A Phase 1 Study to Investigate the Safety and Pharmacokinetics of ABBV-CLS-7262 in Patients With Amyotrophic Lateral Sclerosis

Study Overview
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Brief Summary
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ABBV-CLS-7262 is an investigational drug being researched for the treatment of Amyotrophic Lateral Sclerosis. This is an up to 156-week, 2-part study. Part 1 will be a 4-week, randomized, double-blind, placebo-controlled study; Part 2 will be up to a 152-week active treatment extension (ATE) during which all subjects will receive ABBV-CLS-7262.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled Study to Assess Safety, Tolerability, and Pharmacokinetics Following Multiple Doses of ABBV-CLS-7262 in Subjects With Amyotrophic Lateral Sclerosis Followed by an Active Treatment Extension

Conditions
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ALS, Amyotrophic Lateral Sclerosis

Intervention / Treatment
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* Drug: ABBV-CLS-7262
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must have an identified, reliable caregiver Confirmed diagnosis of Familial ALS or Sporadic ALS First ALS symptoms occurred ≤36 months before screening Able to swallow solids No known active COVID-19 infection at screening Vital capacity ≥50% predicted value (for sex, age, ethnic origin, and height) at screening If taking concomitant standard-of-care medications approved for the treatment of ALS (or their components), subjects must be on a stable dose of the medication(s) for >30 days prior to Baseline in order to enter the study. For edaravone, a stable dose is defined by having completed 2 treatment cycles prior to Baseline. Exclusion Criteria: History of dementia/severe cognitive problems at screening History of clinically significant medical conditions (other than ALS) or any other reason, including any physical, psychological, or psychiatric condition that, in the opinion of the Investigator, would compromise the safety or interfere with the subject's participation in the study, or would make the subject an unsuitable candidate to receive study drug, or would put the subject at risk by participating in the study. History of abnormal screening laboratory or imaging results that, in the opinion of the Investigator, are indicative of any significant cardiac, endocrinologic, hematologic, hepatic, immunologic, infectious, metabolic, urologic, pulmonary, gastrointestinal, dermatologic, psychiatric, renal, neurologic, and/or other major disease that would preclude administration of ABBV-CLS-7262. Documented active or suspected malignancy or history of any malignancy within the last 5 years except for successfully treated non-melanoma skin cancer or localized carcinoma in situ of the cervix If female, is known to be pregnant, breastfeeding, considering becoming pregnant, or donating/banking eggs during the study or within 30 days or >5 half-lives (whichever is longer) after the last dose of study drug If male, plans to donate sperm or father a child during the study or within 30 days after the last dose of study drug Known to have received any investigational product within 30 days or 5 half-lives of the drug (whichever is longer) prior to the first dose of study drug or is currently enrolled in another clinical study History of ABBV-CLS-7262 use prior to participation in this study Recent (within 6 months prior to Screening) history of drug or alcohol abuse Previous participation in a stem cell clinical study for treatment of ALS Current or anticipated use of diaphragmatic pacing during the study period Tracheostomy or use of non-invasive ventilatory support ≥22 hours a day

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ABBV-CLS-7262 LOW DOSE<br> | Drug: ABBV-CLS-7262<br>* Oral<br>|
| Active Comparator: ABBV-CLS-7262 MEDIUM DOSE<br> | Drug: ABBV-CLS-7262<br>* Oral<br>|
| Active Comparator: ABBV-CLS-7262 HIGH DOSE<br> | Drug: ABBV-CLS-7262<br>* Oral<br>|
| Placebo Comparator: PLACEBO<br> | Drug: Placebo<br>* Oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability | Number of patients with treatment-related adverse events as assessed by CTCAE v4.03 | Baseline Up to Approximately Day 28 | 
| Pharmacokinetics | Maximum Plasma Concentration [Cmax] | Baseline Up to Approximately Day 28 | 
| Pharmacokinetics | Area Under the Curve [AUC] | Baseline Up to Approximately Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CSF Pharmacokinetics | Concentration at steady state in CSF | Baseline Up to Approximately Day 28 | 
| Safety and Tolerability | Number of patients with treatment-related adverse events as assessed by CTCAE v4.03 | Baseline Up to Approximately Week 156 |