Amyotrophic Lateral Sclerosis (ALS)Phase 1NCT07906665
A Study of Single Ascending Doses of NI112 in Adults With Amyotrophic Lateral Sclerosis (ALS)
A Phase 1 study testing NI112 in people with Amyotrophic Lateral Sclerosis (ALS), run by Sachi Bioworks Inc. at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Amyotrophic Lateral Sclerosis (ALS)
- What is being tested?
- NI112
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 3 sitesUnited States
- Study dates
- 22 Jan 2027to 1 Mar 2028
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- • 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.
Who cannot join
- • 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.
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- 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.
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States3 sites
Mayo Clinic Florida, Jacksonville
Jacksonville, Florida, 32224
Prashant Nagpal, 720-361-2159, nagpal@sachibio.com
Bjorn Oskarsson, M.D., FAAN
Mayo Clinic Rochester, Rochester, MN
Rochester, Minnesota, 55905
Prashant Nagpal, 720-361-2159, nagpal@sachibio.com
Nathan P. Staff, M.D., Ph.D.
Mayo Clinic Arizona, Scottsdale, AZ
Scottsdale, Arizona, 85259
Prashant Nagpal, 720-361-2159, nagpal@sachibio.com
Stephen A. Johnson, M.D.
About this study
Official title: Phase 1 Placebo-Controlled Study of NI112 in Adults With Amyotrophic Lateral Sclerosis (ALS): Evaluation of Safety, Tolerability, and Pharmacokinetics of Single Ascending Doses
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.
Read the detailed description
This is a Phase 1, first-in-human, multi-center, randomized, double-blind, placebo-controlled, sequential single ascending dose-escalation study evaluating the safety, tolerability and pharmacokinetics of NI112 administered by subcutaneous injection to adults with amyotrophic lateral sclerosis. Up to seven sequential dose cohorts are planned at 2.5, 5, 10, 20, 40, 80 and 120 mg. Cohorts at 20 mg and below enroll 4 subjects randomized 3 active to 1 placebo; cohorts above 20 mg enroll 8 subjects randomized 6 active to 2 placebo. The 5 mg cohort may be omitted only under pre-specified pharmacokinetic criteria. The Safety Review Board may expand any of the first four cohorts to a maximum of 8 subjects, and total enrollment will not exceed 40 subjects. Within each new dose level the first two subjects, one active and one placebo, are dosed at least 48 hours apart and the Safety Review Board reviews all available safety data for that sentinel pair before the remaining subjects in the cohort are dosed. Safety Review Board authorization is required before each dose escalation, and dose increments do not exceed two-fold between consecutive cohorts except where the 5 mg cohort is omitted. Each participant is observed as an inpatient for 24 hours after dosing and completes safety follow-up through Day 28.
- Conditions
- Amyotrophic Lateral Sclerosis (ALS)
- Being tested
- NI112, Placebo
- Keywords
- ALS, Amyotrophic Lateral Sclerosis, Motor Neuron Disease, NI112, Phase 1, Single Ascending Dose
- Medical subject headings
- Amyotrophic Lateral Sclerosis, Motor Neuron Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NI112Drug
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.
PlaceboDrug
Sterile normal saline (0.9% sodium chloride), administered as a single subcutaneous injection on Day 1.
| Study group | Role | What they receive |
|---|---|---|
| NI112 2.5 mg | Experimental | Drug: NI112 Injection 2.5 mg Receives: Drug: NI112 |
| NI112 5 mg | Experimental | Drug: NI112 Injection 5 mg Receives: Drug: NI112 |
| NI112 10 mg | Experimental | Drug: NI112 Injection 10 mg Receives: Drug: NI112 |
| NI112 20 mg | Experimental | Drug: NI112 Injection 20 mg Receives: Drug: NI112 |
| NI112 40 mg | Experimental | Drug: NI112 Injection 40 mg Receives: Drug: NI112 |
| NI112 80 mg | Experimental | Drug: NI112 Injection 80 mg Receives: Drug: NI112 |
| NI112 120 mg | Experimental | Drug: NI112 Injection 120 mg Receives: Drug: NI112 |
| Placebo | Placebo comparator | Drug: Placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With incidence and severity of treatment-emergent adverse events
Number and percentage of participants with treatment-emergent adverse events, graded by severity according to NCI CTCAE version 5.0.
Measured: Day 1 through Day 28
Number of Participants With incidence and severity of treatment-emergent serious adverse events
Number and percentage of participants with treatment-emergent serious adverse events, graded by severity according to NCI CTCAE version 5.0.
Measured: Day 1 through Day 28
Number of Participants With Treatment-Emergent Clinically Significant Blood Pressure Abnormalities
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.
Measured: Day 1 through Day 28
Number of Participants With Treatment-Emergent Clinically Significant Pulse Rate Abnormalities
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.
Measured: Day 1 through Day 28
Number of Participants With Treatment-Emergent Clinically Significant Respiratory Rate Abnormalities
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.
Measured: Day 1 through Day 28
Number of Participants With Treatment-Emergent Clinically Significant Body Temperature Abnormalities
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.
Measured: Day 1 through Day 28
Number of Participants With Treatment-Emergent Clinically Significant Neurological Examination Findings
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.
Measured: Day 1 through Day 8
Number of Participants With Treatment-Emergent Clinically Significant Physical Examination Findings
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.
Measured: Day 1 through Day 8
Number of Participants With Treatment-Emergent Clinically Significant 12-Lead Electrocardiogram Abnormalities, Including QT Interval Corrected by Fridericia's Formula (QTcF)
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
Measured: Day 1 through Day 28
Number of Participants With Treatment-Emergent Clinically Significant Hematology Abnormalities
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.
Measured: Day 1 through Day 28
Number of Participants With Treatment-Emergent Clinically Significant Serum Chemistry Abnormalities
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.
Measured: Day 1 through Day 28
Number of Participants With Treatment-Emergent Clinically Significant Urinalysis Abnormalities
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.
Measured: Day 1 through Day 28
Number of Participants With discontinuations due to adverse events
Number and percentage of participants discontinuing study intervention or withdrawing from the study because of an adverse event.
Measured: Day 1 through Day 28
Maximum tolerated dose of single-dose NI112
The maximum tolerated dose identified by the Safety Review Board applying the pre-specified dose-escalation and stopping criteria together with clinical judgment.
Measured: 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
Secondary outcomes (7)
Peak Plasma Concentration (Cmax) of NI112
NI112 concentration in plasma is measured by a validated analytical assay in samples collected predose on Day 1, at 1, 2, 4 and 6 hours postdose on Day 1, at 24 hours postdose on Day 2, on Day 8 and on Day 28. Cmax is the maximum observed plasma concentration, reported as a geometric mean with geometric coefficient of variation by dose cohort.
Measured: Predose and 1, 2, 4, 6 and 24 hours postdose, and on Day 8 and Day 28
Time to Peak Plasma Concentration (Tmax) of NI112
NI112 concentration in plasma is measured by a validated analytical assay in samples collected predose on Day 1, at 1, 2, 4 and 6 hours postdose on Day 1, at 24 hours postdose on Day 2, on Day 8 and on Day 28. Tmax is the time at which the maximum observed plasma concentration occurs, reported as a median with range by dose cohort.
Measured: Predose and 1, 2, 4, 6 and 24 hours postdose, and on Day 8 and Day 28
Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUC0-last) of NI112
NI112 concentration in plasma is measured by a validated analytical assay in samples collected predose on Day 1, at 1, 2, 4 and 6 hours postdose on Day 1, at 24 hours postdose on Day 2, on Day 8 and on Day 28. AUC0-last is calculated by the trapezoidal method to the last measurable concentration, reported as a geometric mean with geometric coefficient of variation by dose cohort.
Measured: Predose and 1, 2, 4, 6 and 24 hours postdose, and on Day 8 and Day 28
Area Under the Plasma Concentration Versus Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of NI112
NI112 concentration in plasma is measured by a validated analytical assay in samples collected predose on Day 1, at 1, 2, 4 and 6 hours postdose on Day 1, at 24 hours postdose on Day 2, on Day 8 and on Day 28. AUC0-inf is AUC0-last plus the extrapolated terminal area, reported as a geometric mean with geometric coefficient of variation by dose cohort, and is calculated where the terminal phase is adequately characterized.
Measured: Predose and 1, 2, 4, 6 and 24 hours postdose, and on Day 8 and Day 28
Apparent Terminal Elimination Half-Life (t1/2) of NI112 in Plasma
NI112 concentration in plasma is measured by a validated analytical assay in samples collected predose on Day 1, at 1, 2, 4 and 6 hours postdose on Day 1, at 24 hours postdose on Day 2, on Day 8 and on Day 28. t1/2 is the natural logarithm of 2 divided by the terminal elimination rate constant, reported as a geometric mean with geometric coefficient of variation by dose cohort.
Measured: Predose and 1, 2, 4, 6 and 24 hours postdose, and on Day 8 and Day 28
Cerebrospinal fluid concentration of NI112
Cerebrospinal fluid is collected by lumbar puncture predose on Day 1 and 24 hours postdose on Day 2, and NI112 concentration is measured by a validated analytical assay. The concentration is reported as a geometric mean with geometric coefficient of variation by dose cohort.
Measured: Day 1 predose and Day 2, 24 hours postdose
Cerebrospinal fluid to plasma partition coefficient
Cerebrospinal fluid is collected by lumbar puncture predose on Day 1 and 24 hours postdose on Day 2, and NI112 concentration is measured by a validated analytical assay. The partition coefficient is the NI112 concentration in cerebrospinal fluid divided by the NI112 concentration in the matched plasma sample, reported as a dimensionless ratio, geometric mean with geometric coefficient of variation by dose cohort.
Measured: Day 2, 24 hours postdose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Oct 2026
- Study start22 Jan 2027 (estimated)
- Primary completion1 Mar 2028 (estimated)
- Study completion1 Mar 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Amyotrophic Lateral Sclerosis (ALS)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sachi Bioworks Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Nathan P. Staff, M.D. Ph.D., Principal investigator, Mayo Clinic Rochester, Rochester, MN
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07906665
- Sponsor's protocol ID
- SB-ALS-101
- Status last verified
- Oct 2026
- First submitted
- 20 Oct 2026
- Last updated
- 30 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data will not be shared. This is a first-in-human study of up to 40 participants with a rare disease at three named sites, with dose level, visit dates and detailed demographic data recorded for each participant. A dataset of that size and specificity cannot be reliably de-identified, and the risk of re-identifying individual participants outweighs the value of release. Summary results will be posted on ClinicalTrials.gov.
Study at a glance
From the registry record, last updated by the sponsor on 30 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Placebo-Controlled Study of NI112 in Adults With Amyotrophic Lateral Sclerosis (ALS): Evaluation of Safety, Tolerability, and Pharmacokinetics of Single Ascending Doses
- ClinicalTrials.gov ID
- NCT07906665
- Acronym / sponsor ID
- SB-ALS-101
- Conditions
- Amyotrophic Lateral Sclerosis (ALS)
- Keywords
- ALS, Amyotrophic Lateral Sclerosis, Motor Neuron Disease, NI112, Phase 1, Single Ascending Dose
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Sachi Bioworks Inc.Industry (pharma, biotech, devices)
- Study start
- 22 Jan 2027 (estimated)
- Primary completion
- 1 Mar 2028 (estimated)
- Study completion
- 1 Mar 2028 (estimated)
- First posted
- 30 Oct 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a Phase 1, first-in-human, multi-center, randomized, double-blind, placebo-controlled, sequential single ascending dose-escalation study evaluating the safety, tolerability and pharmacokinetics of NI112 administered by subcutaneous injection to adults with amyotrophic lateral sclerosis. Up to seven sequential dose cohorts are planned at 2.5, 5, 10, 20, 40, 80 and 120 mg. Cohorts at 20 mg and below enroll 4 subjects randomized 3 active to 1 placebo; cohorts above 20 mg enroll 8 subjects randomized 6 active to 2 placebo. The 5 mg cohort may be omitted only under pre-specified pharmacokinetic criteria. The Safety Review Board may expand any of the first four cohorts to a maximum of 8 subjects, and total enrollment will not exceed 40 subjects. Within each new dose level the first two subjects, one active and one placebo, are dosed at least 48 hours apart and the Safety Review Board reviews all available safety data for that sentinel pair before the remaining subjects in the cohort are dosed. Safety Review Board authorization is required before each dose escalation, and dose increments do not exceed two-fold between consecutive cohorts except where the 5 mg cohort is omitted. Each participant is observed as an inpatient for 24 hours after dosing and completes safety follow-up through Day 28.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| NI112 2.5 mg | Experimental | Drug: NI112Drug: NI112 Injection 2.5 mg |
| NI112 5 mg | Experimental | Drug: NI112Drug: NI112 Injection 5 mg |
| NI112 10 mg | Experimental | Drug: NI112Drug: NI112 Injection 10 mg |
| NI112 20 mg | Experimental | Drug: NI112Drug: NI112 Injection 20 mg |
| NI112 40 mg | Experimental | Drug: NI112Drug: NI112 Injection 40 mg |
| NI112 80 mg | Experimental | Drug: NI112Drug: NI112 Injection 80 mg |
| NI112 120 mg | Experimental | Drug: NI112Drug: NI112 Injection 120 mg |
| Placebo | Placebo comparator | Drug: PlaceboDrug: Placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- • 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.
Key exclusion criteria (23 listed)
- • Positive test for, or history of, human immunodeficiency virus.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NI112Antisense 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. | Drug | NI112 10 mg, NI112 120 mg, NI112 2.5 mg, NI112 20 mg, NI112 40 mg, NI112 5 mg, NI112 80 mg |
| PlaceboSterile normal saline (0.9% sodium chloride), administered as a single subcutaneous injection on Day 1. | Drug | Placebo |
Primary outcome
Number of Participants With incidence and severity of treatment-emergent adverse events
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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)
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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.
7 secondary outcomes
Peak Plasma Concentration (Cmax) of NI112
Time frame: Predose and 1, 2, 4, 6 and 24 hours postdose, and on Day 8 and Day 28
Time to Peak Plasma Concentration (Tmax) of NI112
Time frame: Predose and 1, 2, 4, 6 and 24 hours postdose, and on Day 8 and Day 28
Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUC0-last) of NI112
Time frame: Predose and 1, 2, 4, 6 and 24 hours postdose, and on Day 8 and Day 28
Area Under the Plasma Concentration Versus Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of NI112
Time frame: Predose and 1, 2, 4, 6 and 24 hours postdose, and on Day 8 and Day 28
Apparent Terminal Elimination Half-Life (t1/2) of NI112 in Plasma
Time frame: Predose and 1, 2, 4, 6 and 24 hours postdose, and on Day 8 and Day 28
Cerebrospinal fluid concentration of NI112
Time frame: Day 1 predose and Day 2, 24 hours postdose
Cerebrospinal fluid to plasma partition coefficient
Time frame: Day 2, 24 hours postdose
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Oct 2026.
- Individual participant dataSharing planned: No. Individual participant data will not be shared. This is a first-in-human study of up to 40 participants with a rare disease at three named sites, with dose level, visit dates and detailed demographic data recorded for each participant. A dataset of that size and specificity cannot be reliably de-identified, and the risk of re-identifying individual participants outweighs the value of release. Summary results will be posted on ClinicalTrials.gov.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Nathan P. Staff, M.D. Ph.D. principal investigator
Mayo Clinic Rochester, Rochester, MN
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing NI112 in people with Amyotrophic Lateral Sclerosis (ALS), run by Sachi Bioworks Inc. at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 30 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Prashant Nagpal, Ph.D. (7203612159, nagpal@sachibio.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With incidence and severity of treatment-emergent adverse events (time frame: Day 1 through Day 28). The study lists 14 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Oct 2026.