Clinical trial NCT05695521: Regulatory T Cells for Amyotrophic Lateral Sclerosis
Official title: Phase 1 Safety Run-in Study and Phase 1b Randomized, Double Blinded, Placebo Controlled Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Amyotrophic Lateral Sclerosis
Keywords: ALS
Cellenkos
T Regulatory Cells
Randomized Placebo Control Trial
Umbilical cord blood
Amyotrophic Lateral Sclerosis
Lead sponsor: Cellenkos, Inc.
Sponsor class: INDUSTRY
First posted: 2023-01-25
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Maximum age (years): 95
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a randomized two-arm, multi-center phase Ib trial of CK0803 (cryopreserved, allogeneic, cord blood derived T regulatory cells that express neurotropic homing markers) versus placebo for treatment of adults with amyotrophic lateral sclerosis (ALS) having onset within 5 years of trial entry. This trial will consist of a 6-patient safety run-in followed by a randomized comparative trial with up to two stages (stages 1 and 2), each stage of size 30 patients, with a safety rule applied after stage 1 that may terminate the trial early, for a maximum total sample size of 6+30+30 = 66 patients.
Primary purpose: TREATMENT

Brief summary: Phase 1 Safety Run-in Study of 6 patients followed by Phase 1b Randomized, Double Blind, Placebo Control Trial of CK0803, neurotropic, allogeneic, umbilical cord blood derived T regulatory (Treg) cells in additional 60 patients with Amyotrophic Lateral Sclerosis.

Detailed description: CK0803, neurotrophic allogenic T regulatory Cells (Treg), utilizes Cellenkos' proprietary CRANE technology to generate disease specific products. The primary objective of the upcoming phase 1 study is to establish safety and tolerability of multiple doses of CK0803 in ALS patients. The goal of the phase 1b study is to extend safety and establish efficacy of CK0803 in ALS using the combined assessment of function and survival (CAFS) that ranks patients' clinical outcomes based on survival time and change in the ALS Functional Rating Scale-Revised (ALSFRS-R) score.

Eligibility criteria: Inclusion Criteria:

* Ability of the subject or his/her legally authorized representative to provide informed consent.
* Adult ALS subjects (≥18 years of age)
* Diagnosis of ALS, according to the Revised El Escorial Criteria for ALS
* Subjects with disease onset ≤ 5 years
* Upright (sitting position) Slow Vital Capacity (SVC) as adjusted for sex, age and height ≥ 50% predicted
* Subjects must have documented ALSFRSR score of 36-45 at baseline.
* Subjects taking concomitant Riluzole or Edaravone or Albrioza at study entry must be on a stable dose for ≥ 30 days prior to the first dose of study treatment (Day 1).
* Screening values of coagulation parameters including platelet count, international normalized ratio (INR), prothrombin time (PT), and activated partial thromboplastin time (APTT) should be within normal ranges.
* Agree to practice highly effective contraception during the study and continue contraception for 90 days after their last dose of study treatment.

Exclusion Criteria:

* Uncontrolled infection, not responding to appropriate antimicrobial agents after seven days of therapy. The Protocol medical monitor is the final arbiter of eligibility.
* Antiplatelet or anticoagulant therapy within the 14 days prior to Day 1 or anticipated use during the study, including but not limited to daily aspirin including low dose aspirin (defined as ≤ 150 mg/day), clopidogrel, dipyridamole, warfarin, dabigatran, rivaroxaban and apixaban
* Clinically significant low platelet count (defined as \< 100,000/mm3), coagulation tests, or laboratory abnormalities that would render a subject unsuitable for inclusion
* Unwillingness to comply with study procedures, including follow-up, as specified by this protocol, or unwillingness to cooperate fully with the Investigator
* Have any other conditions, which, in the opinion of the Investigator would make the subject unsuitable for inclusion, or could interfere with the subject participating in or completing the study
* Concurrent participation in any other interventional clinical study
* Treatment with another investigational drug, biological agent, or device, including, but not limited to sodium phenylbutyrate, within 1 month of Screening, or 5 half-lives of investigational agent, whichever is longer
* Treatment of cancer in the last 5 years (except in situ carcinoma of the cervix or basal cell carcinoma)
* Female subjects who are pregnant or currently breastfeeding
* Other unspecified reasons that, in the opinion of the Investigator or Sponsor, make the subject unsuitable for enrollment.

Primary outcomes:
measure: Treatment Limiting Toxicity (TLT)
timeFrame: 28 days
measure: Combined assessment of function and survival (CAFS)
timeFrame: 24 weeks
Secondary outcomes:
measure: Incidence of all cause AEs and SAEs
timeFrame: baseline and at weeks 1, 2, 3, 4, 5, 8, 12 and/or 13, 16, 20, 24 and/or 25, 36 and 48 from first infusion and/or at end of treatment (EOT)
measure: ALS Functional Rating Scale-Revised (ALSFRS-R) Score
timeFrame: Each measured at baseline and at weeks 5, 8, 12 and/or 13, 16, 20, 24 and/or 25, 36 and 48 from first infusion and/or at EOT
measure: Amyotrophic Lateral Sclerosis Specific Quality of Life - Revised (ALSSQOL-R)
timeFrame: Each measured at baseline and at weeks 5, 8, 12 and/or 13, 16, 20, 24 and/or 25, 36 and 48 from first infusion and/or at EOT
measure: Slow Vital Capacity (SVC)
timeFrame: Each measured at baseline and at weeks 5, 8, 12 and/or 13, 16, 20, 24 and/or 25, 36 and 48 from first infusion and/or at EOT
measure: Handheld dynamometer (HHD)
timeFrame: Each measured at baseline and at weeks 5, 8, 12 and/or 13, 16, 20, 24 and/or 25, 36 and 48 from first infusion and/or at EOT
measure: Nfl CSF
timeFrame: Each measured at baseline and at weeks 5, 8, 12 and/or 13, 16, 20, 24 and/or 25, 36 and 48 from first infusion and/or at EOT
measure: Nfl Serum
timeFrame: Each measured at baseline and at weeks 5, 8, 12 and/or 13, 16, 20, 24 and/or 25, 36 and 48 from first infusion and/or at EOT12 months
measure: Ventilation assistance-free survival (VAFS)
timeFrame: Each measured at baseline and at weeks 5, 8, 12 and/or 13, 16, 20, 24 and/or 25, 36 and 48 from first infusion and/or at EOT
measure: Overall Survival (OS)
timeFrame: 24 weeks and 48 weeks from first infusion and/or at EOT
Other outcomes:
Locations:
city: New York
country: United States
facility: Columbia University Irving Medical Center
state: New York
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: Michael E. DeBakey Veterans Affairs Medical Center
state: Texas
Study officials:
affiliation: Columbia University
name: Neil Shneider, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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