Overview

The ALSTARS trial will be conducted across 20-25 sites in the US and Canada, and will evaluate the safety and efficacy of an investigational treatment called COYA 302 for adults with Amyotrophic Lateral Sclerosis (ALS).

COYA 302 is an investigational and proprietary biologic combination therapy with a dual immunomodulatory mechanism of action intended to enhance the anti-inflammatory function of regulatory T cells (Tregs) and suppress the inflammation produced by activated monocytes and macrophages. It is comprised of low dose interleukin-2 (LD IL-2) and DRL_AB (a biosimilar candidate for abatacept). Participants will be randomly assigned to receive one of 2 regimens of COYA 302 or placebo (an inactive substance) for 24-weeks in the double-blind (DB) period. Those who complete this part of the study may be eligible to receive one of the two regimens of COYA 302 for an additional 24 weeks in a blinded active extension phase (EXT).

The study will assess changes in disease progression using established ALS clinical outcome measures, including the ALS Functional Rating Scale-Revised (ALSFRS-R), neurofilament (NfL), maximal inspiratory pressure (MIP), slow vital capacity (SVC), and neurological assessments. Additional objectives include evaluation of biomarkers and safety through routine clinical assessments and adverse event monitoring.

Eligibility

Key Inclusion Criteria:

1. Sporadic or familial ALS, diagnosed as clinically probable, lab-supported probable, or definite ALS according to the revised El Escorial criteria
2. Male or female participants aged 18 to 75
3. Time since onset of ALS symptoms ≤24 months from Screening. The qualifying first symptoms of ALS are limited to manifestations of weakness in extremity, bulbar, or respiratory muscles.
4. ALSFRS-R total score ≥35 at Screening with no individual items scored as 0 or 1.
5. Rate of progression at baseline between -0.5 and -1.5 points per month on ALSFRS-R total score.
6. SVC ≥70% of predicted capacity.
7. Participants receiving riluzole must be on a stable dose for at least 30 days prior to Screening, with intent to stay on stable dosage throughout the study. If not on a stable dose of riluzole for at least 30 days prior to Screening, willing to refrain from initiation of the agent for the duration of the trial.
8. Participants receiving edaravone (intravenous [IV] or oral, RADICAVA®) must have completed at least one treatment cycle prior to Screening, with intent to remain on stable dosage throughout the study. If participant has not completed at least one treatment cycle of edaravone at the time of Screening, willing to refrain from initiation of the agent for the duration of the trial.
9. Participants receiving tofersen (QALSODY®) must have completed 90 days of treatment prior to Screening, with intent to remain on stable dosage throughout the study. If participant has not completed at least 90 days of tofersen at the time of Screening, willing to refrain from initiation of the agent for the duration of the trial.

Key Exclusion Criteria:

1. Any clinically significant and/or unstable medical (including active systemic infections requiring treatment), surgical, or psychiatric condition or laboratory abnormality other than ALS, in the judgement of the Investigator.
2. Active suicidality (e.g., any suicide attempts within the past 12 months or any current suicidal intent, including a plan, as assessed by the C-SSRS, score of "YES" on questions 4 or 5; and/or based on clinical evaluation by the Investigator).
3. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels greater than 3 times the upper limit of normal (ULN).
4. Significant renal impairment as determined by estimated glomerular filtration rate (eGFR) of <60 mL/min.
5. Pre-existing chronic obstructive pulmonary disease or significant pulmonary impairment including those with an FEV1 ≤ 2 liters or < 75% predicted for height and age, in the judgement of the Investigator.
6. Clinically significant history of cardiac function impairment including cardiac ejection fraction below 40%, ventricular wall motion abnormalities, or coronary artery disease.
7. Any organ allografts.
8. A positive tuberculosis (TB) test indicating a latent TB infection or a positive test for viral hepatitis.
9. Currently receiving or have received abatacept treatment within 75 days prior to Screening.
10. Currently receiving or have received interleukin-2 (IL-2) treatment within 30 days prior to Screening.
11. Currently receiving or expected to receive immunosuppressant therapy (e.g., cyclosporine, sirolimus, tacrolimus, mycophenolate mofetil, systemic steroids) or antihypertensives over the course of the study.
12. Planning to receive a live vaccine during the study or within 3 months of discontinuation.
13. Current participation in another interventional clinical trial and/or participation in any investigational medication or device clinical trial within 30 days prior to Screening or 5 half-lives of elimination of the investigational medication, whichever is longer.
14. Previous participation in any COYA 302 (LD rhIL-2 and DRL_AB) study.
15. Pre-existing autoimmune condition.
16. Presence of an indwelling central catheter.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.