Prader-Willi SyndromePhase 2/3ZEPHYRNCT03790865
Effects of Livoletide (AZP-531) on Food-related Behaviors in Patients With Prader-Willi Syndrome
A Phase 2/3 study testing Livoletide in people with Prader-Willi Syndrome and Hyperphagia, run by Millendo Therapeutics SAS at 37 sites in 8 countries.
Trial summary
This Phase 2b/3 double-blind, placebo-controlled study will evaluate the safety, tolerability, and effects of livoletide on food-related behaviors in patients with Prader-Willi Syndrome (PWS). Read more about this study
- Who is it for?
- Ages 4 to 65 years
- Conditions the study is for
- Prader-Willi Syndrome, Hyperphagia
- What is being tested?
- Livoletide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 158 participants
- Where
- 37 sitesin 8 countries
- Study dates
- 25 Mar 2019to 25 May 2020
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Confirmed genetic diagnosis of PWS
- Evidence of increased appetite or hyperphagia
- Patient must have a single primary caregiver who should be available for certain durations of the study
- BMI ≤ 65 kg/m2
- Growth hormone treatment permitted if doses have been stable for at least 1 month prior to screening
Who cannot join
- History of chronic liver disease
- Type 1 diabetes mellitus
- HbA1c > 10%
- Body weight <20 kg
Trial locations and contacts
37 sites in 8 countries.
37 sites in 8 countries
United States15 sites
University of Michigan
Ann Arbor, Michigan, 48109
Johns Hopkins University
Baltimore, Maryland, 21287
University of Alabama at Birmingham
Birmingham, Alabama, 35233
Boston Children's Hospital
Boston, Massachusetts, 02215
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
Children's Hospital Colorado
Denver, Colorado, 80045
Baylor College of Medicine
Houston, Texas, 77030
University of Kansas Medical Center
Kansas City, Kansas, 66160
Winthrop University Hospital
Mineola, New York, 11501
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
New York Presbyterian Morgan Stanley Children's Hospital
New York, New York, 10032
University of California - Irvine Medical Center
Orange, California, 92868
Children's Hospitals and Clinics of Minnesota-Minneapolis
Saint Paul, Minnesota, 55102
Rady Children's Hospital - San Diego
San Diego, California, 92123
Seattle Children's Hospital
Seattle, Washington, 98105
France6 sites
Centre Hospitalier Universitaire d'Angers
Angers, 49100
CHU Lyon - Hopital Femmes Mere Enfant
Bron, 69677
Hospital Pitie Salpetriere
Paris, 75013
Hopital Necker-Enfants Malades
Paris, 75015
CHU de Toulouse - Hospital Rangueil
Toulouse, 31059
CHU de Toulouse - Hopital des Enfants
Toulouse
Australia4 sites
Royal Prince Alfred Hospital
Camperdown, 2050
Austin Health
Melbourne, 3084
Perth Children's Hospital
Nedlands, 6009
The Childrens Hospital at Westmead
Westmead, 2145
Spain4 sites
Hospital General Universitario de Alicante
Alicante, 03010
Hospital de Cruces
Barakaldo, 48903
Hospital Sant Joan de Deu
Barcelona, 08950
Corporacio Sanitaria Parc Tauli - Hospital de Sabadell
Sabadell, 08208
United Kingdom3 sites
NHS Tayside
Dundee, DD1 9SY
Chelsea and Westminster Hospital
London, SW109NH
Imperial College London
London, W12 0NN
Italy2 sites
Azienda Ospedaliera Universitaria Federico II
Naples, 80131
Ospedale Pediatrico Bambino Gesù
Roma, 00165
Netherlands2 sites
Erasmus University Medical Center
Rotterdam, 3015
Stichting Kind en Groei
Rotterdam, 3016
About this study
Official title: A Phase 2b/3 Study to Evaluate the Safety, Tolerability, and Effects of Livoletide (AZP-531), an Unacylated Ghrelin Analogue, on Food-related Behaviors in Patients With Prader-Willi Syndrome
This Phase 2b/3 double-blind, placebo-controlled study will evaluate the safety, tolerability, and effects of livoletide on food-related behaviors in patients with Prader-Willi Syndrome (PWS).
Read the detailed description
The protocol includes 2 consecutive parts:
- The first part is a Phase 2b dose-response study consisting of a 3-month double-blind, placebo-controlled Core Period followed by a 9-month Extension Period.
- The second part is a Phase 3 study consisting of a 6-month double-blind, placebo-controlled Core Period followed by a 6-month Extension Period. Phase 3 may be initiated following review of safety and efficacy results at the completion of the Phase 2b Core Period.
A total of approximately 50 patients per group (8 to 65 years of age) will be randomized (approximately 150 patients in total). In addition to this cohort of 150 patients, a separate cohort of patients 4 to 7 years of age will also be randomized.
Note: The 8-65 year old cohort has been fully enrolled. Enrollment into the 4-7 year age cohort remains ongoing.
- Conditions
- Prader-Willi Syndrome, Hyperphagia
- Being tested
- Livoletide, Placebo
- Keywords
- Prader-Willi Syndrome, PWS
- Medical subject headings
- Prader-Willi Syndrome, Hyperphagia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LivoletideDrug
Also called AZP-531
Daily subcutaneous injection
PlaceboDrug
Daily subcutaneous injection
| Study group | Role | What they receive |
|---|---|---|
| Low-Dose Livoletide | Experimental | Daily subcutaneous injection of ~ 60 mcg/kg for 3 month double-blind core period and 9 month open label extension period. Receives: Drug: Livoletide |
| High-Dose Livoletide | Experimental | Daily subcutaneous injection of ~120 mcg/kg for 3 month double-blind core period and 9 month open label extension period. Receives: Drug: Livoletide |
| Placebo | Placebo comparator | Daily subcutaneous injection of 0.9% NaCl for the 3 month double-blind core period and then low-dose or high-dose livoletide for 9 month open label extension period. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Hyperphagia and Food-related Behaviors (Hyperphagia Questionnaire for Clinical Trials; HQ-CT)
Change from baseline to the end of the 3-month Core Period for HQ-CT total score. The HQ-CT score range is 0 to 36 where the higher score represents more severe abnormal food related behaviors.
Measured: Baseline to month 3
Secondary outcomes (3)
Percentage Change From Baseline to Month 3 in Total Body Fat Mass in Patients Eight to 65 Years of Age Defined as Overweight/Obese
Total body fat mass was assessed using dual energy X-ray absorptiometry (DXA) scan. DXAs were conducted at each local facility using standardized procedures and settings.
Overweight/obese patients were defined as follows:
- patients ≥18 years of age: BMI ≥27 kg/m2
- patients 4-17 years of age: BMI ≥90th percentile for the same age and sex
Measured: Baseline to month 3
Change From Baseline to Month 3 in Waist Circumference in Patients Eight to 65 Years of Age Defined as Overweight/Obese
The waist circumference was measured in fasting condition at the superior border of iliac crest, according to recommendations from the Anthropometry Procedures Manual of the National Health and Nutrition Examination Survey, Revised 2007.
Overweight/obese patients were defined as follows:
- patients ≥18 years of age: BMI ≥27 kg/m2
- patients 4-17 years of age: BMI ≥90th percentile for the same age and sex
Measured: Baseline to month 3
Percentage Change From Baseline to Month 3 in Body Weight in Patients Eight to 65 Years of Age Defined as Overweight/Obese
Patients were weighed in fasting condition, clothed (underwear, light gown or light clothing), without footwear or heavy jewelry, using a calibrated scale. The same scale should be used throughout the study if possible. The conditions under which patients are weighed should be kept consistent if possible.
Overweight/obese patients were defined as follows:
- patients ≥18 years of age: BMI ≥27 kg/m2
- patients 4-17 years of age: BMI ≥90th percentile for the same age and sex
Measured: Baseline to month 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jan 2019
- Study start25 Mar 2019
- Primary completion26 Feb 2020
- Study completion25 May 2020
Why it stopped: Livoletide did not result in a statistically significant improvement in hyperphagia and food-related behaviors
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Prader-Willi SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 158 participants (actual)
Sponsor and investigators
- Lead sponsor
- Millendo Therapeutics SAS
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03790865
- Sponsor's protocol ID
- AZP01-CLI-003
- Acronym
- ZEPHYR
- Status last verified
- Feb 2021
- First submitted
- 28 Dec 2018
- Last updated
- 17 Feb 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2b/3 Study to Evaluate the Safety, Tolerability, and Effects of Livoletide (AZP-531), an Unacylated Ghrelin Analogue, on Food-related Behaviors in Patients With Prader-Willi Syndrome
- ClinicalTrials.gov ID
- NCT03790865
- Acronym / sponsor ID
- ZEPHYR / AZP01-CLI-003
- Conditions
- Prader-Willi Syndrome, Hyperphagia
- Keywords
- Prader-Willi Syndrome, PWS
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Livoletide did not result in a statistically significant improvement in hyperphagia and food-related behaviors
- Enrolment
- 158 participants (actual)
- Lead sponsor
- Millendo Therapeutics SASIndustry (pharma, biotech, devices)
- Study start
- 25 Mar 2019 (actual)
- Primary completion
- 26 Feb 2020 (actual)
- Study completion
- 25 May 2020 (actual)
- First posted
- 2 Jan 2019 (actual)
- Results
- Posted 17 Feb 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This Phase 2b/3 double-blind, placebo-controlled study will evaluate the safety, tolerability, and effects of livoletide on food-related behaviors in patients with Prader-Willi Syndrome (PWS).
Detailed description
The protocol includes 2 consecutive parts:
- The first part is a Phase 2b dose-response study consisting of a 3-month double-blind, placebo-controlled Core Period followed by a 9-month Extension Period.
- The second part is a Phase 3 study consisting of a 6-month double-blind, placebo-controlled Core Period followed by a 6-month Extension Period. Phase 3 may be initiated following review of safety and efficacy results at the completion of the Phase 2b Core Period.
A total of approximately 50 patients per group (8 to 65 years of age) will be randomized (approximately 150 patients in total). In addition to this cohort of 150 patients, a separate cohort of patients 4 to 7 years of age will also be randomized.
Note: The 8-65 year old cohort has been fully enrolled. Enrollment into the 4-7 year age cohort remains ongoing.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Low-Dose Livoletide | Experimental | Drug: LivoletideDaily subcutaneous injection of ~ 60 mcg/kg for 3 month double-blind core period and 9 month open label extension period. |
| High-Dose Livoletide | Experimental | Drug: LivoletideDaily subcutaneous injection of ~120 mcg/kg for 3 month double-blind core period and 9 month open label extension period. |
| Placebo | Placebo comparator | Drug: PlaceboDaily subcutaneous injection of 0.9% NaCl for the 3 month double-blind core period and then low-dose or high-dose livoletide for 9 month open label extension period. |
Who may qualify
- Ages
- 4 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- Confirmed genetic diagnosis of PWS
- Evidence of increased appetite or hyperphagia
- Patient must have a single primary caregiver who should be available for certain durations of the study
- BMI ≤ 65 kg/m2
- Growth hormone treatment permitted if doses have been stable for at least 1 month prior to screening
Key exclusion criteria (4 listed)
- History of chronic liver disease
- Type 1 diabetes mellitus
- HbA1c > 10%
- Body weight <20 kg
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LivoletideAlso: AZP-531Daily subcutaneous injection | Drug | High-Dose Livoletide, Low-Dose Livoletide |
| PlaceboDaily subcutaneous injection | Drug | Placebo |
Primary outcome
Change in Hyperphagia and Food-related Behaviors (Hyperphagia Questionnaire for Clinical Trials; HQ-CT)
Time frame: Baseline to month 3
Change from baseline to the end of the 3-month Core Period for HQ-CT total score. The HQ-CT score range is 0 to 36 where the higher score represents more severe abnormal food related behaviors.
3 secondary outcomes
Percentage Change From Baseline to Month 3 in Total Body Fat Mass in Patients Eight to 65 Years of Age Defined as Overweight/Obese
Time frame: Baseline to month 3
Change From Baseline to Month 3 in Waist Circumference in Patients Eight to 65 Years of Age Defined as Overweight/Obese
Time frame: Baseline to month 3
Percentage Change From Baseline to Month 3 in Body Weight in Patients Eight to 65 Years of Age Defined as Overweight/Obese
Time frame: Baseline to month 3
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
37 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Livoletide in people with Prader-Willi Syndrome and Hyperphagia, run by Millendo Therapeutics SAS at 37 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 17 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 37 sites in United States, France, Australia, Spain, United Kingdom and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Feb 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Hyperphagia and Food-related Behaviors (Hyperphagia Questionnaire for Clinical Trials; HQ-CT) (time frame: Baseline to month 3). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Feb 2021.