CTRI/2023/10/058660 [Registered on: 13/10/2023] Trial Registered Prospectively
Last Modified On:
13/12/2024
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Randomized, Parallel Group, Multiple Arm Trial
Public Title of Study
A study to evaluate Safety,Efficacy,Tolerability, Pharmacokinetics, and Pharmacodynamics of ZYIL1 in patients with Amyotrophic Lateral Sclerosis
Scientific Title of Study
A phase 2, proof-of-concept, placebo controlled, randomized, multi-centre, double blind study of ZYIL1 to evaluate the efficacy, safety, tolerability, pharmacokinetics and pharmacodynamics in patients with Amyotrophic Lateral Sclerosis (ALS)
Trial Acronym
NIL
Secondary IDs if Any
Secondary ID
Identifier
ZYIL.23.003 Ver 01 Dated 27 May 2023
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Route :- Oral
Strength : 25 and 50 mg Duration : 56 days
Intervention
ZYIL1 Capsules
Route :- Oral
Strength : 25 and 50 mg
Duration : 56 days
Inclusion Criteria
Age From
18.00 Year(s)
Age To
80.00 Year(s)
Gender
Both
Details
1.Male and/or female patients aged between 18 and 80 years (inclusive at screening).
2. Diagnosis of probable or definite ALS, according to the revised version of the El Escorial
World Federation of Neurology criteria. Refer Appendix III - El Escorial Criteria.
3. Time since onset# of first symptom of ALS ≤9 months
4. Slow Vital Capacity (SVC) ≥ 50% of the predicted value
5. Be able to swallow the study capsules during study
6. Either not currently receiving riluzole or on a stable dose of riluzole for at least 4 weeks
before the screening visit. Participants receiving riluzole are expected to remain on the
same dose throughout the duration of the study
7. Either not currently receiving edaravone or on edaravone treatment. Participants
receiving edaravone must have completed at least 1 cycle of treatment before the
screening visit and are expected to continue with stable dose edaravone treatment
throughout the duration of the study
ExclusionCriteria
Details
1)With significant cognitive impairment, psychiatric disease, other neurodegenerative
disorder (e.g., Parkinson disease or AD), substance abuse other causes of neuromuscular weakness, or any other condition that would make the participants unsuitable for
participating in the study or could interfere with assessment or completing the study in
the opinion of the Investigator
2. History of recent serious infection (e.g., pneumonia, septicemia) within 4 weeks of the
screening visit; infection requiring hospitalization or treatment with IV antibiotics,
antivirals, or antifungals within 4 weeks of screening; or chronic bacterial infection (such
as tuberculosis) deemed unacceptable as per the Investigator’s judgment
3. With active herpes zoster infection within 2 months prior to the screening visit
4. A documented history of attempted suicide within 6 months prior to the screening visit,
or in the Investigator’s judgment are at risk for a suicide attempt
5. History of unstable or severe cardiac, pulmonary, oncological, hepatic, or renal disease
or another medically significant illness other than ALS precluding their safe
participation in this study
6. Participants who are pregnant or are currently breastfeeding
7. A known history of allergy to any ingredients of ZYIL1
8. Patients taking concomitant medicines within 7 days or 5 half-lives of the medication
(whichever is longer) prior to first dose of study drug administration till end of the study,
which are substrate of CYP1A2 enzymes (e.g., alosetron, caffeine, duloxetine,
melatonin, ramelteon, tasimelteon, tizanidine etc.) and CYP2B6 enzymes (e.g.,
bupropion, efavirenz etc.).
9. Use of any steroids, colchicine or anti-IL-1 inhibitors within 7 days or 5 half-lives of the
medication (whichever is longer) prior to first dose of study drug administration.
10. Use of any investigational drugs concurrently or within 4 weeks or 5 half-lives
(whichever is longer), prior to first dose of study drug administration.
11. Any clinically significant and/or laboratory significant value or other instability that
would prevent the patient from participating in the study as determined by the
Investigator.
12. Received a live vaccine within 14 days before the screening visit or planning to receive
during the study
13. Participants who have received stem cell or gene therapy for ALS at any time in the past
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
On-site computer system
Blinding/Masking
Participant and Investigator Blinded
Primary Outcome
Outcome
TimePoints
To measure the efficacy of the treatment using the slope of progression with the revised
Amyotrophic Lateral Sclerosis Functional Rating Scale
Baseline to Day 84
Secondary Outcome
Outcome
TimePoints
safety & tolerability of ZYIL1 in patients with ALS
Baseline to Day 84
evaluate pharmacokinetics of ZYIL1
Baseline to Day 84
evaluate effect of ZYIL1 on neurofilament biomarker
Baseline to Day 84
Target Sample Size
Total Sample Size="24" Sample Size from India="24" Final Enrollment numbers achieved (Total)= "24" Final Enrollment numbers achieved (India)="24"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
ZYIL1 is expected to show benefit in patients with Amyotrophic Lateral Sclerosis (ALS). The present study aims to determine the safety, tolerability, pharmacokinetics, and pharmacodynamics of ZYIL1 when administered to subjects with ALS.
This is a proof-of-concept, placebo controlled, randomized, double blind study designed to evaluate the efficacy, safety, tolerability, pharmacokinetics, and pharmacodynamics in patients with Amyotrophic Lateral Sclerosis following a twice daily oral administration of ZYIL1 or matching placebo. Twenty-four (24) patients will be randomly assigned in a 1:1:1:1 ratio to oral twice daily capsules of ZYIL1 25 mg or ZYIL1 50 mg or ZYIL1 75 mg or matching placebo. Patients on ZYIL1 25 mg and 50 mg arm along with matching placebo will be randomized first. Treatment duration will be twelve (12) weeks.