Huntington DiseasePhase 2NCT03980938

Within Subject Crossover Study of Cognitive Effects of Neflamapimod in Early-Stage Huntington Disease

A Phase 2 study testing neflamapimod in people with Huntington Disease, run by EIP Pharma Inc at 1 site in United Kingdom.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

This is a double-blind, placebo-controlled 2-period 10-week treatment within-subject crossover study of neflamapimod in early-stage Huntington disease (HD). The primary objective is to determine whether neflamapimod can reverse hippocampal dysfunction in patients with early-stage HD, as assessed by the virtual… Read more about this study

Who is it for?: Ages 30 to 70 years
Conditions the study is for: Huntington Disease
What is being tested?: neflamapimod
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 15 participants
Where: 1 siteUnited Kingdom
Study dates: 8 Jul 2019to 15 Oct 2020
Phase: Phase 2
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 30 to 70 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Men and women age 30 to 70 years, inclusive.
Willing and able to provide informed consent.
Must have genetically confirmed HD and identified cognitive deficits:
Stage 1, as defined by Unified Huntington's Disease Rating Scale (UHDRS) Total Functional Capacity (TFC) score >10, and,
CANTAB Paired Associate Learning Total Adjusted Error Score of >16.
Normal or corrected eye sight and auditory abilities, sufficient to perform all aspects of the cognitive and functional assessments.
No history of learning difficulties that may interfere with the subject's ability to complete the cognitive tests.

Who cannot join

A profile of impairment that is not consistent with HD.
Diagnosis of any other ongoing central nervous system condition other than HD, including, but not limited to, vascular dementia, dementia with Lewy bodies, and Parkinson's disease.
Suicidality, defined as active suicidal thoughts within 6 months before Screening or at Baseline, defined as answering yes to items 4 or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS), or history of suicide attempt in previous 2 years, or, in the Investigator's opinion, at serious risk of suicide.
Ongoing major and active psychiatric disorder, moderate to severe depressive symptoms, and or other concurrent medical condition that, in the opinion of the Investigator, might compromise safety and/or compliance with study requirements.
Diagnosis of alcohol or drug abuse within the previous 2 years.
Poorly controlled clinically significant medical illness, such as hypertension (blood pressure >180 mmHg systolic or 100 mmHg diastolic); myocardial infarction within 6 months; uncompensated congestive heart failure or other significant cardiovascular, pulmonary, renal, liver, infectious disease, immune disorder, or metabolic/endocrine disorders or other disease that would preclude treatment with p38 mitogen activated protein (MAP) kinase inhibitor and/or assessment of drug safety and efficacy.

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Anemia with a hemoglobin ≤10 g/dL, clinically significant thyroid function abnormality, electrolyte abnormalities.
Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >1.5 × the upper limit of normal (ULN), total bilirubin >1.5 × ULN, and/or International Normalized Ratio (INR) >1.5.
Known human immunodeficiency virus; or active hepatitis B or hepatitis C virus infection; evidence of active or latent tuberculosis.
Subject participated in a study of an investigational drug less than 3 months or 5 half-lives of an investigational drug, whichever is longer, before enrollment in this study.
History of previous neurosurgery to the brain.
Female subjects who are pregnant or breast-feeding.
Male subjects with female partners of child-bearing potential who are unwilling or unable to adhere to contraception requirements specified in the protocol (see Section 5.8).
Female subjects who have not reached menopause or have not had a hysterectomy or bilateral oophorectomy/salpingo-oophorectomy and are not willing or unable to adhere to contraceptive requirements specified in the protocol (see Section 5.8).
Requires concomitant use of cytochrome P450 (CYP) 3A4 inhibitors or anti-tumor necrosis factor-alpha therapies during study participation.
Known allergy to any ingredient of the trial medication or placebo.

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

John Van Geest Centre for Brain Repair
Cambridge, CB2 0PY

Other trials in United Kingdom

About this study

Official title: A Double-Blind, Placebo-Controlled Two-Period 10-Week Treatment Within-Subject Crossover Study Of Cognitive Effects Of Neflamapimod in Early-Stage Huntington Disease (HD)

Read the detailed description

The study was designed as within-subject crossover study. However, due to the Covid19 lockdowns and restrictions on clinical research, and only one subject entered the second crossover period. As a result, the baseline and outcomes are reported by the actual treatment received in the subjects during what would have been the first treatment period, i.e. placebo or neflamapimod treatment.

Conditions: Huntington Disease
Being tested: neflamapimod, Placebo
Medical subject headings: Huntington Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

neflamapimodDrug
Also called VX-745
40 mg neflamapimod capsule
PlaceboOther
matching placebo capsule

Study groups in NCT03980938
Study group	Role	What they receive
neflamapimod first	Experimental	neflamapimod in Treatment Period 1, placebo in Treatment Period 2 neflamapimod: 40 mg neflamapimod hard gelatin capsules, taken twice daily with food. Placebo: hard gelatin capsules containing excipients only, weight- and size-matched; taken twice daily with food. Receives: Drug: neflamapimod; Other: Placebo
placebo first	Placebo comparator	placebo in Treatment Period 1, neflamapimod in Treatment Period 2 Placebo: hard gelatin capsules containing excipients only, weight- and size-matched; taken twice daily with food. neflamapimod: 40 mg neflamapimod hard gelatin capsules, taken twice daily with food. Receives: Drug: neflamapimod; Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Change in Latency During the Learning Phase of Virtual Morris Water Maze Test (vMWM)
Change from baseline of latency during the learning phase of vMWM (hidden platform training) in the neflamapimod first group compared to placebo first group
Measured: Baseline and 10 Weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

8 Jul 201915 Oct 2020

First posted10 Jun 2019
Study start8 Jul 2019
Primary completion15 Oct 2020
Study completion15 Oct 2020

Why it stopped: Due to the long delay because of COVID-19 and results from another study suggesting a higher dose may be more beneficial, EIP Pharma decided on October 15th, 2020, to end the trial prematurely.

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 Huntington DiseaseStudies 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
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 15 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03980938
Sponsor's protocol ID: EIP19-NFD-401
Status last verified: Apr 2022
First submitted: 7 Jun 2019
Last updated: 6 Apr 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

Tormahlen NM, Martorelli M, Kuhn A, Maier F, Guezguez J, Burnet M, Albrecht W, Laufer SA, Koch P. Design and Synthesis of Highly Selective Brain Penetrant p38alpha Mitogen-Activated Protein Kinase Inhibitors. J Med Chem. 2022 Jan 27;65(2):1225-1242. doi: 10.1021/acs.jmedchem.0c01773. Epub 2021 May 11.
PubMed 33974419

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Huntington Disease trials

Study at a glance

From the registry record, last updated by the sponsor on 6 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Double-Blind, Placebo-Controlled Two-Period 10-Week Treatment Within-Subject Crossover Study Of Cognitive Effects Of Neflamapimod in Early-Stage Huntington Disease (HD)
ClinicalTrials.gov ID: NCT03980938
Acronym / sponsor ID: EIP19-NFD-401
Conditions: Huntington Disease
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: Due to the long delay because of COVID-19 and results from another study suggesting a higher dose may be more beneficial, EIP Pharma decided on October 15th, 2020, to end the trial prematurely.
Enrolment: 15 participants (actual)
Lead sponsor: EIP Pharma IncIndustry (pharma, biotech, devices)
Collaborators: Voisin Consulting, Inc.
Study start: 8 Jul 2019 (actual)
Primary completion: 15 Oct 2020 (actual)
Study completion: 15 Oct 2020 (actual)
First posted: 10 Jun 2019 (actual)
Results: Posted 6 Apr 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
neflamapimod first	Experimental	Drug: neflamapimod, Other: Placeboneflamapimod in Treatment Period 1, placebo in Treatment Period 2 neflamapimod: 40 mg neflamapimod hard gelatin capsules, taken twice daily with food. Placebo: hard gelatin capsules containing excipients only, weight- and size-matched; taken twice daily with food.
placebo first	Placebo comparator	Drug: neflamapimod, Other: Placeboplacebo in Treatment Period 1, neflamapimod in Treatment Period 2 Placebo: hard gelatin capsules containing excipients only, weight- and size-matched; taken twice daily with food. neflamapimod: 40 mg neflamapimod hard gelatin capsules, taken twice daily with food.

Who may qualify

Ages: 30 to 70 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

Men and women age 30 to 70 years, inclusive.
Willing and able to provide informed consent.
Must have genetically confirmed HD and identified cognitive deficits:
Normal or corrected eye sight and auditory abilities, sufficient to perform all aspects of the cognitive and functional assessments.
No history of learning difficulties that may interfere with the subject's ability to complete the cognitive tests.

Key exclusion criteria (16 listed)

A profile of impairment that is not consistent with HD.
Diagnosis of any other ongoing central nervous system condition other than HD, including, but not limited to, vascular dementia, dementia with Lewy bodies, and Parkinson's disease.
Suicidality, defined as active suicidal thoughts within 6 months before Screening or at Baseline, defined as answering yes to items 4 or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS), or history of suicide attempt in previous 2 years, or, in the Investigator's opinion, at serious risk of suicide.
Ongoing major and active psychiatric disorder, moderate to severe depressive symptoms, and or other concurrent medical condition that, in the opinion of the Investigator, might compromise safety and/or compliance with study requirements.
Diagnosis of alcohol or drug abuse within the previous 2 years.

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
neflamapimodAlso: VX-74540 mg neflamapimod capsule	Drug	neflamapimod first, placebo first
Placebomatching placebo capsule	Other	neflamapimod first, placebo first

Primary outcome

Change in Latency During the Learning Phase of Virtual Morris Water Maze Test (vMWM)
Time frame: Baseline and 10 Weeks
Change from baseline of latency during the learning phase of vMWM (hidden platform training) in the neflamapimod first group compared to placebo first group

Results and safety

Results posted to the registry on 6 Apr 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Neflamapimod First	7	6
Placebo First	8	7

Primary outcome: Change in Latency During the Learning Phase of Virtual Morris Water Maze Test (vMWM)

Time frame: Baseline and 10 Weeks. Mean (Standard Deviation). Unit: seconds

Measure	Neflamapimod First n = 6	Placebo First n = 7
Value	-6.92 (3.814)	-14.05 (12.680)

Population analysed: Participants who had analyzable results at Baseline and Week 10 of Treatment Period 1 (13 participants)

Adverse events

Time frame: Up to 37 weeks. AEs occurring from when the subject signed the ICF until up to 30 days after the last dose were collected. Any AEs occurring before the start of treatment (i.e., before the first dose of the investigational product) were recorded in the medical history.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Neflamapimod First	0 of 7 (0%)	4 of 7 (57.1%)	0
Placebo First	0 of 8 (0%)	5 of 8 (62.5%)	0

Limitations and caveats (from the sponsor): Due COVID-19 pandemic all clinical research in the UK was halted in March 2020. Sponsor ultimately elected to terminate the study on 15 October 2020. As only one subject completed both periods of the crossover, the only efficacy analyses compared outcomes in subjects receiving neflamapimod (N=7) during Treatment period 1 to those receiving placebo during that period (N=8); i.e., an inter-subject group comparison, rather than the within-subject comparison for which the study was powered.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 6 Apr 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 33974419Tormahlen NM, Martorelli M, Kuhn A, Maier F, Guezguez J, Burnet M, Albrecht W, Laufer SA, Koch P. Design and Synthesis of Highly Selective Brain Penetrant p38alpha Mitogen-Activated Protein Kinase Inhibitors. J Med Chem. 2022 Jan 27;65(2):1225-1242. doi: 10.1021/acs.jmedchem.0c01773. Epub 2021 May 11.
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.

John Alam, MD study director

EIP Pharma

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 neflamapimod in people with Huntington Disease, run by EIP Pharma Inc 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 7 inclusion and 16 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 6 Apr 2022. 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?

Yes. Results are posted in the registry (first posted 6 Apr 2022). 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 Latency During the Learning Phase of Virtual Morris Water Maze Test (vMWM) (time frame: Baseline and 10 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 NCT03980938, 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 6 Apr 2022.