Have you had joint replacement surgery?

A new research study at Quinnipiac University, led by our Scientific Advisory Board chair, Carolyn Macica, PhD, is looking into XLH patients' experience with joint replacement surgery. Please note that anyone currently in a clinical trial is NOT eligible for this study.

Here's the official description:

We are seeking men and women aged 18 or older with X-linked hypophosphatemia (XLH) who have had a hip or knee replacement to participate in an online questionnaire in exchange for a Starbucks gift card. The purpose of this questionnaire is to learn more about joint replacements in patients with XLH. With the information gathered, we will be able to educate clinicians about joint replacements in patients with XLH.

Step 1: The first step is to determine if you qualify for the study. If you are a male or female aged 18 years or older diagnosed with XLH by a physician and you have had either a hip or knee replacement more than 6 months ago, you qualify to participate in this study. You may not be involved in any current clinical trials to participate in the study.

Step 2: Next, you will be asked to complete an online questionnaire about your joint replacement(s). It will take about 30 minutes to complete, so please make sure you have enough time to give thought to each of your answers. You will also be asked to sign a medical records release form and provide us with your orthopedic surgeons name and office number, so please make sure you have those available before starting the questionnaire. You will receive a $30 Starbucks gift card if you complete the survey.

Think you qualify? Click the link below to begin the survey:

http://quinnipiacmed.az1.qualtrics.com/jfe/form/SV_6n9bQ8DOWPiITvT

Study HIC#: 6316

Principal Investigator:

Dr. Carolyn M. Macica

Contact Information:

XLHPainStudy@quinnipiac.edu

DISCLAIMER: The XLH Network, Inc. does not endorse or critique specific clinical trials, and does not counsel individual patients either for or against participation in any specific clinical trial. Prospective volunteers should always carefully review the clinical trial's informed consent documentation, and discuss the pros and cons of their participation with trusted advisers, including their health care providers and family members.

Pediatric KRN23 trials update

A recent press release from Ultragenyx Pharmaceutical contains encouraging results from the KRN23 pediatric clinical trials, including this quote from our Scientific Advisory Board member Thomas O. Carpenter, M.D.:

"The recent data from the KRN23 experience in pediatrics are compelling, with sustained improvements in biochemical and radiographic measures beyond those achieved in most patients with standard therapy. Gauging from this response, and the preferences of the patients and families themselves, the drug has great potential to change the treatment paradigm for XLH," commented Tom Carpenter, M.D., the lead investigator in this study.

You can read the whole press release here: http://ir.ultragenyx.com/releasedetail.cfm?ReleaseID=945146

Catching up

There's been so much happening lately, and some topics have been piling up, so here's some short snippets of information to get us all caught up.

First, there's an online survey for research at the University of Rochester (New York) on "Understanding and overcoming obstacles to participation in clinical research for patients with rare diseases." If  you'd like to share your thoughts on the issue, you can complete the survey here: https://redcap.urmc.rochester.edu/redcap/surveys/?s=PE9AWFM48K

For new members who haven't heard about it yet, if you'd like to share your thoughts and experiences on research that's more specific to XLH, you can do the Burden of Illness survey here: https://www.amihealthy.com/custom/ultragenyx/burdenofillness/burdenofillnesshome.aspx?SITE=XLHNETWORK Note that it's now available in a variety of languages: English, French, Portuguese and several versions of Spanish.

And finally, a reminder that the Global Genes Patient Advocacy Summit is happening tomorrow and Friday. If you'd like to watch the livestream to better understand what you can do to advocate for yourself, and what the Network's board is doing on your behalf, you can register here: https://globalgenes.org/2015summit/ Our president, Becky Mock, will be attending the summit, and we hope to have some pictures at our official Facebook page, facebook.com/xlhnetwork

One of the speakers is Pat Furlong, the CEO of Parent Project Muscular Dystrophy (Thursday, 9 a.m. California time, noon Eastern time), and I (Gin Jones) can tell you she's amazingly inspiring. She spoke at a workshop I attended last week, and I'm still thinking about some of the things she said, like how patient advocates need to find innovative ways to "quantify the patients'/caretakers' tears," putting the suffering into a format that researchers and funders and the FDA can understand.

KRN23 adult clinical trials

The Phase 3 KRN23 clinical trials for adults with XLH are set to begin in October. The announcement indicates that they're not yet recruiting, but we'll  update when we find out that recruiting has begun.

In the meantime, if you're considering participating in the trials, you can review the inclusion/exclusion criteria (available here: https://clinicaltrials.gov/ct2/show/NCT02526160?term=XLH&rank=1 ) and discuss your participation with trusted advisers.

You might also find the following sites useful for background information on participating in clinical trials and questions to ask:

http://www.nih.gov/health/clinicaltrials/basics.htm      

https://www.ciscrp.org/education-center/

Board member Kathy Buchanan, who has extensive experience as a clinical research nurse and is a certified clinical research coordinator, suggests that anyone considering participation in a trial should read all of the documents carefully, especially the consent form. Some questions that ought to be addressed by the paperwork, but that you may wish to ask about are: 1) how much time your involvement will require, 2) how often you'll be required to travel, 3) how often bloodwork and other lab work will be done, 4) what side effects may occur and how/when to report them. Finally, if payment is offered for participation, make sure you understand when the monies will be paid (e.g., at the end of the study or at shorter intervals).

Note that, as always, the XLH Network, Inc. does not endorse or critique specific clinical trials, and does not counsel individual patients either for or against participation in any specific clinical trial. Prospective volunteers should always carefully review the clinical trial's informed consent documentation, and discuss the pros and cons of their participation with trusted advisers, including their health care providers and family members.

Expanded pediatric clinical trials

The expanded pediatric clinical trials for KRN23 are recruiting NOW!

Here's the link to clinicaltrials.gov: https://www.clinicaltrials.gov/ct2/show/NCT02163577

Note that this is happening in a number of countries, not just in the U.S. There are locations in France, the Netherlands and the UK.

As always, The XLH Network, Inc. does not endorse or critique specific clinical trials, and does not counsel individual patients either for or against participation in any specific clinical trial. Prospective volunteers should always carefully review the clinical trial's informed consent documentation, and discuss the pros and cons of their participation with trusted advisors, including their health care providers and family members.

The tooth fairy is calling

We need teeth!

Don't worry, we don't want you to pull out healthy ones and send them to us, but if you're an adult XLH patient who's having a tooth extracted in the next few weeks, we could use it for research.

One of our SAB members, Carolyn Macica, PhD, is researching the mineralization of our teeth, which ought to provide useful information about mineralization in our bones. She has already studied a number of baby teeth, which are relatively easy to get from the tooth fairy (although she could use some more if you have them to send), but adult teeth are more difficult to come by.

So, if you're planning to have a tooth pulled soon (or perhaps your young-adult child is having wisdom teeth pulled), please consider asking the oral surgeon to keep the teeth, so you can send them to Dr. Macica for research. Or if you kept teeth that were pulled in the past, those can be used for research too.

Dr. Macica needs them ASAP, preferably by the end of February, so if you're planning to send them after that, please check the Network's website where we list clinical trials (http://xlhnetwork.org/index.php/what-is-xlh/clinical-trials/) to see if she still needs more teeth.

Here's the address to send the teeth:
 Dr. Carolyn M. Macica
Quinnipiac University
Frank H. Netter School of Medicine MNH 311H
275 Mt. Carmel Avenue Hamden, CT 06518-1908

She would be happy to reimburse the North American postage cost, if you include a note with the amount and your address.

KRN23 study in Japan and Korea

Researchers are looking for adult XLH patients in Japan and Korea, to participate in a study involving KRN23, the antibody being developed to reduce excess FGF23, which appears to be at least part of the root cause of XLH patients' symptoms.

You can read more about it, and get contact information, here: http://clinicaltrials.gov/ct2/show/NCT02181764?term=xlh&rank=8

The XLH Network, Inc. does not endorse or critique specific clinical trials, and does not counsel individual patients either for or against participation in any specific clinical trial. Prospective volunteers should always carefully review the clinical trial's informed consent documentation, and discuss the pros and cons of their participation with trusted advisors, including their health care providers and family members.

Latest KRN23 trial results

If you've been following us on Facebook (https://www.facebook.com/xlhnetwork), you've seen our pictures from the ICE-ENDO conference this week.

The big news coming out of the conference, at least for XLH patients, is the announcement of the latest KRN23 clinical trial results. KRN23 is an antibody developed to counteract the excessive FGF23 that is at least part of the process of XLH patients' phosphate wasting. KRN23 is being developed in collaboration between two pharmaceutical companies, Kyowa Hakko Kirin and Ultragenyx.

The CEO of Ultragenyx, Emil Kakkis, M.D., PhD., is quoted by MarketWatch: "Based on observed improvements in phosphate metabolism, bone remodeling markers, and certain quality of life measures, we are encouraged by the potential for KRN23 to treat the underlying cause of bone disease in both adult and pediatric patients with XLH."

You can read more about the results here. As the news report indicates, pediatric clinical trials are starting now (find out more here), and additional adult clinical trials are in the works. Stay tuned, here and at Facebook, for updates on those trials.

Pediatric clinical trial for KRN23

The pediatric (ages 5 to 12) clinical trial for KRN23 (the antibody developed to control FGF23, which is at least part of the root cause of XLH patient's phosphorus wasting) is about to start.

Details are at clinicaltrials.gov: http://clinicaltrials.gov/ct2/show/NCT02163577?term=krn23&rank=3

Note that while the listing indicates "not yet recruiting," it is NOT too soon to contact the nearest of the locations participating in the study. This is a very limited study, with only thirty participants worldwide, so the slots will be filled quickly.

The XLH Network, Inc. does not endorse or critique specific clinical trials, and does not counsel individual patients either for or against participation in any specific clinical trial. Prospective volunteers should always carefully review the clinical trial's informed consent documentation and protocol, and discuss the pros and cons of their participation with trusted advisors, including their health care providers and family members. The NIH website offers some good questions to consider while deciding whether to enroll in a clinical trial.

Cinacalcet study

Elevated parathyroid hormone (PTH) levels, or "hyperparathyroidism" is a common symptom for many XLH patients. A drug known as Cinacalcet, which is generally used for the hyperparathyroidism of chronic kidney disease patients, is sometimes prescribed to XLH patients to lower our PTH levels.

Since the use of the drug by XLH patients wasn't officially studied prior to the drug's approval, it's considered an "off-label" use, which raises a number of issues. First, insurance companies can be reluctant to pay for off-label use. Second, not all doctors treating XLH patients even know that it's an off-label use. Third, and most important, scientists don't even know for sure that it's effective on our form of parathyroidism, what an optimal dose is, or whether it might also help reduce our phosphorus wasting.

Dr. Rachel Gafni, at the National Institutes of Health, has been studying the use of Cinacalcet specifically in XLH patients. Until recently, the study was only open to patients living within a fairly small radius of D.C. The study has been expanded recently to include patients from all over the U.S., with travel expenses to be reimbursed according to NIH guidelines.

Information provided by the principal investigator, with contact information:

• NIH Research Study: Open-label Dose-titration Study of the Tolerability and Efficacy of Cinacalcet to Treat Fibroblast Growth Factor 23 (FGF23)-mediated Hypophosphatemia
• Principal Investigator: Dr. Rachel Gafni, MD
• Sponsoring Institute: Craniofacial and Skeletal Diseases Branch, NIDCR, National Institutes of Health
• The purpose of this study is to see how treatment with a drug called cinacalcet affects people with low blood phosphorus (hypophosphatemia) caused by hypophosphatemic rickets or tumor-induced osteomalacia. Studies have suggested that cinacalcet may decrease phosphorus loss by the kidneys in these disorders. If the cinacalcet works, the blood level of phosphorus may be higher. This could result in patients needing less phosphorus medication. It may also help the bones become stronger.
• This study will help us figure out the best dose of cinacalcet and how many times a day it should be taken.  Individuals who qualify for the study will take cinacalcet in addition to vitamin D and phosphorus.  Many of the study visits will be at the NIH Clinical Center in Bethesda, Maryland. Some of the blood and urine tests may be done at a facility that is closer to the patient’s home. There will be up to 3 inpatient visits and a number of outpatient clinic and lab visits. 
• Once cinacalcet therapy is started, there will be 3 - 5 visits with a physician every 3 weeks over a 4- to 7-month period. During the NIH visits, participants will undergo several assessments, which may include a dental evaluation, blood tests, urine tests, x-rays, and questionnaires. Patients will be paid for participation in this study and will be reimbursed for travel expenses, according to NIH policy. You may be eligible if you are between 18 and 70 years of age and have been diagnosed with low blood phosphorus. For more information, please contact the NIH Patient Recruitment and Public Liaison hotline at 1-800-411-1222 or prpl@cc.nih.gov.

The XLH Network, Inc. does not endorse or critique specific clinical trials, and does not counsel individual patients either for or against participation in any specific clinical trial. Prospective volunteers should always carefully review the clinical trial's informed consent documentation and protocol, and discuss the pros and cons of their participation with trusted advisers, including their health care providers and family members. The NIH website (clinicaltrials.gov) offers some good questions to consider while deciding whether to enroll in a clinical trial.

Kyowa Shares KRN23 Data

Announcement of Results from a Single Dose Phase 1 Study of a Human Monoclonal Anti-FGF23 Antibody (KRN23) in X-linked Hypophosphatemia in Adults

Tokyo, Japan, October 7, 2013 -- Kyowa Hakko Kirin Co., Ltd. (Tokyo; 4151, President and CEO: Nobuo Hanai, "Kyowa Hakko Kirin") announced that results from a first-in-human, single dose Phase 1 study of a human monoclonal anti-FGF23 antibody (KRN23) in X-linked hypophosphatemia (XLH) in adults were presented at the American Society of Bone Mineralization Research (ASBMR) 2013 Annual Meeting on October 6, 2013. A randomized, double-blind, placebo-controlled, Phase I study (US-02) was conducted to assess its safety, tolerability, pharmacokinetics and pharmacodynamics in adult patients with XLH. Thirty-eight adults with XLH were randomized to receive single doses of KRN23 or placebo via intravenous (IV) (0.003 to 0.3 mg/kg) or subcutaneous (SC) (0.1 to 1.0 mg/kg) routes.

Data were presented by Thomas Carpenter, MD, Yale University at the ASBMR 2013 Annual Meeting. The study showed single doses of either IV or SC KRN23 increased serum phosphate level compared to placebo for higher doses (p<0.01). Peak serum phosphate effects occurred later with SC (8-15 days) than with IV dosing (0.5-4 days). Duration of effect on phosphate was dose-related, greater with SC than IV, and persisted beyond 29 days with SC. Increases in renal reabsorption of phosphate and 1,25 dihydroxyvitamin D were observed. No meaningful changes in serum calcium, serum parathyroid hormone, and urinary calcium excretion occurred. The majority of adverse events were mild, and there were no serious adverse events, and no changes in safety biochemistries, electrocardiograms, or renal sonograms. No patient developed anti-KRN23 antibodies. Single dose administration of KRN23 was safe and well-tolerated.

Kyowa Hakko Kirin has a collaboration and license agreement with Ultragenyx Pharmaceutical Inc. ("Ultragenyx") to jointly develop and commercialize KRN23. Kyowa Hakko Kirin and Ultragenyx plan to continue the development of KRN23 in adult XLH patients while initiating a pediatric XLH program in 2014.

About KRN23 and FGF23
KRN23 is a recombinant fully human monoclonal IgG1 antibody discovered by KHK and being developed to treat X-linked hypophosphatemia (XLH). KRN23 is designed to bind to and thereby reduce the biologic activity of fibroblast growth factor 23 (FGF23). FGF23 is a hormone that promotes phosphate excretion by the kidney and suppresses vitamin D production. FGF23 also reduces the expression of the enzyme that is required to synthesize a hormone that normally increases renal tubular absorption of both phosphate and calcium. Therefore, FGF23 induces profound reductions in serum phosphate levels. Phosphate wasting in XLH is caused by excessive levels and activity of FGF23.

About X-linked Hypophosphatemia (XLH)
XLH is a disorder of phosphate metabolism caused by phosphate wasting in the urine leading to severe hypophosphatemia. XLH is the most common heritable form of rickets that is inherited as an X-linked dominant trait affecting both males and females, though the disease in males by some reports may be more severe. XLH is a distinctive bone disease characterized by inadequate mineralization of bone that leads to a spectrum of abnormalities, including progressive bowing of the leg, osteomalacia, bone pain, waddling gait, short stature, gross motor impairment, muscle weakness, osteopenia, frequent/poorly healing microfractures, spinal stenosis and osteoarthritis.

Most patients are managed using oral phosphate replacement and vitamin D (calcitriol) therapy, which is poorly tolerated and only partially effective at restoring bone physiology and growth. Current treatment with oral phosphate requires extremely close monitoring and can result in complications such as secondary hyperparathyroidism, hypercalciuria, hypercalcemia and nephrocalcinosis. XLH was originally called vitamin D-resistant rickets, because doses of vitamin D effective for the treatment of vitamin D-deficient nutritional rickets did not have an impact on phosphate levels in these patients.

About Ultragenyx Pharmaceutical Inc.
Ultragenyx is a privately held, clinical-stage biotechnology company committed to bringing to market life-transforming therapeutics for patients with rare and ultra-rare metabolic genetic diseases. Founded in 2010, the company is rapidly building a diverse portfolio of product candidates with the potential to address diseases for which the unmet medical need is high, the biology for treatment is clear, and for which there are no effective treatments.

The company is led by a management team experienced in the development and commercialization of rare disease therapeutics. Ultragenyx's strategy is predicated upon time and cost-efficient drug development, with the goal of delivering safe and effective therapies to patients with the utmost urgency.
For more information on Ultragenyx, please visit the company's website atwww.ultragenyx.com.

Contact:
Kyowa Hakko Kirin
Media Contact:
+81-3-3282-1903

New NIH Research Study

NIH Research Study: Open-label Dose-titration Study of the Tolerability and Efficacy of Cinacalcet to Treat Fibroblast Growth Factor 23 (FGF23)-mediated Hypophosphatemia
Principal Investigator: Dr. Rachel Gafni, MD
Sponsoring Institute: Craniofacial and Skeletal Diseases Branch, NIDCR, National Institutes of Health

The purpose of this study is to see how treatment with a drug called cinacalcet affects people with low blood phosphorus (hypophosphatemia) caused by hypophosphatemic rickets or tumor-induced osteomalacia.  Studies have suggested that cinacalcet may decrease phosphorus loss by the kidneys in these disorders.  If the cinacalcet works, the blood level of phosphorus may be higher.  This could result in patients needing less phosphorus medication.  It may also help the bones become stronger. 

This study will help us figure out the best dose of cinacalcet and how many times a day it should be taken.   Individuals who qualify for the study will take cinacalcet in addition to vitamin D and phosphorus.   All study visits will be at the NIH Clinical Center in Bethesda, Maryland.  There will be up to 3 inpatient visits and several outpatient clinic and lab visits. Once cinacalcet therapy is started, there will be 3 - 5 visits with a physician every 3 weeks over a 4- to 7-month period.  During the NIH visits, participants will undergo several assessments, which may include a dental evaluation, blood tests, urine tests, x-rays, and questionnaires.  Patients will be paid for participation in this study.  You may be eligible if you are between 18 and 70 years of age and have been diagnosed with low blood phosphorus.  For more information, please contact the NIH Patient Recruitment and Public Liaison hotline at 1-800-411-1222 or prpl@cc.nih.gov.

New Clinical Study at Yale

Yale is currently seeking participants for a new study researching the "Use of Nasal Calcitonin to Suppress FGF23 in X-linked Hypophosphatemia".   Please see the flyer below for details.

Add caption

Do You Have X-Linked Hypophosphatemia (XLH)?

A clinical trial is being conducted at several research centers to determine if an investigational agent from Kyowa Hakko Kirin Pharma, Inc. improves the health of adult patients by alleviating the complications associated with XLH.

Eligible participants will be provided study treatment at no charge and may receive compensation for their involvement.

To be eligible for this study you must:

• Be at least 18 years of age;
• Have been diagnosed with XLH; and
• Agree not to change diet or exercise routine for the duration of the study.

Phase I is a double-blind, randomized, placebo-controlled, single-dose, dose-escalation study of KRN23 in X-linked Hypophosphatemia. This first phase is intended to assess the safety and tolerability of KRN23 after a single intravenous or subcutaneous administration in XLH patients.

Phase II is a non-randomized, open-label study intended to assess the safety and efficacy of repeated doses of KRN23 administered subcutaneously in adult subjects with X-Linked Hypophosphatemia (XLH).

Contact any of the participating study centers below for further information.

United States, California
University of California, San Francisco Medical Center	Recruiting
San Francisco, California, United States, 94143
Contact: Stephanie Lamp     415-476-9657     lemps@peds.ucsf.edu
Principal Investigator: Anthony A Portale, MD
United States, Connecticut
Yale University School of Medicine	Recruiting
New Haven, Connecticut, United States, 06520
Contact: Elizabeth Olear, MS, MA     203-785-3759     Elizabeth.olear@yale.edu
Contact: Rebecca Sullivan, MS, RD     203-737-1656     becky.sullivan@yale.edu
Principal Investigator: Thomas O. Carpenter, M.D.
United States, Indiana
Clinical Research Center, Indiana University School of Medicine	Recruiting
Indianapolis, Indiana, United States, 46202-5250
Contact: Connie Sullivan, RN, CCRC     317-944-8431     csulliv1@iupui.edu
Principal Investigator: Munro Peacock, MB
United States, North Carolina
Duke Clinical Research Unit	Recruiting
Durham, North Carolina, United States, 27710
Contact: Margaret Stewart, RN     919-668-0186     margaret.a.stewart@duke.edu
Principal Investigator: Thomas J. Weber, MD
United States, Texas
University of Texas Health Science Center at Houston	Recruiting
Houston, Texas, United States, 77030
Contact: Mary D. Ruppe, MD     713-500-6901     Mary.Ruppe@uth.tmc.edu
Principal Investigator: Mary D. Ruppe, MD
Canada, Quebec
Shriners Hospital for Children - Canada	Recruiting
1529 Cedar, Montréal, Quebec, Canada, H3G 1A6
Contact: Michaela Durigova, PhD     514-282-7158     mdurigova@shriners.mcgill.ca
Principal Investigator: Francis H. Glorieux, OC, MD, PhD

You can also find information about this clinical trial by going tohttp://www.clinicaltrials.gov/ and searching for "KRN23". Before deciding to participate in a research study, you may want to go to http://www.clinicaltrials.gov/ and read "Understanding Clinical Trials". As always it is a good idea to confer with your doctor and/or health care professionals before entering a trial.