Trigeminal NeuralgiaPhase 2NCT01540630
A Phase IIa Withdrawal Study of CNV1014802 in Patients With Trigeminal Neuralgia
A Phase 2 study testing CNV1014802 in people with Trigeminal Neuralgia, run by Biogen at 1 site in United Kingdom.
Trial summary
This is a double-blind, randomized withdrawal study comparing CNV1014802 with placebo in patients with trigeminal neuralgia who have successfully responded to CNV1014802 in an initial open-label phase. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Trigeminal Neuralgia
- What is being tested?
- CNV1014802
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 67 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 31 Mar 2012to 30 Jun 2014
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female aged between 18 and 70 years, with a diagnosis of trigeminal neuralgia; IHS criteria to be used.
- Female patients must be of non-child bearing potential or agree to use an approved form of contraception
- Male patients must agree to use an approved form of contraception
- Body weight > 50 kg for men and > 45 kg for women.
- BMI ≤ 34.9
- Capable of giving written informed consent. Informed consent must be obtained prior to the commencement of any study related procedures.
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- QTcB either/or QTcF < 450 msec in two of three ECGs conducted at screening
- AST and ALT < 2xULN; alkaline phosphatase and bilirubin < 1.5xULN.
- Approved concomitant medications must have been stable for at least 3 weeks prior to day 0.
Who cannot join
- Patients who are known non-responders to sodium channel blockers at therapeutic doses.
- Patients with causes for their facial pain other than that specified in Inclusion Criterion
- A positive pre-study drug screen.
- A positive history of HIV.
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
- History of any liver disease within the last 6 months, with the exception of known Gilbert's disease.
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- History of excessive regular alcohol consumption within 6 months of the study.
- Patients with a history or risk of seizures or a history of epilepsy, head injury or related neurological disorders
- Patients with a history of uncontrolled or poorly controlled hypertension, with systolic BP frequently exceeding 160mmHg and/or diastolic BP frequently exceeding 100mmHg, or patients who have BP greater than or equal to 160mmHg systolic and/or greater than or equal to 100mmHg diastolic at screening after repeated measurements
- History or presence of significant cardiovascular, gastro-intestinal, or renal disease or other condition known to interfere with the absorption, distribution, metabolism, or excretion of drugs.
- Patients with conditions known to affect cardiac conduction or a personal or familial history of Brugada syndrome
- Pregnant females or lactating females.
- History or presence of any clinically significant abnormality in vital signs/ECG/laboratory tests or have any medical or psychiatric condition, which, in the opinion of the Investigator may interfere with the study procedures or compromise patient safety.
- History of suicidal ideation and/or suicide attempts or clinical evidence of recent major depression.
- Patients who are unable to maintain approved medications for their trigeminal neuralgia at a stable dose during the study.
- Unable to refrain from excessive use of sedatives.
- Unable to comply with the prohibited concomitant medication restrictions as detailed in the protocol. This includes but is not limited to sodium channel blockers or drugs that adversely interact with a monoamine oxidase-B inhibitor: MAOI's, antidepressants, opioids and sympathomimetic agents.
- History of hypersensitivity to CNV1014802.
- The patient has participated in a clinical trial and has received an investigational product within 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer) prior to the start of this study.
- Exposure to more than four new chemical entities (medications for which no marketing authorization has been obtained) within 12 months prior to the first dosing day.
- Where participation in the study would result in total donation of blood or blood products in excess of 500mL within a 56 day period.
- Patient is mentally or legally incapacitated.
- Unwillingness or inability to follow the procedures outlined in the protocol.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase IIa Placebo-Controlled, Double-Blind Randomized Withdrawal Study to Evaluate the Safety and Efficacy of CNV1014802 in Patients With Trigeminal Neuralgia
This is a double-blind, randomized withdrawal study comparing CNV1014802 with placebo in patients with trigeminal neuralgia who have successfully responded to CNV1014802 in an initial open-label phase.
Patients will participate in an initial open-label treatment period of 21 days of CNV1014802 150mg three times a day (tid). Responders will be randomized to 28 days of CNV1014802 150mg tid or placebo.
Following an interim analysis after 10 evaluable patients have completed the open-label phase, the dose regimen may be increased to 350mg twice a day (bid) for the remainder of the trial if the responder rate is less than 60%.
Read the detailed description
In order to be randomised and enter the double-blind placebo controlled phase of the study, patients must satisfy at least one of the following criteria:
- 30% or more decrease in number of paroxysms (either spontaneous, evoked, or both)
- 30% reduction in the severity of pain experienced during the paroxysm (either spontaneous, evoked or both)
- A Patient Global Improvement of Change rating of much improved/very much improved The response will be compared with the baseline recordings of pain made in the 7 day run-in period. If a patient meets one of these criteria they are termed a responder, and will be eligible to be randomized into the double-blind treatment phase.
During the double-blind randomised phase, patients will be evaluated to determine if they meet the failure criteria at each clinic visit which will occur every 7 days in the double-blind treatment period. The number of failures on CNV1014802 versus number of failures on placebo during the double-blind treatment period will be the primary outcome of the study.
Patients will be classified as a treatment failure if they meet one of the following criteria:
- 50% increase in the frequency of paroxysms compared to the final 7 days of the open-label period
- 50% increase in the severity of pain experienced in the paroxysms compared to the final 7 days of the open-label period
- A Patient Global Improvement of Change rating of much worse/very much worse
- The patient discontinues the study due to 'Lack of Efficacy'
- The patient discontinues due to an adverse reaction or poor tolerability considered to be related to study medication
This study was previously posted by Convergence Pharmaceuticals, Ltd., which has been acquired by Biogen.
- Conditions
- Trigeminal Neuralgia
- Being tested
- CNV1014802, Placebo
- Medical subject headings
- Trigeminal Neuralgia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CNV1014802Drug
CNV1014802 150mg tid for 28 days. Dose may be increased to 350mg bid following interim evaluation of efficacy.
PlaceboDrug
Double-blind placebo comparator for 28 days.
| Study group | Role | What they receive |
|---|---|---|
| CNV1014802 | Experimental | Not described Receives: Drug: CNV1014802 |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The number of failures on CNV1014802 vs. number of failures on placebo during the double-blind treatment period will be the primary outcome of the study.
Patients will be classified as a treatment failure if they meet one of the following criteria:
- 50% increase in the frequency of paroxysms compared to the final 7 days of the open-label period
- 50% increase in the severity of pain experienced in the paroxysms compared to the final 7 days of the open-label period
- A Patient Global Improvement of Change rating of much worse/very much worse
- The patient discontinues the study due to 'Lack of Efficacy'. v. The patient discontinues due to an adverse reaction or poor tolerability considered to be related to study medication
Measured: 4 weeks
Secondary outcomes (1)
Secondary pain endpoints
- Number and severity of paroxysms of pain in the 21 day open-label period, both evoked and spontaneous
- Average 24 hour pain intensity numerical rating scale (PI-NRS)
- Patient and Physician Clinical Global Impression of Change
- Brief Pain Inventory - Facial
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Feb 2012 (estimated)
- Study start31 Mar 2012
- Primary completion31 Mar 2014
- Study completion30 Jun 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Trigeminal NeuralgiaStudies of the same condition, open and under way.
- More trials run by BiogenThe 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 67 participants (actual)
Sponsor and investigators
- Lead sponsor
- Biogen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Biogen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01540630
- Sponsor's protocol ID
- CNV1014802/202
- Status last verified
- Jan 2019
- First submitted
- 23 Feb 2012
- Last updated
- 10 Jan 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Zakrzewska JM, Palmer J, Ettlin DA, Obermann M, Giblin GM, Morisset V, Tate S, Gunn K. Novel design for a phase IIa placebo-controlled, double-blind randomized withdrawal study to evaluate the safety and efficacy of CNV1014802 in patients with trigeminal neuralgia. Trials. 2013 Nov 23;14:402. doi: 10.1186/1745-6215-14-402.
PubMed 24267010Zakrzewska JM, Palmer J, Bendtsen L, Di Stefano G, Ettlin DA, Maarbjerg S, Obermann M, Morisset V, Steiner D, Tate S, Cruccu G. Challenges recruiting to a proof-of-concept pharmaceutical trial for a rare disease: the trigeminal neuralgia experience. Trials. 2018 Dec 27;19(1):704. doi: 10.1186/s13063-018-3045-1.
PubMed 30587219Zakrzewska JM, Palmer J, Morisset V, Giblin GM, Obermann M, Ettlin DA, Cruccu G, Bendtsen L, Estacion M, Derjean D, Waxman SG, Layton G, Gunn K, Tate S; study investigators. Safety and efficacy of a Nav1.7 selective sodium channel blocker in patients with trigeminal neuralgia: a double-blind, placebo-controlled, randomised withdrawal phase 2a trial. Lancet Neurol. 2017 Apr;16(4):291-300. doi: 10.1016/S1474-4422(17)30005-4. Epub 2017 Feb 17.
PubMed 28216232
Study at a glance
From the registry record, last updated by the sponsor on 10 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IIa Placebo-Controlled, Double-Blind Randomized Withdrawal Study to Evaluate the Safety and Efficacy of CNV1014802 in Patients With Trigeminal Neuralgia
- ClinicalTrials.gov ID
- NCT01540630
- Acronym / sponsor ID
- CNV1014802/202
- Conditions
- Trigeminal Neuralgia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 67 participants (actual)
- Lead sponsor
- BiogenIndustry (pharma, biotech, devices)
- Study start
- 31 Mar 2012 (actual)
- Primary completion
- 31 Mar 2014 (actual)
- Study completion
- 30 Jun 2014 (actual)
- First posted
- 29 Feb 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a double-blind, randomized withdrawal study comparing CNV1014802 with placebo in patients with trigeminal neuralgia who have successfully responded to CNV1014802 in an initial open-label phase.
Patients will participate in an initial open-label treatment period of 21 days of CNV1014802 150mg three times a day (tid). Responders will be randomized to 28 days of CNV1014802 150mg tid or placebo.
Following an interim analysis after 10 evaluable patients have completed the open-label phase, the dose regimen may be increased to 350mg twice a day (bid) for the remainder of the trial if the responder rate is less than 60%.
Detailed description
In order to be randomised and enter the double-blind placebo controlled phase of the study, patients must satisfy at least one of the following criteria:
- 30% or more decrease in number of paroxysms (either spontaneous, evoked, or both)
- 30% reduction in the severity of pain experienced during the paroxysm (either spontaneous, evoked or both)
- A Patient Global Improvement of Change rating of much improved/very much improved The response will be compared with the baseline recordings of pain made in the 7 day run-in period. If a patient meets one of these criteria they are termed a responder, and will be eligible to be randomized into the double-blind treatment phase.
During the double-blind randomised phase, patients will be evaluated to determine if they meet the failure criteria at each clinic visit which will occur every 7 days in the double-blind treatment period. The number of failures on CNV1014802 versus number of failures on placebo during the double-blind treatment period will be the primary outcome of the study.
Patients will be classified as a treatment failure if they meet one of the following criteria:
- 50% increase in the frequency of paroxysms compared to the final 7 days of the open-label period
- 50% increase in the severity of pain experienced in the paroxysms compared to the final 7 days of the open-label period
- A Patient Global Improvement of Change rating of much worse/very much worse
- The patient discontinues the study due to 'Lack of Efficacy'
- The patient discontinues due to an adverse reaction or poor tolerability considered to be related to study medication
This study was previously posted by Convergence Pharmaceuticals, Ltd., which has been acquired by Biogen.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CNV1014802 | Experimental | Drug: CNV1014802 |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Male or female aged between 18 and 70 years, with a diagnosis of trigeminal neuralgia; IHS criteria to be used.
- Female patients must be of non-child bearing potential or agree to use an approved form of contraception
- Male patients must agree to use an approved form of contraception
- Body weight > 50 kg for men and > 45 kg for women.
- BMI ≤ 34.9
Key exclusion criteria (23 listed)
- Patients who are known non-responders to sodium channel blockers at therapeutic doses.
- Patients with causes for their facial pain other than that specified in Inclusion Criterion
- A positive pre-study drug screen.
- A positive history of HIV.
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
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 |
|---|---|---|
| CNV1014802CNV1014802 150mg tid for 28 days. Dose may be increased to 350mg bid following interim evaluation of efficacy. | Drug | CNV1014802 |
| PlaceboDouble-blind placebo comparator for 28 days. | Drug | Placebo |
Primary outcome
The number of failures on CNV1014802 vs. number of failures on placebo during the double-blind treatment period will be the primary outcome of the study.
Time frame: 4 weeks
Patients will be classified as a treatment failure if they meet one of the following criteria: * 50% increase in the frequency of paroxysms compared to the final 7 days of the open-label period * 50% increase in the severity of pain experienced in the paroxysms compared to the final 7 days of the open-label period * A Patient Global Improvement of Change rating of much worse/very much worse * The patient discontinues the study due to 'Lack of Efficacy'. v. The patient discontinues due to an adverse reaction or poor tolerability considered to be related to study medication
1 secondary outcome
Secondary pain endpoints
Time frame: 4 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jan 2019.
- Background: PubMed 24267010Zakrzewska JM, Palmer J, Ettlin DA, Obermann M, Giblin GM, Morisset V, Tate S, Gunn K. Novel design for a phase IIa placebo-controlled, double-blind randomized withdrawal study to evaluate the safety and efficacy of CNV1014802 in patients with trigeminal neuralgia. Trials. 2013 Nov 23;14:402. doi: 10.1186/1745-6215-14-402.
- Derived from this study: PubMed 30587219Zakrzewska JM, Palmer J, Bendtsen L, Di Stefano G, Ettlin DA, Maarbjerg S, Obermann M, Morisset V, Steiner D, Tate S, Cruccu G. Challenges recruiting to a proof-of-concept pharmaceutical trial for a rare disease: the trigeminal neuralgia experience. Trials. 2018 Dec 27;19(1):704. doi: 10.1186/s13063-018-3045-1.
- Derived from this study: PubMed 28216232Zakrzewska JM, Palmer J, Morisset V, Giblin GM, Obermann M, Ettlin DA, Cruccu G, Bendtsen L, Estacion M, Derjean D, Waxman SG, Layton G, Gunn K, Tate S; study investigators. Safety and efficacy of a Nav1.7 selective sodium channel blocker in patients with trigeminal neuralgia: a double-blind, placebo-controlled, randomised withdrawal phase 2a trial. Lancet Neurol. 2017 Apr;16(4):291-300. doi: 10.1016/S1474-4422(17)30005-4. Epub 2017 Feb 17.
- EudraCT Tabulated ResultLink provided by the sponsor.
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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.
Medical Director study director
Biogen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing CNV1014802 in people with Trigeminal Neuralgia, run by Biogen at 1 site in United Kingdom.
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 23 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: finished, as of the sponsor's last update on 10 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
The number of failures on CNV1014802 vs. number of failures on placebo during the double-blind treatment period will be the primary outcome of the study. (time frame: 4 weeks). 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 NCT01540630, which also lists 3 linked publications.
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 10 Jan 2019.