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

Ionis Pharmaceuticals

Status and phase: Completed; Phase 2; Phase 1

Conditions: Huntington's Disease

Treatments: Drug: ISIS 443139 60 mg; Drug: ISIS 443139 30 mg; Other: Placebo; Drug: ISIS 443139 120 mg; Drug: ISIS 443139 10 mg; Drug: ISIS 443139 90 mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT02519036

2015-000381-66 (EudraCT Number)

ISIS 443139-CS1

Details and patient eligibility

About

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.

Enrollment: 46 patients

Sex: All

Ages: 25 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• 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

Key Exclusion Criteria:

• 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 design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

46 participants in 6 patient groups, including a placebo group

ISIS 443139 10 mg

Experimental group

Description:

Participants received ISIS 443139, 10 milligrams (mg), by intrathecal injection, on Study Days 1, 29, 57, and 85.

Treatment:

Drug: ISIS 443139 10 mg

ISIS 443139 30 mg

Experimental group

Description:

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

Treatment:

Drug: ISIS 443139 30 mg

ISIS 443139 60 mg

Experimental group

Description:

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

Treatment:

Drug: ISIS 443139 60 mg

ISIS 443139 90 mg

Experimental group

Description:

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

Treatment:

Drug: ISIS 443139 90 mg

ISIS 443139 120 mg

Experimental group

Description:

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

Treatment:

Drug: ISIS 443139 120 mg

Placebo

Placebo Comparator group

Description:

Participants received placebo, by intrathecal injection, on Study Days 1, 29, 57, and 85.

Treatment:

Other: Placebo