Fragile X SyndromePhase 2/3NCT01433354
Long-term, Safety and Tolerability Study of AFQ056 in Adolescent Patients With Fragile X Syndrome (Open-label)
A Phase 2/3 study testing AFQ056 in people with Fragile X Syndrome, run by Novartis Pharmaceuticals at 28 sites in 13 countries.
Trial summary
The purpose of this study is to generate long-term safety, tolerability and efficacy data for AFQ056 in eligible adolescent patients with FXS who have participated in the CAFQ056B2214 study, the PK study CAFQ056B2131, or another study of AFQ056 which included FXS patients below 18 years of age provided the patient is… Read more about this study
- Who is it for?
- Ages 12 to 18 years
- Conditions the study is for
- Fragile X Syndrome
- What is being tested?
- AFQ056
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 119 participants
- Where
- 28 sitesin 13 countries
- Study dates
- Nov 2011to Sep 2014
- 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 12 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Group 1 patients:
- Must have completed study CAFQ056B2214 or another study of AFQ056 which included FXS patients below 18 years of age within one week of enrollment into the open-label study.
- Has a caregiver or caregivers who spend, on average, at least 6 hours per day with the patient , who is willing to and capable of supervising treatment, providing input into efficacy and safety assessments, and accompanying the patient to study visits.
- Group 2 patients:
- Must meet one of the following conditions:
- Completed Study CAFQ056B2131
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- Completed Study CAFQ056B2214 or another study of AFQ056 which included FXS patients below 18 years of age but enrollment into the current study was delayed for more than a week.
- Discontinued prematurely from Study CAFQ056B2214 or another study of AFQ056 which included FXS patients below 18 years of age due to intolerability of the dosage in the patient's assigned treatment group.
- Has a caregiver or caregivers who spend, on average, at least 6 hours per day with the patient , who is willing to and capable of supervising treatment, providing input into efficacy and safety assessments, and accompanying the patient to study visits.
Who cannot join
- Discontinuation from Study CAFQ056B2214 or CAFQ056B2131 or another study of AFQ056 which included FXS patients below 18 years of age due to safety reasons
- Female patients who are sexually active at any time during the study
- Any advanced, severe or unstable disease
- History and/or presence of schizophrenia, bipolar disease, psychosis, confusional states and/or repeated hallucinations as per DSM-IV criteria
- History of suicidal behavior or considered a high suicidal risk
- History of severe self-injurious behavior
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- History of uncontrolled seizure disorder or resistant to therapy within the past 2 years (Patients who are clinically stable under anti-convulsant therapy for the past 2 years are not excluded)
- History of clinically significant allergies requiring hospitalization or non-inhaled corticosteroid therapy (asthma, anaphylaxis, etc.)
- History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether or not there is evidence of local recurrence or metastases
- Patients who are using (or used within 6 weeks before baseline) digoxin or warfarin
- Using (or used within 6 weeks before baseline) concomitant medications that are potent inhibitors or inducers of CYP3A4
- Using glutamatergic agents (riluzole, memantine, etc.) or lithium within 6 weeks of baseline
- Other protocol-defined inclusion/exclusion criteria may apply.
Trial locations and contacts
28 sites in 13 countries.
28 sites in 13 countries
United States7 sites
Novartis Investigative Site
Boston, Massachusetts, 02115
Novartis Investigative Site
Chicago, Illinois, 60612
Novartis Investigative Site
Decatur, Georgia, 30033
Novartis Investigative Site
Nashville, Tennessee, 37212
Novartis Investigative Site
Omaha, Nebraska, 68198-5575
Novartis Investigative Site
Sacramento, California, 95817
Novartis Investigative Site
Staten Island, New York, 10314
Germany4 sites
Novartis Investigative Site
Mainz, Germany, 55131
Novartis Investigative Site
München, 80639
Novartis Investigative Site
Tübingen, 72076
Novartis Investigative Site
Würzburg, 97070
Spain3 sites
Novartis Investigative Site
Málaga, Andalusia, 29009
Novartis Investigative Site
Sabadell, Barcelona, 08208
Novartis Investigative Site
Sant Cugat del Vallès, Catalonia, 08190
Australia2 sites
Novartis Investigative Site
Parkville, Victoria, 3052
Novartis Investigative Site
Westmead, New South Wales, 2145
Belgium2 sites
Novartis Investigative Site
Brussels, 1200
Novartis Investigative Site
Leuven, 3000
Italy2 sites
Novartis Investigative Site
Genova, GE, 16147
Novartis Investigative Site
Padova, 35128
Switzerland2 sites
Novartis Investigative Site
Lausanne
Novartis Investigative Site
Zurich, 8091
About this study
Official title: An Open-label Study to Evaluate the Long-term Safety and Tolerability of AFQ056 in Adolescent Patients With Fragile X Syndrome
The purpose of this study is to generate long-term safety, tolerability and efficacy data for AFQ056 in eligible adolescent patients with FXS who have participated in the CAFQ056B2214 study, the PK study CAFQ056B2131, or another study of AFQ056 which included FXS patients below 18 years of age provided the patient is at least 12 years of age at the time of entry into the current study.
- Conditions
- Fragile X Syndrome
- Being tested
- AFQ056
- Keywords
- Fragile X Syndrome, Martin-Bell Syndrome, Genetic Diseases, X-Linked, Escalante's syndrome
- Medical subject headings
- Fragile X Syndrome, Genetic Diseases, Inborn
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AFQ056Drug
The investigational drug, AFQ056, will be provided as hard gelatin capsules. Two different oral dosage strengths,25mg and 100 mg, identical in appearance, will be used.
| Study group | Role | What they receive |
|---|---|---|
| AFQ056 Treatment | Experimental | All patients will initiate treatment with AFQ056 at a starting dose of 25 mg b.i.d. The dose will be titrated from 25 mg b.i.d to 50 mg b.i.d., 75 mg b.i.d. and 100 mg b.i.d. at weekly intervals. Dose adjustments (up- and down-titrations) will be permitted as needed to manage any tolerability issues and to ensure that patients reach their highest tolerated dose, not to exceed 100 mg b.i.d. Receives: Drug: AFQ056 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Adverse events were summarized for the open-label treatment period, where the open-label treatment period is defined based on how AEs were collected and reported according to the manner in which participants entered the current study and which treatment (AFQ056 or placebo) they were receiving in the previous study.
AEs which were continuing from the core study or that started after the end of core study but prior to first dose of open-label study medication in the extension study for Category 1 participants are shown under 'Prior to Ext. first dose'.
AEs which started during the open-label treatment period are presented based on the last AFQ056 dose taken on or before the onset date of the AE (25 mg bid; 50 mg bid; 75 mg bid; or 100 mg bid). No efficacy data presented as study was terminated.
Measured: Prior to first dose in extension study, Baseline (start of study treatment in extension study) to End of trial
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Sep 2011 (estimated)
- Study startNov 2011
- Primary completionSep 2014
- Study completionSep 2014
Why it stopped: The study treatment failed to demonstrate efficacy in target population in two other clinical studies (CAFQ056B2214 and CAFQ056A2212).
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Fragile X SyndromeStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 119 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01433354
- Sponsor's protocol ID
- CAFQ056B2278
- Other IDs
- 2011-002379-40
- Status last verified
- Feb 2016
- First submitted
- 31 Aug 2011
- Last updated
- 24 Mar 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Bailey DB Jr, Berry-Kravis E, Wheeler A, Raspa M, Merrien F, Ricart J, Koumaras B, Rosenkranz G, Tomlinson M, von Raison F, Apostol G. Mavoglurant in adolescents with fragile X syndrome: analysis of Clinical Global Impression-Improvement source data from a double-blind therapeutic study followed by an open-label, long-term extension study. J Neurodev Disord. 2016;8:1. doi: 10.1186/s11689-015-9134-5. Epub 2015 Dec 15.
PubMed 26855682
Study at a glance
From the registry record, last updated by the sponsor on 24 Mar 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label Study to Evaluate the Long-term Safety and Tolerability of AFQ056 in Adolescent Patients With Fragile X Syndrome
- ClinicalTrials.gov ID
- NCT01433354
- Acronym / sponsor ID
- CAFQ056B2278
- Conditions
- Fragile X Syndrome
- Keywords
- Fragile X Syndrome, Martin-Bell Syndrome, Genetic Diseases, X-Linked, Escalante's syndrome
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study treatment failed to demonstrate efficacy in target population in two other clinical studies (CAFQ056B2214 and CAFQ056A2212).
- Enrolment
- 119 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Nov 2011
- Primary completion
- Sep 2014 (actual)
- Study completion
- Sep 2014 (actual)
- First posted
- 13 Sep 2011 (estimated)
- Results
- Posted 12 Oct 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to generate long-term safety, tolerability and efficacy data for AFQ056 in eligible adolescent patients with FXS who have participated in the CAFQ056B2214 study, the PK study CAFQ056B2131, or another study of AFQ056 which included FXS patients below 18 years of age provided the patient is at least 12 years of age at the time of entry into the current study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| AFQ056 Treatment | Experimental | Drug: AFQ056All patients will initiate treatment with AFQ056 at a starting dose of 25 mg b.i.d. The dose will be titrated from 25 mg b.i.d to 50 mg b.i.d., 75 mg b.i.d. and 100 mg b.i.d. at weekly intervals. Dose adjustments (up- and down-titrations) will be permitted as needed to manage any tolerability issues and to ensure that patients reach their highest tolerated dose, not to exceed 100 mg b.i.d. |
Who may qualify
- Ages
- 12 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (9 listed)
- Group 1 patients:
- Must have completed study CAFQ056B2214 or another study of AFQ056 which included FXS patients below 18 years of age within one week of enrollment into the open-label study.
- Has a caregiver or caregivers who spend, on average, at least 6 hours per day with the patient , who is willing to and capable of supervising treatment, providing input into efficacy and safety assessments, and accompanying the patient to study visits.
- Group 2 patients:
- Must meet one of the following conditions:
Key exclusion criteria (13 listed)
- Discontinuation from Study CAFQ056B2214 or CAFQ056B2131 or another study of AFQ056 which included FXS patients below 18 years of age due to safety reasons
- Female patients who are sexually active at any time during the study
- Any advanced, severe or unstable disease
- History and/or presence of schizophrenia, bipolar disease, psychosis, confusional states and/or repeated hallucinations as per DSM-IV criteria
- History of suicidal behavior or considered a high suicidal risk
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 |
|---|---|---|
| AFQ056The investigational drug, AFQ056, will be provided as hard gelatin capsules. Two different oral dosage strengths,25mg and 100 mg, identical in appearance, will be used. | Drug | AFQ056 Treatment |
Primary outcome
Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Prior to first dose in extension study, Baseline (start of study treatment in extension study) to End of trial
Adverse events were summarized for the open-label treatment period, where the open-label treatment period is defined based on how AEs were collected and reported according to the manner in which participants entered the current study and which treatment (AFQ056 or placebo) they were receiving in the previous study. AEs which were continuing from the core study or that started after the end of core study but prior to first dose of open-label study medication in the extension study for Category 1 participants are shown under 'Prior to Ext. first dose'. AEs which started during the open-label treatment period are presented based on the last AFQ056 dose taken on or before the onset date of the AE (25 mg bid; 50 mg bid; 75 mg bid; or 100 mg bid). No efficacy data presented as study was terminated.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Mar 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 26855682Bailey DB Jr, Berry-Kravis E, Wheeler A, Raspa M, Merrien F, Ricart J, Koumaras B, Rosenkranz G, Tomlinson M, von Raison F, Apostol G. Mavoglurant in adolescents with fragile X syndrome: analysis of Clinical Global Impression-Improvement source data from a double-blind therapeutic study followed by an open-label, long-term extension study. J Neurodev Disord. 2016;8:1. doi: 10.1186/s11689-015-9134-5. Epub 2015 Dec 15.
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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.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
28 sites in 13 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing AFQ056 in people with Fragile X Syndrome, run by Novartis Pharmaceuticals at 28 sites in 13 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 9 inclusion and 13 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 24 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 28 sites in United States, Germany, Spain, Australia, Belgium and 8 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. 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 12 Oct 2015). 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?
Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) (time frame: Prior to first dose in extension study, Baseline (start of study treatment in extension study) to End of trial). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01433354, which also lists 1 linked publication.
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 24 Mar 2016.