In this 1-hour and 7-minute video, FPWR Executive Director Susan Hedstrom presents an overview of current and upcoming PWS clinical trials, and trial representatives provide brief presentations on specific trials.
Click below to watch the video. If you're short on time, scroll down for timestamps to find the portions you're most interested in.
Presentation Summary With Timestamps
0:05 FPWR Executive Director Susan Hedstrom, presents PWS Clinical Trials Panel
- Introduction: This session will introduce PWS families to ways that they can get involved to accelerate research.
- Studies that are currently enrolling or will be recruiting soon will be giving brief presentations so parents in the community can have a better understanding of what opportunities are available to them.
- Participation in a clinical trial is an individual decision that has to be made with a doctor as well as family members.
1:45 Steps of Drug Development Process - Theresa Strong, Ph.D.
- Clinical trials for new drugs have three phases.
- First study in humans
- Doses escalate to the doses where you see an effect and where side effects appear
- Researchers are assessing the safety, tolerability, and how it moves through the body
- Phase 1: 10-20 volunteers
- Phase 2: 10-50 volunteers (rare disease)
- Assess how well the drug works (efficacy), expand safety assessments, more extensive mechanism of action, and pharmacological properties
- Determine if the drug has biological activity or effect
- Phase 3: Approximately 100 volunteers
- Randomized, placebo-controlled, multicenter
- Longer exposure to the drug
- Determine if the therapy is effective in comparison to the “current standard.” Does it have clinical value? Do clinical benefits outweigh the risk?
- Trial must reach pre-determined endpoints (with FDA)
5:00 Challenges
- Number one reason that clinical trials are delayed or not completed is due to an insufficient number of participants.
- Ask everyone to consider participating in a clinical trial for PWS.
5:47 Risks and Benefits
- Benefits:
- Early access to new, potentially effective treatment
- Build a clinical relationship with PWS experts
- Receive excellent medical care
- Travel cost reimbursement
- Help community get answers about whether a new drug will work in PWS, and learn if it benefits your loved one
- Risks:
- May require a significant time investment
- Drug may not work
- Full risks of the drug may not be known
6:57 Protections for Study Participants
- Reviews all information in the Investigational New Drug application to decide if the study can start
- Reviews all serious adverse events over the course of the study
- Can place an immediate “clinical hold” if safety concerns arise
- Study Investigator and team
- Familiar with drug characteristics
- Responsible for safety monitoring and reporting
- Institutional Review Board (IR) at the clinical trial site
- Reviews and approves/monitors biomedical research that involves human subjects
- Protects the rights of research participants
- Reviews and approves informed consent documents
- Data Safety Monitoring Board
- An independent group of experts who review safety and efficacy data during the trial
7:48 Should I Enroll My Loved One in a Clinical Trial?
- Learn about upcoming trials and find out which ones your loved one with PWS might be eligible for.
- Discuss with your medical team/doctor:
- Questions about logistics (time, procedures, travel reimbursements)
- Have an in-depth discussion of potential benefits and safety risks, and what to look for, with the Study Coordinator and study physician.
- Make the decision that is right for you and your loved one with PWS.
- Check the FPWR website and sign up for newsletters to learn about trials.
10:30 Mark Pirner, Chief Medical Officer, ConSynance Therapeutics
- A clinical stage biopharma focusing on rare CNS diseases
- Pirner has a son with autism who is now in grad school, so he is one of the families watching their kids breaking through barriers
- Loves watching FPWR with its passion for improving the lives of kids with PWS
- ConSynance is a startup, a shoestring-level company, all about developing breakthrough medications
- Pirner is an endocrinologist who has worked in addiction, Parkinson’s, and obesity.
- The drug that they are planning to investigate is a CSTI-500 Triple Reuptake Inhibitor (TRI) that they feel is potentially idea for PWS
- Increase all three monoamines (serotonin, dopamine, and norepinephrine) in the brain.
- Has the potential to address both hyperphagia and temper outbursts in people with PWS.
- Prior Phase 1 single and multiple dose studies have been conducted in healthy volunteers
- First CSTI-500 Phase 1 study in PWS patients planned to start enrollment in October 2022 at Vanderbilt University, in Nashville, Tennessee. Study will enroll male and female PWS patients, 13-50 years of age, and test a single 10 mg dose.
- Brand new drug, so they have to go through all the safety protocols before moving to Phase 2.
- Find at clinicaltrials.gov: NCT05504395
18:50 Andreas Niethammer, Chief Medical Officer, Aardvark Therapeutics
- Aardvark is a privately held company based in San Diego, focusing on metabolic disorders and inflammatory diseases.
- Also targeting PWS and SYS
- Have an open study for Oral ARD101
- A novel class of drug
- It is a bitter agonist, one of the most bitter substances known to man
- If you taste it, it would make you miserable.
- They reformulated it so that people can take it without tasting it, and so that it stays in your gut.
- It has a systemic effect that is important. Have seen positive effects in models of overweight, skin infections, arthritis, pneumonia.
- By working in the gut, it is likely to be combinable with other drugs.
- By releasing this bitter substance into the gut, hormones are released that may modulate inflammation.
- Metabolic effects: normalizing blood glucose, insulin, LDL cholesterol, reduced food intake, potentially leading to body weight modulation.
- Single Arm, Open Label Study
- Primary end point: safety
- Secondary end point: hyperphagia, body weight
- Exploratory analyses: body composition, waist circumference, body fat, BMI, blood lipids, insulin resistance, psychiatric status, change in metabolic serum markers
- Eligibility Criteria
- Male and female, ages 17-65 years, with confirmed PWS
- Well-controlled blood pressure
- HbA1C<7.5% not being managed with insulin
- Fasting plasma glucose<140 mg/dL
- Stable body weight for about 2 months prior to enrollment
- Commonly used medications are allowed to be continued
30:30 Borbola Eva Szepes, MD, Early Phase Clinical Project Team Lead representing Gedeon Richter Plc.
- Represents an ongoing Phase 2 clinical trial in adults with PWS: KITE-PWS, an investigational drug that may help to control appetite
- Gedeon is based in Hungary; a 120-year-old company that produces more than 200 drugs, is present in 40 countries, and has 12,000 employees around the world.
- The drug they are investigating is RGH-706, an experimental drug that blocks a hormone called melanin-concentrating hormone (MCH)
- When MCH attaches to specific receptors in the brain it increases the desire to eat.
- RGH-706 aims to be the first MCH blocker studied in people with PWS.
- KITE-PWS will help investigators know if the drug is safe and effective in blocking MCH and reducing appetite in people with PWS.
- Primary goal is to see a decrease in hyperphagia.
- To measure hyperphagia, they are using the Hyperphagia for Clinical Trials questionnaire, the gold-standard questionnaire.
- The questionnaire is a caregiver-reported outcome, so active participation of caregivers and parents is just as important as people with PWS.
- Will also gather information about the pharmacokinetic properties, the effect on body weight composition, and caregiver burden.
- Study is a big endeavor with 25 research sites (7 sites in the US) in 5 countries.
- Study has two parts(people can only enter one study part):
- 30 days screening period
- 6 weeks study treatment
- 11 weeks follow-up period
- Part A: 60 people with PWS
- Part B: 200 people with PWS
- 30 days screening period
- 15 weeks study treatment period
- 2 weeks follow up period
- Procedures include standard weight measurements, waist circumference, vital stats, asking about the symptoms of the participants and the caregivers.
- Need primary caregiver to accompany the person participating.
- Participants will need to be fasting for blood draws (no food or drink aside from water for 10 hours before visit).
- Participants are compensated for travel expenses, out-of-pocket expenses, and a stipend.
- Who can be in the study?
- People with genetic diagnosis of PWS
- At least 17 years old
- Body weight >88 lbs. and <450 lbs.
- Stable body weight for past 3 months
- Have a consistent and reliable caregiver who can track changes in hyperphagia, mood, health, and behavior.
- Caregiver must spend at least 4 waking hours per day with participant.
- No uncontrolled diabetes or diabetes that requires insulin.
- Possible risks:
- RGH-706 might not help symptoms
- Side effects
- Discomfort and time commitment related to study procedures
- Possible benefits:
- Drug might help symptoms
- Receive regular health check-ups
- Help doctors learn about RGH-706, which could help others with PWS in the future.
- Learn about this trial at clinicaltrials.gov/ct2/show/NCT05322096
42:10 Dr. Deepan Singh, MD, Guanfacine
- Dr. Singh is a clinician who has worked primarily with people with PWS for more than 8 years.
- Believes we need more people who treat just PWS.
- PWS is unique in its neurobiology, and there are risks involved with many medicines.
- Surveys show that behavioral problems are sometimes the most debilitating feature in PWS.
- Irritability, anger, and outburst are problems that have FDA-approved medicines, but they don’t always work well for patients with PWS, or they tend to have more side effects because they are sensitive to them.
- As a clinician, he is looking for what to give a patient who can’t tolerate a stimulant, an antipsychotic, or an SSRI because they might cause a manic episode or more severe symptoms.
- Guanfacine is a very old medicine. It comes in an extended release form.
- It is a mild blood pressure reducing medicine, which has been approved for many years for ADHD.
- It is the only medicine that bypasses or does not affect the core sort of neurotransmitters.
- It works on the synaptic receptor, and increases the activity of the front brain without messing up the rest of the system.
- He has been prescribing it for many years.
- Many of his patients have benefited from it, and now he wants to prove it.
- Participating in clinical trials is important, and Dr. Singh needs participants to run the trial.
- Participants need to come to Brooklyn, NY, three times.
- Looking for participants between the ages of 6 and 36, should have some form of impulsivity: skin picking, rectal picking, or harming themselves in some other way.
- They have some form of aggression; could mean caregivers are walking on eggshells.
- Because the medicine is available on the market, the last 8 weeks of the trial, Dr. Singh contacts pediatricians or psychiatrists to educate them on the medicine if the participant is doing well on it.
50:15 Q & A
Learn more about PWS clinical trials.
