A Study of Single Ascending Doses of NI112 in Adults With Amyotrophic Lateral Sclerosis (ALS)

NCT07906665 · tracked via the Priya Life Science USA tracker

Sponsor

Sachi Bioworks Inc

Phase

Phase 1

Started

2027-01-22

Last updated

2026-10-30

Condition(s) studied

Amyotrophic Lateral Sclerosis (ALS)

Investigational drug(s) / intervention(s)

NI112Placebo

NI112: Antisense Nanoligomer administered at 40 mg/mL, as a single subcutaneous injection on Day 1. Doses above 40 mg are divided across two injection sites with no more than 1.5 mL per site.

Placebo: Sterile normal saline (0.9% sodium chloride), administered as a single subcutaneous injection on Day 1.

Study summary

This is a first-in-human study of NI112, an investigational medicine given as an injection under the skin, in adults with amyotrophic lateral sclerosis (ALS). The purpose of the study is to find out how safe NI112 is, how well it is tolerated, and how the body handles it after a single dose. Up to 40 adults with ALS will take part at up to three study centers in the United States. Participants will be assigned by chance to receive either a single dose of NI112 or a single dose of placebo (sterile salt water). The study tests up to seven dose levels, one after another, beginning with the lowest dose. A Safety Review Board reviews the safety information from each group of participants before the next, higher dose is given to a new group. Each participant stays in the hospital for 24 hours after the injection for safety monitoring and blood sampling, and returns for follow-up visits on Day 8 and Day 28. The study also measures the amount of NI112 in blood and in spinal fluid.

Eligibility

Sex

ALL

Min age

18 Years

Max age

—

Healthy volunteers

Inclusion Criteria: * • Able to understand the purpose and risks of the study and to provide signed, dated informed consent and authorization for use of protected health information. A legally authorized representative may consent if the subject is legally unable to do so. * Aged ≥ 18 years at the time of informed consent. No upper age limit. * Weakness attributable to ALS and a diagnosis of possible, laboratory-supported probable, probable or definite ALS per the revised El Escorial criteria (Airlie House, 1998). * Forced vital capacity ≥ 50% of predicted, adjusted for sex, age, height and sitting position. Subjects with a stable forced vital capacity of 45 to 49% with no more than 5% decline over 6 months may be eligible at the Investigator's discretion. * If taking riluzole, on a stable dose for more than 30 days before Day 1 and expected to remain on that dose through study completion. * Medically able to undergo the study procedures and to adhere to the visit schedule and study restrictions, as determined by the Investigator. * Screening platelet count, INR, PT and APTT within normal limits. A single repeat test is allowed if initial values are marginally abnormal, per Investigator judgment. * Sexually active females of childbearing potential and non-sterile males must agree to use effective contraception during the study and for 90 days after the final dose. Males, including those who have had a vasectomy, with a pregnant partner must use a condom from the first dose and for 90 days after, and must not donate sperm for 90 days after the final dose. Exclusion Criteria: * • Positive test for, or history of, human immunodeficiency virus. * Positive test for, or history of, hepatitis C antibody, or hepatitis B (positive for both surface antigen and core antibody). * Prior treatment with another investigational drug, biologic or device within 1 month or 5 half-lives, whichever is longer. Prior use of siRNA, stem cell therapy or gene therapy is prohibited. * Currently enrolled in another interventional study. * Current or anticipated need for a diaphragm pacing system, per Investigator judgment. * History of drug or alcohol abuse within 6 months that may interfere with study participation. * Presence of a tracheostomy. * Known active infection requiring systemic antiviral or antimicrobial therapy during screening. * An ongoing medical condition, for example cachexia or severe anemia, that may interfere with study conduct or assessments. * Pregnancy or breastfeeding at screening or at admission. * Significant cognitive impairment, clinical dementia, or unstable psychiatric illness, for example psychosis, suicidal ideation, suicide attempt, or untreated major depression within 90 days. * History of broad anesthetic allergies. * Increased or uncontrolled bleeding risk, including anatomical abnormalities near the lumbar puncture site or coagulation disorders. * Anticipated need for antiplatelet or anticoagulant therapy within 7 days before or 48 hours after lumbar puncture. * Presence of an implanted cerebrospinal fluid shunt or central nervous system catheter. * Clinically significant hematology or chemistry abnormalities, per Investigator judgment. * Significant ECG abnormalities, including QTcF greater than 450 ms in males or greater than 460 ms in females. * Estimated glomerular filtration rate below 60 mL/min/1.73 m2 at screening by the CKD-EPI equation, or known chronic kidney disease stage 3 or above, nephrotic syndrome, or chronic glomerulonephritis. * AST or ALT greater than 2 times the upper limit of normal at screening; or total bilirubin greater than 1.5 times the upper limit of normal at screening, except in Gilbert syndrome; or known cirrhosis, chronic active hepatitis or hepatic insufficiency. * Known hypersensitivity, allergy or adverse reaction to gold or gold-containing compounds. NI112 contains gold nanoparticles. * Currently receiving tofersen, or received tofersen within 6 months before screening. * Inability to comply with study requirements. * Any other condition or circumstance deemed unsuitable by the Investigator or Sponsor.

Primary outcome measure(s)

Number of Participants With incidence and severity of treatment-emergent adverse events — Day 1 through Day 28
Number and percentage of participants with treatment-emergent adverse events, graded by severity according to NCI CTCAE version 5.0.
Number of Participants With incidence and severity of treatment-emergent serious adverse events — Day 1 through Day 28
Number and percentage of participants with treatment-emergent serious adverse events, graded by severity according to NCI CTCAE version 5.0.
Number of Participants With Treatment-Emergent Clinically Significant Blood Pressure Abnormalities — Day 1 through Day 28
Systolic and diastolic blood pressure, in mmHg, measured at screening, predose on Day 1, within one hour before the 2-hour and 4-hour postdose pharmacokinetic blood draws on Day 1, at 24 hours postdose on Day 2, on Day 8 and on Day 28. A value or finding is counted as clinically significant where it is newly present after dosing and the Investigator records it as clinically significant, applying the protocol definition: a finding that meets serious adverse event criteria, necessitates specific corrective therapy, or is deemed clinically significant by the Investigator. The single reported value is the NUMBER OF PARTICIPANTS with at least one such finding, by treatment arm.
Number of Participants With Treatment-Emergent Clinically Significant Pulse Rate Abnormalities — Day 1 through Day 28
Pulse rate, in beats per minute, measured at screening, predose on Day 1, within one hour before the 2-hour and 4-hour postdose pharmacokinetic blood draws on Day 1, at 24 hours postdose on Day 2, on Day 8 and on Day 28. A value or finding is counted as clinically significant where it is newly present after dosing and the Investigator records it as clinically significant, applying the protocol definition: a finding that meets serious adverse event criteria, necessitates specific corrective therapy, or is deemed clinically significant by the Investigator. The single reported value is the NUMBER OF PARTICIPANTS with at least one such finding, by treatment arm.
Number of Participants With Treatment-Emergent Clinically Significant Respiratory Rate Abnormalities — Day 1 through Day 28
Respiratory rate, in breaths per minute, measured at screening, predose on Day 1, within one hour before the 2-hour and 4-hour postdose pharmacokinetic blood draws on Day 1, at 24 hours postdose on Day 2, on Day 8 and on Day 28. A value or finding is counted as clinically significant where it is newly present after dosing and the Investigator records it as clinically significant, applying the protocol definition: a finding that meets serious adverse event criteria, necessitates specific corrective therapy, or is deemed clinically significant by the Investigator. The single reported value is the NUMBER OF PARTICIPANTS with at least one such finding, by treatment arm.
Number of Participants With Treatment-Emergent Clinically Significant Body Temperature Abnormalities — Day 1 through Day 28
Body temperature, in °C, measured at screening, predose on Day 1, within one hour before the 2-hour and 4-hour postdose pharmacokinetic blood draws on Day 1, at 24 hours postdose on Day 2, on Day 8 and on Day 28. A value or finding is counted as clinically significant where it is newly present after dosing and the Investigator records it as clinically significant, applying the protocol definition: a finding that meets serious adverse event criteria, necessitates specific corrective therapy, or is deemed clinically significant by the Investigator. The single reported value is the NUMBER OF PARTICIPANTS with at least one such finding, by treatment arm.
Number of Participants With Treatment-Emergent Clinically Significant Neurological Examination Findings — Day 1 through Day 8
A neurological examination is performed at screening, predose on Day 1, at 3 hours and 6 hours postdose on Day 1, at 24 hours postdose on Day 2, and on Day 8. A value or finding is counted as clinically significant where it is newly present after dosing and the Investigator records it as clinically significant, applying the protocol definition: a finding that meets serious adverse event criteria, necessitates specific corrective therapy, or is deemed clinically significant by the Investigator. The single reported value is the NUMBER OF PARTICIPANTS with at least one such finding, by treatment arm.
Number of Participants With Treatment-Emergent Clinically Significant Physical Examination Findings — Day 1 through Day 8
A physical examination is performed at screening and predose on Day 1. A limited physical examination is performed at 24 hours postdose on Day 2 and on Day 8, at the Investigator's discretion. A value or finding is counted as clinically significant where it is newly present after dosing and the Investigator records it as clinically significant, applying the protocol definition: a finding that meets serious adverse event criteria, necessitates specific corrective therapy, or is deemed clinically significant by the Investigator. The single reported value is the NUMBER OF PARTICIPANTS with at least one such finding, by treatment arm.
Number of Participants With Treatment-Emergent Clinically Significant 12-Lead Electrocardiogram Abnormalities, Including QT Interval Corrected by Fridericia's Formula (QTcF) — Day 1 through Day 28
Triplicate 12-lead electrocardiograms are recorded after the participant has rested supine for at least 10 minutes, at screening, predose on Day 1, within one hour before the 2-hour and 4-hour postdose pharmacokinetic blood draws on Day 1, at 24 hours postdose on Day 2, on Day 8 and on Day 28. The first recording is interpreted and the remaining two are checked for consistency and quality. The QT interval is corrected by Fridericia's formula and reported in milliseconds. A QTcF above 500 ms, or an increase from baseline above 60 ms, meets a protocol-defined dose-limiting toxicity criterion. A value or finding is counted as clinically significant where it is newly present after dosing and the Investigator records it as clinically significant, applying the protocol definition: a finding that meets serious adverse event criteria, necessitates specific corrective therapy, or is deemed clinically significant by the Investigator. The single reported value is the NUMBER OF PARTICIPANTS wit
Number of Participants With Treatment-Emergent Clinically Significant Hematology Abnormalities — Day 1 through Day 28
Hematology comprises a complete blood count with differential, platelet count and absolute neutrophil count, collected at screening, predose on Day 1, at 24 hours postdose on Day 2, on Day 8 and on Day 28, and analyzed by a designated central laboratory. Coagulation testing (platelet count, international normalized ratio, prothrombin time and activated partial thromboplastin time) is performed at screening only. A laboratory value is counted as clinically significant where, per the protocol, it meets serious adverse event criteria, necessitates specific corrective therapy, or is deemed clinically significant by the Investigator. The single reported value is the number of participants with at least one such value, by treatment arm.
Number of Participants With Treatment-Emergent Clinically Significant Serum Chemistry Abnormalities — Day 1 through Day 28
Serum chemistry comprises electrolytes, total protein, albumin, creatinine, blood urea nitrogen, uric acid, total and direct bilirubin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, glucose, calcium, phosphorus, bicarbonate, chloride, sodium and potassium, collected at screening, predose on Day 1, at 24 hours postdose on Day 2, on Day 8 and on Day 28, and analyzed by a designated central laboratory. A laboratory value is counted as clinically significant where, per the protocol, it meets serious adverse event criteria, necessitates specific corrective therapy, or is deemed clinically significant by the Investigator. The single reported value is the number of participants with at least one such value, by treatment arm.
Number of Participants With Treatment-Emergent Clinically Significant Urinalysis Abnormalities — Day 1 through Day 28
Urinalysis is performed by dipstick testing for blood, protein and glucose, with microscopic examination where an abnormality is detected, at screening, predose on Day 1, at 24 hours postdose on Day 2, on Day 8 and on Day 28, analyzed by a designated central laboratory. A finding is counted as clinically significant where, per the protocol, it meets serious adverse event criteria, necessitates specific corrective therapy, or is deemed clinically significant by the Investigator. The single reported value is the number of participants with at least one such finding, by treatment arm.
Number of Participants With discontinuations due to adverse events — Day 1 through Day 28
Number and percentage of participants discontinuing study intervention or withdrawing from the study because of an adverse event.
Maximum tolerated dose of single-dose NI112 — From the first dose of the first cohort through the Day 28 visit of the last subject in the highest cohort evaluated, approximately 13 months
The maximum tolerated dose identified by the Safety Review Board applying the pre-specified dose-escalation and stopping criteria together with clinical judgment.

Trial sites (3)

Facility	City	Region
Mayo Clinic Arizona, Scottsdale, AZ	Scottsdale	Arizona
Mayo Clinic Florida, Jacksonville	Jacksonville	Florida
Mayo Clinic Rochester, Rochester, MN	Rochester	Minnesota

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Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT07906665 on ClinicalTrials.gov ↗ ← All trials in the USA