Amyotrophic Lateral Sclerosis (ALS) MedDRA version: 21.1 Level: PT Classification code 10002026 Term: Amyotrophic lateral sclerosis System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Product Name: AP-101
Product Code: AP-101
Pharmaceutical Form: Injection
INN or Proposed INN: Not yet available
Current Sponsor code: AP-101
Other descriptive name: Anti-(misfolded human superoxide di
Sponsors
AL-S Pharma, AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male and female participants. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. a. Male participants who agree to use highly effective/effective methods of contraception may participate in this trial: i. All men should refrain from sperm donation for the duration of the study and for 6 months after the final administered dose of AP-101 ii. Male participants with partners of childbearing potential must either remain abstinent (if this is their preferred and usual lifestyle), or must use condoms during intercourse for the duration of the study, and for 6 months after the final administered dose iii. Male participants who are in exclusively same sex relationships are not required to use contraception. b. Male participants must adhere to the contraception restrictions specified in Section 10.6 of the Protocol. c. Female participants of childbearing potential must adhere to contraception restrictions specified in Section 10.6 of the Protocol. Female participants should refrain from egg donation for the duration of the study and for 6 months following the final administered dose of AP101. d. Female participants are considered women not of child bearing potential if i. they have a congenital anomaly such as Mullerian agenesis, ii. they are infertile due to surgical sterilization, or iii. they are post- menopausal (as defined in protocol). 2. Aged 18 years or over. 3. Have possible, clinically probable, clinically probable-laboratory supported or definite familial or sporadic ALS in accordance with the El-Escorial criteria (Appendix 9, Section 10.9 of the Protocol) or who have a diagnosis of ALS as defined by the Gold Coast Criteria; progressive motor impairment documented by history or repeated clinical examination, preceded by normal motor development, and presence of upper and lower motor neuron dysfunction in at least 1 body region or lower motor neuron dysfunction in at least 2 body regions and investigations excluding other conditions. 4. In familial ALS patients, a confirmed pathogenic SOD1 mutation. 5. Onset of symptoms i.e., weakness within past 24 months prior to screening, at the time of obtaining informed consent. 6. Have SVC of =50% of predicted values. Participants with SVC of 4 hours for symptoms attributable to ALS. Use of a CPAP for pre-existing conditions will be allowed. 8. If on riluzole, must be on a stable dose for at least 30 days prior to baseline (randomization) and remain on a stable dose throughout the study. Riluzole cannot be initiated during the double blind phase of the study. Riluzole can be initiated during the OLE after Week 3 if needed based on the opinion of the investigator and the dose may be adjusted as appropriate. 9. If on edaravone, must have completed 2 cycles at baseline (randomization) and are expected to remain on the same dose throughout the study. Edaravone cannot be initiated once the participant is randomized and for the duration of the double blind phase of the study. Edaravone can be initiated during the OLE after Week 3 if needed based on the opinion of the investigator and the dose may be adjusted as appropriate. 10. If on sodium p
Exclusion criteria
Exclusion criteria: 1. Are investigator or site personnel affiliated with this study, or the immediate family of any of these. Immediate family is defined as a spouse, parent, child or sibling, whether biological or legally adopted. 2. Are participating in, or have participated in another clinical trial (or have taken an experimental therapy within the context of a clinical trial) within 5 half-lives of baseline (Day 1). 3. Have undergone a tracheostomy for ALS symptoms. 4. Are on nasal intermittent positive pressure ventilation (NIPPV) >4 hours per day for the treatment of ALS related symptoms. 5. Have other causes of neuromuscular weakness. 6. Have severe active psychiatric illness. 7. Have a diagnosis of another neurodegenerative disease (e.g. Parkinson disease, Alzheimer’s disease). 8. Have a significant pulmonary disorder not attributed to ALS or who require treatments that might complicate the evaluation of the effect of ALS on respiratory function. 9. Have cognitive impairment, severe disease in the renal, cardiovascular or hematological system. 10. Pregnant or nursing women. 11. Have been exposed to any antisense treatment targeting SOD1, including tofersen, within 6 months of the baseline visit or have known allergies or reactions to AP-101 or any of its excipients. 12. Have undergone stem cell therapy. 13. In the opinion of the investigator or sponsor, are unsuitable for inclusion in the study for any reason.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Double-blind Phase • To determine the safety and tolerability of AP-101 after multiple intravenous (IV) doses over 6 months of treatment Open-label Extension • To determine the safety and tolerability of AP-101 after multiple IV termine the safety and tolerability of AP-101 after multiple IV;Secondary Objective: Double-blind Phase • To determine the Pharmacokinetic (PK) profile of AP-101 after multiple IV dose administrations • To determine cerebrospinal fluid (CSF) penetration of AP-101 after multiple IV dosing • To determine effects of AP-101 on phospho-neurofilament heavy chain (pNfH) and neurofilament light chain (NfL) levels in CSF and plasma after multiple IV doses of AP-101 Open-label Extension • To determine the PK profile of AP 101 after multiple IV dose administrations • To determine effects of AP-101 on pNfH and NfL levels in CSF and plasma after multiple IV doses of AP 101;Primary end point(s): Double-blind Phase • Incidence of AEs and SAEs including immunogenicity. • Incidence of abnormalities in vital signs, clinical laboratory assessments, physical and neurological examinations, electrocardiograms and changes in weight. Open-label Extension • Incidence of AEs and SAEs including immunogenicity • Incidence of abnormalities in vital signs, clinical laboratory assessments, physical and neurological examinations, electrocardiograms and changes in weight;Timepoint(s) of evaluation of this end point: Double-blind Phase • AEs and SAEs from screening through 16 weeks post last dose or early termination • Immunogenicity from baseline through 16 weeks post last dose or early termination • Vital signs, laboratory measurements, electrocardiograms, changes in weight from screening through 16 weeks post last dose or early termination (excluding phone call) • Physical and neurological exam: screening, baseline, Dose 2, W3, W12, W24, 21 days - 16 weeks post last dose or early termination (excluding phone call) Open-label Extension • AEs | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Double-blind Phase • The primary PK parameters are AUC, concentration at the end of infusion and t1/2 • AP-101 levels in the CSF • Measurement of pNfH and NfL levels in the CSF and plasma after multiple IV doses of AP-101 Open-label Extension • The primary PK parameters are AUC, concentration at end of infusion and t1/2 • Measurement of pNfH and NfL levels in CSF and plasma after multiple IV doses of AP-101;Timepoint(s) of evaluation of this end point: Double-blind Phase • PK sampling from baseline through 16 weeks post last dose or early termination (excluding phone call) • CSF samples at baseline, W12, W24 and 16 weeks post last dose or early termination Open-label Extension • PK sampling at baseline, Dose 2 and 21 days - 16 weeks post last dose or early termination | — |
Countries
Belgium, Canada, Germany, Korea, Republic of, Sweden, United States
Contacts
Public ContactChorus Group
Eli Lilly and Company
Outcome results
None listed