NCT02519036 is a Phase 1, PHASE2 clinical trial of ISIS 443139 10 mg in Huntington's Disease, sponsored by Ionis Pharmaceuticals, Inc..

Who is sponsoring NCT02519036?

NCT02519036 is sponsored by Ionis Pharmaceuticals, Inc..

What drugs are being tested in NCT02519036?

Interventions in NCT02519036: ISIS 443139 10 mg, ISIS 443139 30 mg, ISIS 443139 60 mg, ISIS 443139 90 mg, ISIS 443139 120 mg, Placebo.

What condition does NCT02519036 study?

NCT02519036 studies Huntington's Disease.

Is NCT02519036 still recruiting?

NCT02519036 is currently completed. Last updated 31 May 2019.

Are results published for NCT02519036?

Yes — primary outcome results have been posted to ClinicalTrials.gov. See the outcomes section above for details.

Last reviewed 2019-05-31 · How we verify

NCT02519036

Name: Drug Landscape Pharmaceutical Database
Creator: Drug Landscape
Published: 2026-01-01
License: https://creativecommons.org/licenses/by/4.0/

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

Completed Phase 1, PHASE2 Results posted Last updated 31 May 2019

What this trial tests

Phase 1, PHASE2 trial testing ISIS 443139 10 mg in Huntington's Disease in 46 participants. Completed in 8 November 2017.

Timeline

6 August 2015

Primary endpoint
8 November 2017

8 November 2017

Quick facts

Lead sponsor	Ionis Pharmaceuticals, Inc.
Phase	Phase 1, PHASE2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	46
Start date	6 August 2015
Primary completion	8 November 2017
Estimated completion	8 November 2017
Sites	9 locations across United Kingdom, Canada, Germany

Drugs / interventions tested

ISIS 443139 10 mg — full drug profile →
ISIS 443139 30 mg — full drug profile →
ISIS 443139 60 mg — full drug profile →
ISIS 443139 90 mg — full drug profile →
ISIS 443139 120 mg — full drug profile →
Placebo

Conditions studied

Huntington's Disease — all drugs for Huntington's Disease →

Sponsor

Ionis Pharmaceuticals, Inc. — full company profile →

Who can join

Adults 25 to 65, any sex, with Huntington's Disease. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Treatment-related Adverse Events (TEAEs) Primary · Up to approximately 28 weeks

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.

Group	Value	95% CI
Placebo	12
ISIS 443139 10 mg	3
ISIS 443139 30 mg	6
ISIS 443139 60 mg	6
ISIS 443139 90 mg	9
ISIS 443139 120 mg	9

Observed Cerebrospinal Fluid (CSF) Concentration for ISIS 443139 Secondary · Days 1, 29, 57, 85, and 113 or 141

Day 1

Group	Value	95% CI
ISIS 443139 10 mg	NA	± NA
ISIS 443139 30 mg	NA	± NA
ISIS 443139 60 mg	NA	± NA
ISIS 443139 90 mg	NA	± NA
ISIS 443139 120 mg	NA	± NA

Day 29

Group	Value	95% CI
ISIS 443139 10 mg	NA	± NA
ISIS 443139 30 mg	NA	± NA
ISIS 443139 60 mg	1.77	± 1.61
ISIS 443139 90 mg	1.55	± 1.06
ISIS 443139 120 mg	2.06	± 1.01

Day 57

Group	Value	95% CI
ISIS 443139 10 mg	NA	± NA
ISIS 443139 30 mg	1.69	± 0.530
ISIS 443139 60 mg	2.77	± 2.04
ISIS 443139 90 mg	2.36	± 1.34
ISIS 443139 120 mg	2.40	± 1.24

Day 85

Group	Value	95% CI
ISIS 443139 10 mg	NA	± NA
ISIS 443139 30 mg	1.96	± 1.22
ISIS 443139 60 mg	2.88	± 2.54
ISIS 443139 90 mg	2.05	± 1.25
ISIS 443139 120 mg	2.53	± 0.628

Day 113

Group	Value	95% CI
ISIS 443139 10 mg	NA	± NA
ISIS 443139 30 mg	1.63	± 0.250
ISIS 443139 60 mg	1.84	± 1.71
ISIS 443139 90 mg	2.28	± 0.438
ISIS 443139 120 mg	2.70	± 1.20

Day 141

Group	Value	95% CI
ISIS 443139 30 mg	NA	± NA
ISIS 443139 60 mg	NA	± NA
ISIS 443139 90 mg	NA	± NA
ISIS 443139 120 mg	NA	± NA

Maximum Plasma Concentration (Cmax) for ISIS 443139 Secondary · Days 1 and 85

Day 1

Group	Value	95% CI
ISIS 443139 10 mg	74.0	± 24.3
ISIS 443139 30 mg	203	± 81.9
ISIS 443139 60 mg	500	± 39.0
ISIS 443139 90 mg	600	± 94.9
ISIS 443139 120 mg	717	± 69.2

Day 85

Group	Value	95% CI
ISIS 443139 10 mg	124	± 73.6
ISIS 443139 30 mg	179	± 55.1
ISIS 443139 60 mg	396	± 77.2
ISIS 443139 90 mg	439	± 86.0
ISIS 443139 120 mg	731	± 90.6

Time to Maximum Plasma Concentration (Tmax) for ISIS 443139 Secondary · Days 1 and 85

Day 1

Group	Value	95% CI
ISIS 443139 10 mg	3.03	2.05 – 5.95
ISIS 443139 30 mg	3.03	2.00 – 4.00
ISIS 443139 60 mg	1.99	0.533 – 3.08
ISIS 443139 90 mg	3.05	2.00 – 8.02
ISIS 443139 120 mg	4.00	2.00 – 23.8

Day 85

Group	Value	95% CI
ISIS 443139 10 mg	2.02	0.717 – 3.02
ISIS 443139 30 mg	2.03	0.550 – 3.07
ISIS 443139 60 mg	2.02	1.00 – 4.02
ISIS 443139 90 mg	3.02	0.600 – 5.02
ISIS 443139 120 mg	4.03	2.00 – 23.9

Change From Baseline in CSF Mutant Huntingtin (fM) Protein Concentration Secondary · Baseline to Final Assessment (Day 85 or 113)

Baseline was defined as the last non-missing measure prior to the first dose.

Baseline

Group	Value	95% CI
Placebo	109.13	± 42.57
ISIS 443139 10 mg	143.65	± 49.74
ISIS 443139 30 mg	119.83	± 45.27
ISIS 443139 60 mg	116.70	± 30.46
ISIS 443139 90 mg	104.99	± 65.01
ISIS 443139 120 mg	95.87	± 35.11

Change from Baseline

Group	Value	95% CI
Placebo	4.08	± 28.47
ISIS 443139 10 mg	-31.28	± 25.71
ISIS 443139 30 mg	-31.98	± 24.96
ISIS 443139 60 mg	-30.83	± 17.17
ISIS 443139 90 mg	-45.76	± 27.65
ISIS 443139 120 mg	-38.41	± 21.59

Change From Baseline in CSF Neurofilament Light Chain Concentration Secondary · Baseline to Final Assessment (Day 85 or 113)

Baseline was defined as the last non-missing measure prior to the first dose.

Baseline

Group	Value	95% CI
Placebo	2774	± 767
ISIS 443139 10 mg	2697	± 1909
ISIS 443139 30 mg	2548	± 916
ISIS 443139 60 mg	2280	± 976
ISIS 443139 90 mg	2328	± 951
ISIS 443139 120 mg	2551	± 872

Change from Baseline

Group	Value	95% CI
Placebo	324	± 371
ISIS 443139 10 mg	77	± 223
ISIS 443139 30 mg	202	± 493
ISIS 443139 60 mg	274	± 301
ISIS 443139 90 mg	1161	± 2980
ISIS 443139 120 mg	628	± 1128

Ventricular Volume as Assessed by Structural Magnetic Resonance Imaging (MRI) Secondary · Screening, Days 113, and 197

Screening

Group	Value	95% CI
Placebo	35.58	± 19.02
ISIS 443139 10 mg	17.88	± 12.20
ISIS 443139 30 mg	33.02	± 17.46
ISIS 443139 60 mg	31.90	± 13.21
ISIS 443139 90 mg	39.33	± 23.52
ISIS 443139 120 mg	27.53	± 19.31

Day 113

Group	Value	95% CI
Placebo	36.11	± 19.37
ISIS 443139 10 mg	18.66	± 12.84
ISIS 443139 30 mg	33.56	± 17.87
ISIS 443139 60 mg	32.04	± 14.26
ISIS 443139 90 mg	42.24	± 25.80
ISIS 443139 120 mg	30.36	± 21.80

Day 197

Group	Value	95% CI
Placebo	36.46	± 18.97
ISIS 443139 10 mg	19.69	± 13.03
ISIS 443139 30 mg	34.82	± 18.16
ISIS 443139 60 mg	34.57	± 14.82
ISIS 443139 90 mg	44.43	± 27.37
ISIS 443139 120 mg	33.02	± 24.61

Huntington's Disease (HD) Cognitive Assessment Battery Composite Score Secondary · Baseline to Days 84, 141, and 197

The HD Cognitive Battery was developed as a means of measuring cognitive dysfunction in late premanifest and early manifest HD patients. The 6 tests that comprise the battery were selected based on test sensitivity, practice effects, reliability, domain coverage, feasibility for use in clinical trials, and tolerability. A composite cognitive score was calculated by the average z-score of the 6 individual tests. A positive change from baseline indicated improvement in cognitive function; a negative change indicated worsening. Baseline was defined as the last non-missing measure prior to the fir

Baseline

Group	Value	95% CI
Placebo	-0.0860	± 0.2941
ISIS 443139 10 mg	0.2979	± 0.5157
ISIS 443139 30 mg	0.0839	± 0.5108
ISIS 443139 60 mg	-0.0404	± 0.3976
ISIS 443139 90 mg	-0.1483	± 0.3284
ISIS 443139 120 mg	0.1212	± 0.3877

Change at Day 84

Group	Value	95% CI
Placebo	-0.0403	± 0.2261
ISIS 443139 10 mg	0.1314	± 0.3670
ISIS 443139 30 mg	-0.0430	± 0.3585
ISIS 443139 60 mg	-0.0338	± 0.2756
ISIS 443139 90 mg	0.1297	± 0.2560
ISIS 443139 120 mg	-0.0920	± 0.1668

Change at Day 141

Group	Value	95% CI
Placebo	0.0432	± 0.1829
ISIS 443139 10 mg	0.4441	± 0.8487
ISIS 443139 30 mg	-0.1065	± 0.2112
ISIS 443139 60 mg	-0.1792	± 0.2298
ISIS 443139 90 mg	0.2194	± 0.2224
ISIS 443139 120 mg	-0.0547	± 0.2136

Change at Day 197

Group	Value	95% CI
Placebo	-0.0778	± 0.2881
ISIS 443139 10 mg	0.4202	± 1.0482
ISIS 443139 30 mg	-0.0469	± 0.3151
ISIS 443139 60 mg	-0.1633	± 0.1170
ISIS 443139 90 mg	0.0827	± 0.2897
ISIS 443139 120 mg	-0.1387	± 0.2717

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to approximately 28 weeks. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo

Serious: 1/12 (8%)

Deaths: 0/12

ISIS 443139 10 mg

Serious: 0/3 (0%)

Deaths: 0/3

ISIS 443139 30 mg

Serious: 0/6 (0%)

Deaths: 0/6

ISIS 443139 60 mg

Serious: 0/6 (0%)

Deaths: 0/6

ISIS 443139 90 mg

Serious: 0/9 (0%)

Deaths: 0/9

ISIS 443139 120 mg

Serious: 0/10 (0%)

Deaths: 0/10

Serious adverse events (1 terms)

Reaction	System	Placebo	ISIS 443139 10 mg	ISIS 443139 30 mg	ISIS 443139 60 mg	ISIS 443139 90 mg	ISIS 443139 120 mg
Post lumbar puncture syndrome	Injury, poisoning and procedural complications	—	—	—	—	—	—

Other adverse events (87 terms — click to expand)

Reaction	System	Placebo	ISIS 443139 10 mg	ISIS 443139 30 mg	ISIS 443139 60 mg	ISIS 443139 90 mg	ISIS 443139 120 mg
Procedural pain	Injury, poisoning and procedural complications	—	—	—	—	—	—
Headache	Nervous system disorders	—	—	—	—	—	—
Post lumbar puncture syndrome	Injury, poisoning and procedural complications	—	—	—	—	—	—
Fall	Injury, poisoning and procedural complications	—	—	—	—	—	—
Nasopharyngitis	Infections and infestations	—	—	—	—	—	—
Upper respiratory tract infection	Infections and infestations	—	—	—	—	—	—
Skin abrasion	Injury, poisoning and procedural complications	—	—	—	—	—	—
Contusion	Injury, poisoning and procedural complications	—	—	—	—	—	—
Rhinitis	Infections and infestations	—	—	—	—	—	—
Influenza	Infections and infestations	—	—	—	—	—	—
Rhinovirus infection	Infections and infestations	—	—	—	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—
Fatigue	General disorders	—	—	—	—	—	—
Toothache	Gastrointestinal disorders	—	—	—	—	—	—
Haematoma	Vascular disorders	—	—	—	—	—	—
Joint injury	Injury, poisoning and procedural complications	—	—	—	—	—	—
Laceration	Injury, poisoning and procedural complications	—	—	—	—	—	—
Head injury	Injury, poisoning and procedural complications	—	—	—	—	—	—
Ligament sprain	Injury, poisoning and procedural complications	—	—	—	—	—	—
Muscle injury	Injury, poisoning and procedural complications	—	—	—	—	—	—
Muscle strain	Injury, poisoning and procedural complications	—	—	—	—	—	—
Tooth injury	Injury, poisoning and procedural complications	—	—	—	—	—	—
Upper limb fracture	Injury, poisoning and procedural complications	—	—	—	—	—	—
Bronchitis	Infections and infestations	—	—	—	—	—	—
Sinusitis	Infections and infestations	—	—	—	—	—	—
Urinary tract infection	Infections and infestations	—	—	—	—	—	—
Bronchopneumonia	Infections and infestations	—	—	—	—	—	—
Conjunctivitis	Infections and infestations	—	—	—	—	—	—
Gastrointestinal infection	Infections and infestations	—	—	—	—	—	—
Respiratory tract infection	Infections and infestations	—	—	—	—	—	—
Viral infection	Infections and infestations	—	—	—	—	—	—
Vulvovaginal candidiasis	Infections and infestations	—	—	—	—	—	—
Hypoaesthesia	Nervous system disorders	—	—	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—	—	—
Paraesthesia	Nervous system disorders	—	—	—	—	—	—
Tension headache	Nervous system disorders	—	—	—	—	—	—
Head discomfort	Nervous system disorders	—	—	—	—	—	—
Neuropathy peripheral	Nervous system disorders	—	—	—	—	—	—
Pleocytosis	Nervous system disorders	—	—	—	—	—	—

Most-reported serious reactions: Post lumbar puncture syndrome.

Data from ClinicalTrials.gov NCT02519036 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

Noncoding RNA therapeutics - challenges and potential solutions.
Winkle M, El-Daly SM, Fabbri M, Calin GA. · · 2021 · cited 1123× · PMID 34145432 · DOI 10.1038/s41573-021-00219-z
Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets.
Gao C, Jiang J, Tan Y, Chen S. · · 2023 · cited 998× · PMID 37735487 · DOI 10.1038/s41392-023-01588-0
Targeting Huntingtin Expression in Patients with Huntington's Disease.
Tabrizi SJ, Leavitt BR, Landwehrmeyer GB, Wild EJ, et al · · 2019 · cited 515× · PMID 31059641 · DOI 10.1056/nejmoa1900907
Advances in the delivery of RNA therapeutics: from concept to clinical reality.
Kaczmarek JC, Kowalski PS, Anderson DG. · · 2017 · cited 467× · PMID 28655327 · DOI 10.1186/s13073-017-0450-0
Chemistry, mechanism and clinical status of antisense oligonucleotides and duplex RNAs.
Shen X, Corey DR. · · 2018 · cited 455× · PMID 29240946 · DOI 10.1093/nar/gkx1239
Alternative splicing and cancer: a systematic review.
Zhang Y, Qian J, Gu C, Yang Y. · · 2021 · cited 358× · PMID 33623018 · DOI 10.1038/s41392-021-00486-7
Drug development in the era of precision medicine.
Dugger SA, Platt A, Goldstein DB. · · 2018 · cited 296× · PMID 29217837 · DOI 10.1038/nrd.2017.226
RNA-Based Therapeutics: From Antisense Oligonucleotides to miRNAs.
Bajan S, Hutvagner G. · · 2020 · cited 265× · PMID 31936122 · DOI 10.3390/cells9010137

Verify or expand the search:

Other recruiting trials for Huntington's Disease

Currently open trials in the same condition.

NCT07246941 — A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RG6496 in Huntington's Disease · Phase 1 · recruiting
NCT06585449 — A Study to Evaluate ALN-HTT02 in Adult Patients With Huntington's Disease · Phase 1 · recruiting
NCT02855476 — HDClarity: a Multi-site Cerebrospinal Fluid Collection Initiative to Facilitate Therapeutic Development for Huntington's · recruiting

Other Ionis Pharmaceuticals, Inc. trials

Trials by the same sponsor.

NCT06673069 — Hero: A Study to Evaluate the Safety, Tolerability, and Pharmacokinetics (PK) and Pharmacodynamics (PD) of ION269 in Par · Phase 1 · terminated
NCT06014541 — Observational Study to Characterize Biomarkers and Disease Progression in Participants With Methyl CpG Binding Protein 2 · terminated
NCT05610280 — A Study of Olezarsen (ISIS 678354) in Participants With Hypertriglyceridemia and Atherosclerotic Cardiovascular Disease, · Phase 3 · completed
NCT05579860 — A Study Comparing Two Subcutaneous Formulations: Vial and Autoinjector (AI) With Olezarsen, at Two Dose Levels, in Healt · Phase 1 · completed
NCT05552326 — A Study of Olezarsen Administered Subcutaneously to Participants With Severe Hypertriglyceridemia · Phase 3 · completed

Verify against primary sources

ClinicalTrials.gov — authoritative US registry record
WHO ICTRP — international registry index
EU Clinical Trials Register
Sponsor press releases (Google)

Data sources for this page

Trial protocol + status: ClinicalTrials.gov NCT02519036 (US National Library of Medicine, public domain)
Publications: Europe PMC API search by NCT ID, retrieved 10 June 2026
Drug + disease cross-links: matched in real time against Drug Landscape's normalised drug + company + condition tables
Sponsor: as reported to ClinicalTrials.gov by Ionis Pharmaceuticals, Inc.
Last refreshed: 31 May 2019

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT02519036.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing

NCT02519036

Quick facts

Drugs / interventions tested

Conditions studied

Sponsor

Who can join

Results — posted to ClinicalTrials.gov

Adverse events — posted to ClinicalTrials.gov

Serious adverse events (1 terms)

Sponsor's own description

Publications & conference data

Related trials

Other recruiting trials for Huntington's Disease

Other Ionis Pharmaceuticals, Inc. trials

Verify against primary sources