A clinical study to learn whether a new drug, TPN-101, is safe when given to patients with amyotrophic lateral sclerosis or frontotemporal dementia due to a genetic mutation called C9orf72 hexanucleotide repeat expansion.

Phase 1

• Conditions: Amyotrophic lateral sclerosis or frontotemporal dementia due to a genetic mutation called C9orf72 hexanucleotide repeat expansion; MedDRA version: 21.1Level: PTClassification code 10002026Term: Amyotrophic lateral sclerosisSystem Organ Class: 10029205 - Nervous system disorders; MedDRA version: 21.1Level: PTClassification code 10068968Term: Frontotemporal dementiaSystem Organ Class: 10029205 - Nervous system disorders; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: EUCTR2021-002251-11-DE
• Lead Sponsor: Transposon Therapeutics, Inc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-08-02
• Last Update Posted: 15 January 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

1. Males or females = 18 years of age at the time of informed consent
2. Have documentation of a clinical genetic test demonstrating the presence of a confirmed hexanucleotide repeat expansion (HRE) in the C9orf72 gene from a laboratory using an assay that has the relevant mark of conformity (United Kingdom Conformity Assessed [UKCA], Conformitè Europëenne [CE], or CE United Kingdom Northern Ireland [UKNI]) or Clinical Laboratory Improvement Amendments (CLIA) certification in the United States (Note: The HRE in the C9orf72 gene is present in about 10-15% of patients with ALS or FTD. Therefore, confirmation of this mutation should be part of the pre-screening for inclusion in the study. Patients who are not already known to have this mutation should not be screened for inclusion, i.e., genetic testing for this mutation is not a part of the study procedures.)
3. If female, must be postmenopausal (for at least 2 years), surgically sterilized (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy), or agree to use highly effective methods of contraception, e.g., combined (estrogen and progestogen containing) or progestogen-only hormonal
contraception associated with inhibition of ovulation; intrauterine device (IUD); intrauterine hormone-releasing system (IUS); bilateral tubal occlusion; vasectomized partner (provided that the partner is the sole sexual partner of the women of child-bearing potential [WOCBP] trial participant and that the vasectomized partner has received medical assessment of the surgical success); or sexual abstinence (defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments), from Screening through 3 months after the last dose of the study medication
4. If male, with a partner who is not postmenopausal (for at least 2 years) or surgically sterilized (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy), the patient must agree that he and his partner will use highly effective methods of contraception, e.g., combined (estrogen and progestogen containing) or progestogen-only hormonal contraception associated with inhibition of ovulation; IUD; IUS; bilateral tubal occlusion; vasectomy (provided that he has received medical assessment of the surgical success); or sexual abstinence (defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments), from Screening through 3 months after the last dose of the study
medication
5. Able to perform all protocol-specified assessments, including neuropsychological tests; and comply with taking study medication and the study visit schedule, as judged by the investigator
6. Have a reliable caregiver/informant to accompany the patient to all study visits. Caregiver/informant must be able to read, understand, and
speak local language fluently to ensure comprehension of informed consent and informant-based assessments of the patient. Caregiver/informant must also have frequent contact with patient (at least 3 hours per week at one time or at different times) and be willing to monitor the patient's health and concomitant medications throughout the study
7. Able to understand and provide written informed consent at Screening, or has a legally authorized representation (LAR) who can provide such consent
8. Patient or LAR agree to allow data sharing across observational longitudinal and interventional studies using an encrypted global unique iden

Exclusion Criteria

1. Presence of other significant neurological or psychiatric disorders
including, but not limited to, biomarker confirmed Alzheimer's disease;
dementia with Lewy bodies; prion disease; progressive supranuclear
palsy; Parkinson's disease; multiple sclerosis; other causes of
neuromuscular weakness; a
primary or severe psychotic disorder; severe bipolar or unipolar
depression
2. Prior history of suicidal thoughts or behavior that are believed to
represent a current safety risk, or a Yes response to Questions 4 or 5
on the Columbia Suicide Severity Rating Scale (C-SSRS) at Screening
3. History of clinically significant brain abnormality, including, but not
limited to, stroke due to hemorrhage or infarction; cerebral contusion;
encephalomalacia; aneurysm; vascular malformation (angiomas or other
benign vascular malformations that are judged by the investigator to be
stable and not clinically significant are not exclusionary); hydrocephalus;
epilepsy; space-occupying lesion (e.g., abscess or brain tumor); severe
head injury within the past 20 years; symptoms or signs of elevated
intracranial pressure (e.g., symptoms or history of head injury or
abnormal funduscopic exam). If there is history or evidence on
neurologic exam suggesting possible subdural hematoma (SDH),
patients should be fully evaluated, including magnetic resonance
imaging (MRI) if indicated, to exclude significant, new SDH
4. Active alcohol, drug, or substance abuse/dependence, or any other
reason that makes it unlikely that the patient will comply with study
procedures in the opinion of the investigator
5. Clinically significant intercurrent illness or medical condition (e.g.,
hematological, endocrine, cardiovascular, renal, hepatic, or
gastrointestinal disease) that would jeopardize the safety of the patient,
limit participation, or compromise the interpretation of the data derived
from the patient
6. Tracheostomy or diaphragmatic pacing
7. Autoimmune disease requiring treatment or management (quiescent
rheumatoid arthritis, psoriasis, or controlled Type 1 diabetes are
acceptable)
8. History of human immunodeficiency virus (HIV), hepatitis B, or any
active infection during Screening, unless the patient will have been
symptom-free for at least 30 days prior to randomization. Treated
hepatitis C with no laboratory evidence of active disease and liver
enzymes <2 × upper limit of normal (ULN) is allowed
9. History of cancer within 5 years of Screening, with the exception of
fully treated non-melanoma skin cancers
10. Receipt of an investigational agent within 30 days or 5 half-lives
prior to Screening, whichever is longer
11. Treatment with an immunomodulator within 6 months of Screening
12. Receipt of systemic corticosteroids within 30 days prior to Screening
13. Any vaccination within 30 days prior to randomization
14. Hypertension, defined as confirmed systolic blood pressure (SBP) >
170 mmHg and/or diastolic blood pressure (DBP) > 100 mmHg at Screening
15. Hypotension, defined as confirmed SBP < 90 mmHg and/or DBP < 60
mmHg at Screening
16. Any major surgery within 4 weeks of Screening or a planned major
surgery during the trial
17. Females who are pregnant (positive pregnancy test at Screening or
prior to administration of study drug) or breastfeeding
18. Contraindication to undergoing a lumbar puncture (LP) including, but
not limited to: inability to tolerate an appropriately flexed position for
the time necessary to perform an LP; international normalized ratio
(INR) >

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the safety and tolerability of TPN-101 in patients with C9ORF72 ALS/FTD;Secondary Objective: • To assess the concentrations of TPN-101 in plasma and cerebrospinal fluid (CSF)<br>• To assess target engagement of TPN-101 in blood<br>• To assess disease-related biomarkers<br>• To assess the PD effects of TPN-101 in blood and CSF<br>• To assess inflammatory biomarkers in blood and/or CSF<br>• To assess clinical and functional status<br>• To assess survival;Primary end point(s): Incidence and severity of treatment-emergent adverse event (TEAEs) of TPN-101 administered for up to 48 weeks in patients with C9ORF72 ALS/FTD;Timepoint(s) of evaluation of this end point: 48 weeks