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Clinical Trials & Research Studies

Several Clinical trials are underway to study treatments for NPB and NPC and natural history of NPC:

Past Clinical Trials:

Clinical Research and Services Funded by the National Niemann-Pick Disease Foundation

Glossary of Terms:

FDA United States Food and Drug Administration
HDAC Histone Deacetylase Inhibitors
ICV Intracerebroventricular
IND Investigational New Drug
i-IND Individual Investiational New Drug
IRB Institutional Review Board
NICHD National Institute of Child Health and Human Development
NIH National Institutes of Health
NPC Niemann-Pick Disease Type C Disease
TRND Therapeutics for Rare and Neglected Diseases

National Institutes of Health
Clinical Trial Updates for Niemann-Pick Type C Disease
June 27th, 2014
*Cyclodextrin and HDAC Inhibitor*

Update from Dr. Forbes D. Porter, MD, PhD
Senior Investigator, PDEGEN, NICHD
Program Head, PDEGEN, NICHD
Clinical Director, NICHD

The NNPDF central offices received the following update from Dr. Forbes D. Porter to share with the community in regards to recent developments in both the Cyclodextrin and new Histone Deacetylase Inhibitors (HDACi) clinical trials.

The TRND team continues to work to determine if cyclodextrin is a safe and effective therapy for children and young adults with Niemann-Pick Disease, type C1. This trial was initially started in January 2013 using Ommaya reservoirs; however, after three patients we had to stop the trial due to complications.  The trial was revised to administer the cyclodextrin by lumbar intrathecal infusion (spinal tap).  We were able to resume the trial in September of 2013 and to date we have enrolled twelve patients in whom we have studied cyclodextrin doses between 50 and 400 mg.  Some of the initial biomarker results look promising and we expect to obtain results from additional biomarker testing over the next few months.   From a safety perspective we are still concerned about ototoxicity (hearing loss) and we are working to try to better understand this issue.  Concurrent with this first trial we are working on a number of options that would support a phase II/III trial that would try to show that cyclodextrin has clinical benefit.    This second trial will need to be multisite and multinational.

For more information about the Cyclodextrin Clinical Trial, visit the Cyclodextrin page.

In addition to cyclodextrin, we are also exploring the potential use of histone deacetylase inhibitors (HDACi) to treat NPC1. The Maxfield and Sturley research groups showed that HDACi can reduce cholesterol storage in cells that have been cultured from NPC1 patients.     Over the past year we have been working to establish a proof of concept clinical trial of HDAC inhibition in NPC1.  A proposal to evaluate HDACi in NPC1 was awarded one of the first U01 grants (Drs. Maxfield, Ory and Porter) designed to promote extramural utilization of the NIH Clinical Center ( http://www.nih.gov/news/health/mar2014/nichd-13.htm ).  This collaboration has now been expanded this intramural/extramural collaboration to include investigators from Notre Dame (Drs. Helquist and Wiest), Broad Institute (Dr. Holson) and Mayo Clinic (Dr. Patterson).   This effort is being supported by Notre Dame College of Science and the Ara Parseghian Medical Research Foundation. The initial drug to be tested will be vorinostat.  Vorinostat is approved by the FDA for the treatment of cutaneous T-cell lymphoma.  Since this is a proof of concept trial and the safety of this drug in NPC subjects is not likely to differ significantly from patients with cutaneous T-cell lymphoma who have failed alternative chemotherapy, we were able to obtain a waiver of the requirement for an Investigational New Drug application for the testing of vorinostat in adult subjects with NPC1.  The NICHD Institutional Review Board (IRB) has approved a protocol to test the safety and efficacy of vorinostat in a cohort of 12 adult NPC1 subjects and we are currently working on IRB approval for a second site at the Mayo Clinic.  This will be a phase I proof of concept trial that will focus on safety of HDACi in NPC1 subjects and determine if HDAC inhibition has a desirable biochemical effect in white blood cells.  Although we still have a number of issues to resolve, it is our goal to initiate this protocol this fall.

For more information about the Histone Deacetylase Inhibitors Trial, visit the HDACi page .

[Jun 27th, 2014 ~ blg]

Update from Genzyme on
Acid Sphingomyelinase Deficiency (ASMD) Development Efforts
June 13th, 2014

Dear NNPDF Families and friends,

The NNPDF Central Offices received the following update from Genzyme (a Sanofi Company) in reference to the current Enzyme Replacement Therapy clinical 1b phase trial provided on June 13th, 2014:

" Genzyme, a Sanofi company, is pleased to update the Niemann-Pick disease patient community on the progress of efforts to develop a potential therapy for acid sphingomyelinase deficiency (ASMD, also known as Niemann-Pick disease Types A and B).

Genzyme completed a Phase 1b trial in Niemann-Pick disease Type B adult patients in January 2014. The Phase 1b trial evaluated the safety and tolerability of an investigational enzyme replacement therapy recombinant human acid sphingomyelinase (rhASM) when administered once every 2 weeks. Five adult patients with Niemann-Pick B disease were enrolled and completed the trial  at two study centers, Mount Sinai in New York, NY, US, and St. Mary’s Hospital in Manchester, UK. At this point in time, we are reviewing and preparing the final analyses of the Phase 1b trial.  The results of the Phase 1b trial will allow us to develop and plan future studies and to have a discussion with regulators such as FDA and EMA concerning our next step in the process.

While Genzyme continues to evaluate the results of the Phase 1b trial and prepare for meetings with the regulatory authorities, Genzyme continues to make progress preparing for a Phase 2 trial to further evaluate the safety and efficacy of different doses of rhASM when administered once every two weeks for one year. The Phase 2 study will be a multi-center, international, 1-year placebo-controlled trial to investigate the safety and efficacy of rhASM in adults with Niemann-Pick disease Type B. Participant enrollment for the Phase 2 study will begin after the results of the Phase 1b clinical trial have been fully evaluated, we have had the opportunity to discuss the results with regulatory authorities, and the trial sites are activated.

Genzyme remains committed to the Niemann-Pick community and will keep you updated as our development program continues. "

The NNPDF will continue to keep you updated as we receive further updates pertaining to this important research and clinical work on behalf of our Niemann-Pick Disease type A and B (ASMD) community.

[June 16, 2014 ~ blg]

~Cyclodextrin Update~ 02/25/2014
NIH Update on NPC Cyclodextrin Trial

Dear NNPDF Families and Friends,

We received the following update from Dr. Denny Porter with reference to the NIH/TRND Cyclodextrin Clinical:

Dr. Porter advised:
“We have hit a potential safety issue with the HPBCD trial.  The initial two kids who received the 300 mg dose demonstrated a grade 1 high frequency hearing loss on safety testing.  Grade 1 is the lowest level of severity.   Five other children have been exposed to the 300 mg dose.    We do not yet have safety testing on this group.  We will obtain this information over the next 3-4 weeks. We do not yet know if this is an idiosyncratic (the initial two kids are siblings) reaction or if this is going to be a general issue.   We have engaged the IRB and safety committee.  We will be engaging the FDA.   Our goals are to determine if we have a general safety issue and to figure out the best path forward.   Beyond the statement that a problem with hearing has been encountered and we are trying to figure out the safest and best way forward, there is not much that we can say.  There are multiple hypothetical paths forward at this time and the final plan is subject to information that we don’t have yet and input from other groups.  The uncertainty will remain for much of the next month.    We are not halting the trial.”

Denny
Forbes D. Porter, MD, PhD
Senior Investigator, PDEGEN, NICHD
Program Head, PDEGEN, NICHD
Clinical Director, NICHD

As Dr. Porter noted, all involved will need to wait until the children in the trial return back to the National Institutes of Health in Bethesda, Maryland for further testing before the multiple agencies involved will be able to make any additional determinations on how to proceed.  Of course, of utmost concern is that any action will ensure that “first and foremost” ~  the health and safety of all involved is in the forefront.

Thank you to all for their continued expertise, support and involvement in these efforts.

Kind regards,
Nadine

[Feb 25th, 2014 ~ blg]

Update from Genzyme on
Acid Sphingomyelinase Deficiency (ASMD) Development Efforts
February 13th, 2014

Genzyme, a Sanofi company, is pleased to update the Niemann-Pick Disease patient community on the progress of our efforts to develop a potential therapy for acid sphingomyelinase deficiency (ASMD, also known as Niemann-Pick disease Types A and B).

Recently, Dr. Simon Jones, MbChB, presented interim tolerability and safety information from our Phase 1b clinical trial at the WORLD Symposium, held in San Diego, CA.

The title of the presentation was:

An open-label, multicenter, ascending dose study of the tolerability and safety of recombinant human acid sphingomyelinase (rhASM) in patients with ASM deficiency (ASMD). (The abstract is listed under # 112.)

For the full update, visit the Enzyme Replacement Therapy Page

[Feb 20th, 2014 ~ blg]


~Cyclodextrin Update~

“Trials ~ A Desperate Fight to Save Kids & Change Science”
By Amy Dockser Marcus ~ Staff writer for the Wall Street Journal
Dateline:  November 14, 2013

For six years, The Wall Street Journal followed a group of parents and scientists seeking a treatment for a rare and fatal genetic disease that strikes primarily children. Their collaboration accelerated development of a promising drug and, along the way, pushed the boundaries of medical research itself.

Follow this link to learn more about the story associated with Niemann-Pick Disease Type C here:

Trials: A Desperate Fight to Save Kids & Change Science

The members of the National Niemann-Pick Disease Foundation would like to offer a genuine note of thanks and heartfelt gratitude to the many individuals, families, community members, advocacy groups, as well as, esteemed members of the research and scientific community who all came together in a truly collaborative effort to see this process through to a clinical trial.

A sincere note of thanks and appreciation goes out to this articles author, Amy Dockser Marcus, of The Wall Street Journal and her team of photographers, Evan Simon and Melissa Golden, for her unending devotion, dedication and perseverance, not only to the written word on the page which portrays the desperation and heartbreak that our Niemann-Pick Disease Families face at the diagnosis of their loved one, but to know how genuinely Ms. Marcus connected with the children and families she had the opportunity to work with.  She gathered them close, held them in her heart and helped them to build treasured memories.  For that, we are especially indebted.

Last, but certainly not least, are the sweet children and young adults diagnosed with Niemann-Pick Disease, whose families took the courageous step to move outside of their “safe-harbor” comfort zones and moved into the wider community and news media to share their families tragic diagnosis, knowledge, experience and personal sorrow. All of our Niemann-Pick Disease families will be forever grateful to those who braved sharing their heartbreak and personal circumstances for the wider NPD community.

We WILL one day, all stand together, hand-in-hand, and declare that we have Persevered in Our Quest for A Cure!

~ National Niemann-Pick Disease Foundation

[Nov 14th, 2013 ~ blg]

Orphazyme Update - 10/31/2013
Orph001 (rhHSP70) Project Progress

Dear Families and Friends,

The NNPDF Central Office received an update pertaining to the current research and clinical trial work as it relates to Orphazyme and their proposed clinical trial titled: Orph001 (rhHSP70).

Dear Reader,

We would like to update you about the progress of the Orph001 clinical development programme.

With the aim of reaching the highest achievable quality in standards and procedures certain amendments have been introduced into the Orph001 development programme to ensure full dose definition, and high alignment to regulatory recommendations and requirements in Europe and US.

Please, let us give you a short review of our development program and the steps ahead.

Click Here to read the full Press Release

Visit Orphazyme's web site

[Nov 5th, 2013 ~ blg]

Update from Genzyme on Acid Sphingomyelinase Deficiancy (ASMD) Development Efforts

Genzyme, a Sanofi company, is continuing its efforts to develop a potential therapy for acid sphingomyelinase deficiency (ASMD, also known as Niemann-Pick disease Types A and B). The potential treatment is the enzyme replacement therapy recombinant human acid sphingomyelinase (rhASM); it is being evaluated for the treatment of the non-neurological manifestations of ASMD.

To read the full update, please visit the Enzyme Replacement Therapy - Type B page.

We have also learned that Genzyme and Mount Sainai are recruiting new patients for phase1b of the Enzyme replacement therapy.  For more information: Click Here

[May 7th, 2013 blg]

Orphazyme Announces Proposed Clinical Trial
of rhHSP70 for NPC

~ Apr 19th, 2013 ~


Dear NPD Community,

Orphazyme, a Danish biotech company, announced its intention to conduct a trial of rhHSP70 as a therapeutic intervention in NPC disease, at a scientific conference in Italy this week (15th-19th April 2013).

Orphazyme has provided information for patients and families which will be generally available through patient organizations across the world. This information has been issued on the understanding that much has still to be confirmed / agreed by the regulatory authorities, so please be aware that some of the details may change.  View the Orphazyme Slide Presentatio n .

To assist you, we have produced an additional document that summarizes the main points:  View the: Orphazyme Trial Announcement Summary .

In order to facilitate communication further, Orphazyme intends to launch a web page for the trial and to include a “Frequently Asked Questions” section on the page.  As soon as this information is available, we will share it with you. Further information about Orphazyme can be found on their website: http://www.orphazyme.com/

[Apr 19th, 2013 blg]

NIH Clinical Research Trials and You
New Web Site Launched

The NIH recently announced the launch of a new Web site titled NIH Clinical Research Trials and You , geared for those considering participating in a clinical trial.

According to the press release announcing the new site , "Clinical trials are essential for identifying and understanding ways to prevent, diagnose, and treat disease. Research has shown that among the greatest challenges to recruitment of volunteers is the lack of general knowledge about what trials involve, where they are carried out, and who may participate."

This new Web site aims to help potential participants learn about clinical trials and make an informed decision about whether they should take part.  The site includes sections on "The Basics," "Volunteer Stories," "Researcher Stories," "Finding a Trial."  Also, "For Health Care Providers," "Educational Resources," a glossary of terms, and much more.

Visit the new site at http://www.nih.gov/health/clinicaltrials/ to learn more.

[Feb 14, 2012 mem]

"Compassionate Use"
Access to Investigational Drugs

The term "compassionate use" refers to the treatment of a seriously ill patient using a new, unapproved drug when no other treatments are available. Drugs that are being scientifically tested but have not yet been approved by the United States Food and Drug Administration (FDA) are called investigational drugs. Being able to use one of these drugs when you are not in a clinical trial specifically designed to study that drug has many names, but is most commonly referred to as compassionate use.

Given the recent discussions about access to cyclodextrin, we thought you might like to read more about compassionate access to drugs.  Cate Walsh Vockley, Certified Genetic Counselor, prepared this article about compassionate use, including links to additional resources.

[Oct 16, 2009 mem]

New Research Opportunity Comes from Karen Quandt's Family History Study
“Neurodegenerative Disease in Family Members of Patients with Niemann-Pick Disease, Type C”

In 2008 several families affected by Niemann-Pick Disease Type C took part in the above research survey conducted by Karen Quandt, RN, MSN. It is not necessary to have participated in Karen's original study to participate in this new study, but you must meet the study criteria described below.

Karen discussed the findings of the survey with Dr. Ellen Sidransky and Jolie Davis, nurse practitioner, both of whom work at the National Institutes of Health.

Dr Sidransky is Senior Investigator in the National Human Genome Research Institute's Medical Genetics Branch. As part of her research protocol “Studies of Heterogeneity in Patients with Lysosomal Storage Disorders” she is exploring a link between Gaucher disease, a rare lysosomal storage disorder, and a far more common disorder, Parkinson's disease. Dr. Sidransky and her colleagues at other institutions discovered that people with Gaucher disease had more relatives with Parkinson's disease than the general public.

Dr Sidransky is very interested in the results of Karen’s Niemann-Pick Type C survey and she would like to investigate the possible association between NPC and three specific neurodegenerative disorders - Parkinson disease, ALS (Lou Gehrig disease), and early-onset Alzheimer disease (diagnosed before the age of 65). The aim would be to see if the relative with such a neurodegenerative disease also carries an NPC mutation.

Dr. Sidransky states, "The individuals of interest would be NPC families who have undergone genetic testing and know the specific NPC mutation AND who also have a family member with Parkinson disease, ALS, or early-onset Alzheimer disease. We would test the individual who has one of these three disorders for the NPC mutation. They would contact me, I would explain the study, draw a family tree, consent them (if they wished to proceed), and arrange the NPC testing (this would involve a cheek brush test to collect DNA for genetic studies). In those individuals with Alzheimer Disease, I would need to speak with their durable power of attorney (DPA)”.

If you know your specific NPC mutations and have a relative who has ALS, Parkinson disease, or early-onset Alzheimer disease who might be interested in taking part in this study, or if you have additional questions, please contact Dr Sidransky directly at [email protected] or by phone at 301-496-0373.

For more about Dr. Sidransky's work, visit the Latest Research page.

Updated 3/9/2009,7/14/2009 CWV

[Oct 30, 2009 mem]

“The Canadian Chapter of the National Niemann-Pick Disease Foundation (CCNNPDF) does not engage in the practice of medicine. It is not a medical authority nor does it claim to have medical knowledge. This site is an educational service of the Canadian Chapter of the National Niemann-Pick Disease Foundation and is not meant to provide diagnostic or treatment advice. Information contained or suggested on this Web site does not constitute medical advice. For all information related to care, medication or treatment, the CCNNPDF recommends consulting a physician to determine if information presented is applicable. Please review these additional cautions about medical information provided on the Internet.”