your
centre for trial treatment. When you attend, the treatment will
be given, you will be assessed by the staff, and blood tests taken
at frequent intervals to monitor your response and to ensure your
safety. Your travel expenses will be paid, including taxi fares
if you aren’t feeling well enough for public transport. In
some cases you may also receive a small payment to cover your other
expenses.
All HAE patients who would
like to volunteer for these vital trials should contact John
Satchell at the PIA (020 7976
7640) to be put in contact with a leading trial consultant.
Many thanks to those who
have already volunteered, you have made a major contribution to
the future of all those with HAE and AAE.
What can the P.I.A. do for me?
The Primary Immunodeficiency Association (P.I.A.) aims to improve
the quality of life of all people with primary immunodeficiencies.
For the H.A.E. sufferer we can provide a wide variety of services
and resources. These would include :
Publications such as the 'booklet'
Understanding Hereditary Angioedema and Acquired C1-Inhibitor Deficiency'.
P.I.A. information packs for the lay
person and the professional.
Regional Days at different locations
around the U.K. where members can meet up with others in similar
situations.
Assistance with benefits for those
who are too ill to work.
After Hours Helpline : 0845
6039158 is a telephone helpline available outside
office hours
Condition Specific Contact : speak
in confidence to another H.A.E. sufferer for advice and sharing
of experiences
Online forums
For more information on any of the above topics please contact the
P.I.A. through the home
page.
What is the Consensus Document?
The Consensus Document
represents the outcome of discussion and research on the best practice
for the diagnosis, treatment and management of C1-inhibitor deficiency.
It’s adoption will mean that there is a standard set out for
patients that will ensure uniformity of treatment (hopefully) throughout
the world.
Check out Andy Long’s
web site http://www.thirdbass.co.uk
to see publicity for HAE in ‘Wales on Sunday’. Anyone
who would be prepared to tell their HAE story to the media to help
raise the awareness of HAE should contact the PIA and ask to speak
to John.
We are looking for HAE
patients who might be able to help inthe next
Jeans for Genes campaign. Please contact Kate
at the PIA office to know more and to receive a Jeans for Genes
information pack.
