Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of IONIS-MAPTRx in Patients With Mild Alzheimer's Disease

Ionis Pharmaceuticals

Status and phase: Completed; Phase 1

Conditions: Mild Alzheimer's Disease

Treatments: Drug: IONIS MAPTRx; Other: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT03186989

ISIS 814907-CS1

2016-002713-22 (EudraCT Number)

NL60032.000.16 (Other Identifier)

Details and patient eligibility

About

The purpose of this study was to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of IONIS-MAPTRx in patients with Mild Alzheimer's Disease.

Full description

This was a randomized, double-blind, placebo-controlled study in 46 participants, followed by an Open-Label Extension. This study consisted of two parts:

Part 1: a randomized, double-blind, placebo-controlled multiple ascending dose period in participants with Mild Alzheimer's Disease, followed by Part 2: the open-label, long-term extension period.

Enrollment: 46 patients

Sex: All

Ages: 50 to 74 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria for Part 1:

• Males or females aged 50-74 years, inclusive, at the time of informed consent
• Diagnosed with mild Alzheimers disease, including CSF biomarkers consistent with this diagnosis
• Body Mass Index BMI ≥ 18 and ≤ 35 kg/m2 and total body weight > 50 kg (110 lbs)
• Able and willing to meet all study requirements, including toleration for MRI scans, blood draws and lumbar punctures, 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 patient to select trial visits and to be available to the Study Center by phone if needed
• Reside within 4 hours travel of the Study Center

Exclusion Criteria for Part 1:

• Treatment with another Study Drug, biological agent, or device within one-month of Screening or 5 half-lives of investigational agent, whichever is longer
• Clinically significant medical condition which would make the patient unsuitable for inclusion or could interfere with the patient participating in or completing the study
• Use of a disallowed CNS-active or antipsychotic medication within 4 weeks prior to Screening punctures

Inclusion Criteria for Part 2:

• Must have completed the Treatment Evaluation and Post-Treatment Periods in Part 1

Exclusion Criteria for Part 2 (only applicable to participants in Cohorts A and B, as participants from Cohorts C and D will seamlessly transition to Part 2):

• Treatment with another Study Drug, biological agent, or device within one-month of Screening or 5 half-lives of investigational agent, whichever is longer
• Clinically significant medical condition which would make the patient unsuitable for inclusion or could interfere with the patient participating in or completing the study
• Use of a disallowed CNS-active or antipsychotic medication within 4 weeks prior to Screening punctures

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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46 participants in 11 patient groups, including a placebo group

Part 1: Cohort A: ISIS 814907 10 mg

Experimental group

Description:

Participants received 10 milligrams (mg) ISIS 814907 diluted in 20 milliliters (mL) artificial cerebrospinal fluid (CSF), intrathecally, every four weeks (Q4W) on Days 1, 29, 57, and 85 in Part 1 of the study.

Treatment:

Drug: IONIS MAPTRx

Part 1: Cohort B: ISIS 814907 30 mg

Experimental group

Description:

Participants received 30 mg ISIS 814907 diluted in 20 mL in artificial CSF, intrathecally, Q4W on Days 1, 29, 57, and 85 in Part 1 of the study.

Treatment:

Drug: IONIS MAPTRx

Part 1: Cohort C: ISIS 814907 60 mg

Experimental group

Description:

Participants received 60 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q4W on Days 1, 29, 57, and 85 in Part 1 of the study.

Treatment:

Drug: IONIS MAPTRx

Part 1: Cohort D: ISIS 814907 115 mg

Experimental group

Description:

Participants received 115 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, every 12 weeks (Q12W) on Days 1 and 85 in Part 1 of the study.

Treatment:

Drug: IONIS MAPTRx

Part 1: Pooled Placebo

Placebo Comparator group

Description:

Participants received 20 mL artificial CSF, intrathecally, as placebo on Days 1, 29, 57, and 85 for the 4-dose regimens, or on Days 1 and 85 for the 2-dose regimens in Part 1 of the study.

Treatment:

Other: Placebo

Part 2: Late Start Cohort A + Cohort B + Cohort C + ISIS 814907 60 mg

Experimental group

Description:

Participants from MAD Cohorts A, B, C that were placebo-treated, received 60 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q12W on Days 1, 85, 169, 253, and 337 in Part 2 of the study.

Treatment:

Drug: IONIS MAPTRx

Part 2: Late Start Cohort D + ISIS 814907 115 mg

Experimental group

Description:

Participants from MAD Cohort D that were placebo-treated, received 115 mg ISIS 814907 diluted up in 20 mL artificial CSF, intrathecally, Q12W on Days 1, 85, 169, 253, and 337 in Part 2 of the study.

Treatment:

Drug: IONIS MAPTRx

Part 2: Early Start Cohort A + ISIS 814907 60 mg

Experimental group

Description:

Participants from MAD Cohort A that were ISIS 814907 10 mg -treated, received 60 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q12W on Days 1, 85, 169, 253, and 337 in Part 2 of the study.

Treatment:

Drug: IONIS MAPTRx

Part 2: Early Start Cohort B + ISIS 814907 60 mg

Experimental group

Description:

Participants from MAD Cohort B that were ISIS 814907 30 mg-treated, received 60 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q12W on Days 1, 85, 169, 253, and 337 in Part 2 of the study.

Treatment:

Drug: IONIS MAPTRx

Part 2: Early Start Cohort C + ISIS 814907 60 mg

Experimental group

Description:

Participants from MAD Cohort C that were ISIS 814907 60 mg-treated, received 60 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q12W on Days 1, 85, 169, 253, and 337 in Part 2 of the study.

Treatment:

Drug: IONIS MAPTRx

Part 2: Early Start Cohort D + ISIS 814907 115 mg

Experimental group

Description:

Participants from MAD Cohort D that were ISIS 814907 115 mg-treated, received 115 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q12W on Days 1, 85, 169, 253, and 337 in Part 2 of the study.

Treatment:

Drug: IONIS MAPTRx