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AzTrials

Huntington's DiseasePhase 1/2NCT02519036

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ISIS 443139 in Participants With Early Manifest Huntington's Disease

A Phase 1/2 study testing ISIS 443139 10 mg, ISIS 443139 30 mg and ISIS 443139 60 mg in people with Huntington's Disease, run by Ionis Pharmaceuticals, Inc. at 9 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This study tested the safety, tolerability, pharmacokinetics and pharmacodynamics of multiple ascending doses of ISIS 443139 administered intrathecally to adult participants with early manifest Huntington's Disease. Read more about this study

Who is it for?
Ages 25 to 65 years
Conditions the study is for
Huntington's Disease
What is being tested?
ISIS 443139 10 mg, ISIS 443139 30 mg and ISIS 443139 60 mg
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
46 participants
Where
9 sitesin 3 countries
Study dates
6 Aug 2015to 8 Nov 2017
Phase
Phase 1/2
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 25 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Diagnosed with early manifest Huntington's disease
  • Male or female, aged 25 to 65 years, inclusive, at the time of informed consent
  • Able and willing to meet all study requirements, including travel to Study Center and participation in all procedures and measurements at study visits
  • Have a trial partner who is reliable, competent and at least 18 years of age, is willing to accompany the participant to select trial visits and to be available to the Study Center by phone if needed
  • Able to tolerate MRI scans, blood draws and lumbar punctures
  • Reside within 4 hours travel of the Study Center

Who cannot join

  • Clinically significant medical condition, such as severe chorea, active suicidal ideation or any other conditions which would make the participant unsuitable for inclusion or could interfere with the participant participating in or completing the study
  • Recent treatment with another investigational drug, biological agent, or device
  • Prior treatment with an antisense oligonucleotide [including small interfering ribonucleic acid (siRNA)]
  • Any history of gene therapy or cell transplantation or any other experimental brain surgery
  • Presence of an implanted shunt for the drainage of cerebrospinal fluid (CSF) or an implanted central nervous system (CNS) catheter
  • History of post-lumbar-puncture headache of moderate or severe intensity and/or blood patch
  • Malignancy within 5 years of Screening, except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has been successfully treated
  • Hospitalization for any major medical or surgical procedure involving general anesthesia within 12 weeks of Screening or planned during the study

Trial locations and contacts

9 sites in 3 countries.

9 sites in 3 countries

United Kingdom5 sites

  • University Hospitals Birmingham

    Birmingham, B15 2TH

  • Cambridge University Hospital

    Cambridge, CB2 0PY

  • University Hospital of Wales

    Cardiff, CF14 4XN

  • University College London

    London, WC1N 3BG

  • University of Manchester, St. Mary's Hospital

    Manchester, M13 9WL

Other trials in United Kingdom

Germany3 sites

  • Charite University Berlin

    Berlin, 10117

  • Ruhr-University of Bochum

    Bochum, 44791

  • Ulm University Hospital

    Ulm, 89081

Other trials in Germany

Canada1 site

  • University of British Columbia

    Vancouver, British Columbia, V6T 2B5

Other trials in Canada

About this study

Official title: A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Ascending Doses of Intrathecally Administered ISIS 443139 in Patients With Early Manifest Huntington's Disease

This study tested the safety, tolerability, pharmacokinetics and pharmacodynamics of multiple ascending doses of ISIS 443139 administered intrathecally to adult participants with early manifest Huntington's Disease.

Being tested
ISIS 443139 10 mg, ISIS 443139 30 mg, ISIS 443139 60 mg, ISIS 443139 90 mg, ISIS 443139 120 mg
Keywords
Huntington's Disease, HTTRx, Early Manifest Huntington's Disease
Medical subject headings
Huntington Disease

What participants receive

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

  • ISIS 443139 10 mgDrug

    Also called IONIS HTTRx

    ISIS 443139, 10 mg, was administered by intrathecal injection, on Study Days 1, 29, 57, and 85.

  • ISIS 443139 30 mgDrug

    Also called IONIS HTTRx

    ISIS 443139, 30 mg, was administered by intrathecal injection, on Study Days 1, 29, 57, and 85.

  • ISIS 443139 60 mgDrug

    Also called IONIS HTTRx

    ISIS 443139, 60 mg, was administered by intrathecal injection, on Study Days 1, 29, 57, and 85.

  • ISIS 443139 90 mgDrug

    Also called IONIS HTTRx

    ISIS 443139, 90 mg, was administered by intrathecal injection, on Study Days 1, 29, 57, and 85.

  • ISIS 443139 120 mgDrug

    Also called IONIS HTTRx

    ISIS 443139, 120 mg, was administered by intrathecal injection, on Study Days 1, 29, 57, and 85.

  • PlaceboOther

    Placebo was administered by intrathecal injection, on Study Days 1, 29, 57, and 85.

Study groups in NCT02519036
Study groupRoleWhat they receive
ISIS 443139 10 mgExperimentalParticipants received ISIS 443139, 10 milligrams (mg), by intrathecal injection, on Study Days 1, 29, 57, and 85.
Receives: Drug: ISIS 443139 10 mg
ISIS 443139 30 mgExperimentalParticipants received ISIS 443139, 30 mg, by intrathecal injection, on Study Days 1, 29, 57, and 85.
Receives: Drug: ISIS 443139 30 mg
ISIS 443139 60 mgExperimentalParticipants received ISIS 443139, 60 mg, by intrathecal injection, on Study Days 1, 29, 57, and 85.
Receives: Drug: ISIS 443139 60 mg
ISIS 443139 90 mgExperimentalParticipants received ISIS 443139, 90 mg, by intrathecal injection, on Study Days 1, 29, 57, and 85.
Receives: Drug: ISIS 443139 90 mg
ISIS 443139 120 mgExperimentalParticipants received ISIS 443139, 120 mg, by intrathecal injection, on Study Days 1, 29, 57, and 85.
Receives: Drug: ISIS 443139 120 mg
PlaceboPlacebo comparatorParticipants received placebo, by intrathecal injection, on Study Days 1, 29, 57, and 85.
Receives: Other: Placebo

What is being measured

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

  1. Number of Participants With Treatment-related Adverse Events (TEAEs)

    An adverse event (AE) was any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the study or use of investigational drug product, whether or not the AE was considered related to the investigational drug product. An AE was to be regarded as a TEAE if it was present prior to receiving the first dose of Study Drug and subsequently worsened or was not present prior to receiving the first dose of Study Drug but subsequently appeared.

    Measured: Up to approximately 28 weeks

Secondary outcomes (1)

  1. Observed Cerebrospinal Fluid (CSF) Concentration for ISIS 443139

    Measured: Days 1, 29, 57, 85, and 113 or 141

Timeline

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

  1. First posted10 Aug 2015 (estimated)
  2. Study start6 Aug 2015
  3. Primary completion8 Nov 2017
  4. Study completion8 Nov 2017

Resources

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 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
46 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02519036
Sponsor's protocol ID
ISIS 443139-CS1
Other IDs
2015-000381-66, 2015
Status last verified
May 2019
First submitted
1 Aug 2015
Last updated
31 May 2019
Data monitoring committee
Yes
FDA-regulated drug
Yes

Publications

  • Rodrigues FB, Ferreira JJ, Wild EJ. Huntington's Disease Clinical Trials Corner: June 2019. J Huntingtons Dis. 2019;8(3):363-371. doi: 10.3233/JHD-199003.

    PubMed 31381524

  • Tabrizi SJ, Leavitt BR, Landwehrmeyer GB, Wild EJ, Saft C, Barker RA, Blair NF, Craufurd D, Priller J, Rickards H, Rosser A, Kordasiewicz HB, Czech C, Swayze EE, Norris DA, Baumann T, Gerlach I, Schobel SA, Paz E, Smith AV, Bennett CF, Lane RM; Phase 1-2a IONIS-HTTRx Study Site Teams. Targeting Huntingtin Expression in Patients with Huntington's Disease. N Engl J Med. 2019 Jun 13;380(24):2307-2316. doi: 10.1056/NEJMoa1900907. Epub 2019 May 6.

    PubMed 31059641

  • Rodrigues FB, Wild EJ. Huntington's Disease Clinical Trials Corner: February 2018. J Huntingtons Dis. 2018;7(1):89-98. doi: 10.3233/JHD-189001.

    PubMed 29480210

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing ISIS 443139 10 mg, ISIS 443139 30 mg and ISIS 443139 60 mg in people with Huntington's Disease, run by Ionis Pharmaceuticals, Inc. at 9 sites in 3 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 6 inclusion and 8 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 31 May 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in United Kingdom, Germany, Canada. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 31 May 2019). 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?

Number of Participants With Treatment-related Adverse Events (TEAEs) (time frame: Up to approximately 28 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 NCT02519036, 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 31 May 2019.

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