Phase 2 Study for SAR443820 in Participants With Amyotrophic Lateral Sclerosis (ALS) (HIMALAYA)
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| ClinicalTrials.gov Identifier: NCT05237284 |
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Recruitment Status :
Recruiting
First Posted : February 14, 2022
Last Update Posted : May 3, 2023
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This is a parallel treatment, Phase 2, randomized, double-blind study to assess the efficacy, safety, tolerability, PK, and PD of twice daily (BID) oral SAR443820 compared with placebo in male and female participants,18 to 80 years of age with ALS followed by an open label, longterm extension period.
Study ACT16970 consists of 2 parts (A and B) as follows:
Part A is a 24week, double blind, placebo controlled part, preceded by a screening period of up to 4 weeks before Day 1.
On Day 1 of Part A, participants will be randomized in a 2:1 ratio to the SAR443820 treatment arm or matching placebo arm as listed below:
Treatment arm: SAR443820, BID
Placebo arm: Placebo, BID
Randomization will be stratified by the geographic region of the study site, region of ALS onset (bulbar vs other areas), use of riluzole (yes vs no), use of edaravone (yes vs no) and use of the combination of sodium phenylbutyrate and taurursodiol (named Relyvrio in the United States of America [USA] and Albrioza in Canada) (yes vs no). Participants will attend in clinic study assessments at baseline (Day 1), Week 2, Week 4, Week 8, Week 16, and Week 24, and will receive a phone call at Week 12 and Week 20. All ongoing participants in Part A will rollover to part B. The Week 24 Visit is the end of Part A and the beginning of Part B.
Part B is an open label, longterm extension period that starts from the end of Part A (Week 24) and continues up to Week 106. The objectives of Part B are to further determine the safety and efficacy of longterm SAR443820 treatment. The treatment assignment of participants in Part A will remain blinded to Investigators, participants, and site personnel until the end of Part B. Every participant, except those who discontinued Investigational Medicinal Product (IMP) treatment permanently in Part A , will receive BID oral tablets of SAR443820 in Part B.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Amyotrophic Lateral Sclerosis | Drug: SAR443820 Drug: Placebo | Phase 2 |
Part A of the study will last for 24 weeks, and participants will receive BID oral SAR443820 or placebo in a double-blind fashion for 24 weeks. All ongoing participants in Part A will rollover to Part B.
Part B begins at the end of Week 24 and continues up to Week 106. All participants except those who discontinued Investigational Medicinal Product (IMP) treatment permanently in Part A will receive BID oral tablets of SAR443820 in Part B.
The study duration includes an up to 4-week screening period, 24-week double blind treatment period in Part A, 80-week open label treatment period in Part B, and 2-week post treatment follow up period, with a maximum total study duration of 110 weeks.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 261 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Triple (Participant, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of SAR443820 in Adult Participants With Amyotrophic Lateral Sclerosis, Followed by an Open-label Extension |
| Actual Study Start Date : | April 13, 2022 |
| Estimated Primary Completion Date : | February 2, 2024 |
| Estimated Study Completion Date : | August 12, 2025 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: SAR443820
twice daily (BID) oral SAR443820
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Drug: SAR443820
Tablet oral |
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Placebo Comparator: Placebo
twice daily (BID) oral placebo
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Drug: Placebo
Tablet |
- Change from baseline in the ALSFRS-R total score -Part A [ Time Frame: From baseline to Week 24 ]
- Combined assessment of the function and survival (CAFS) score -Part B [ Time Frame: Week 52 ]
- Combined assessment of the function and survival (CAFS) score -Part A [ Time Frame: Week 24 ]
- Change from baseline in slow vital capacity (SVC) -Part A [ Time Frame: From baseline to Week 24 ]
- Muscle Strength - Part A [ Time Frame: From baseline to Week 24 ]Measured using a grip dynamometer and a handheld dynamometer (HHD)
- Change from baseline in Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ5) -Part A [ Time Frame: From baseline to Week 24 ]
- Change from baseline in serum neurofilament light chain (NfL) -Part A [ Time Frame: From baseline to Week 24 ]
- Number of patients with treatment emergent adverse events (TEAE) and Serious adverse event (SAE) - Part A [ Time Frame: Up to Week 24 ]
- Assessment of pharmacokinetic parameter -Plasma concentration of SAR443820 -Part A [ Time Frame: Day 1, Week 2, Week 8 ]
- Combined assessment of the function and survival (CAFS) score - Part B [ Time Frame: Week 76, Week 104 ]
- Change from baseline in the ALSFRS R total score-Part B [ Time Frame: From baseline to Week 52 and Week 76 and Week 104 ]
- Time from baseline to the occurrence of either death, or permanent assisted ventilation (>22 hours daily for >7 consecutive days), whichever comes first - Part B [ Time Frame: Up to Week 106 ]
- Time from baseline to the occurrence of death-Part B [ Time Frame: Up to Week 106 ]
- Change from baseline in slow vital capacity (SVC)-Part B [ Time Frame: From baseline to Week 52, Week 76 and Week 104 ]
- Change from baseline in Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-5)-Part B [ Time Frame: From baseline to Week 52, Week 76 and Week 104 ]
- Change from baseline in serum neurofilament light chain (NfL)-Part B [ Time Frame: Week 52 ]
- Number of patients with treatment emergent adverse events (TEAE) and Serious adverse event (SAE) -Part B [ Time Frame: Up to Week 106 ]
- Assessment of pharmacokinetic parameter Plasma concentration of SAR443820 -Part B [ Time Frame: Week 28 ]
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years to 80 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Diagnosis of possible, clinically probable ALS, clinically probable laboratory supported ALS, or clinically definite ALS according to the revised version of the El Escorial World Federation of Neurology criteria
- Time since onset of first symptom of ALS ≤2 years.
- Slow Vital Capacity (SVC) ≥60% of the predicted value.
- Be able to swallow the study tablets at the screening visit.
- 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.
- Either not currently receiving edaravone or on the approved standard schedule of edaravone treatment. Participants receiving edaravone must have completed at least 1 cycle of treatment before the screening visit and are expected to continue edaravone treatment throughout the duration of the study.
- Either not currently receiving the combination of sodium phenylbutyrate and taurursodiol or on the approved standard schedule of the combination of sodium phenylbutyrate and taurursodiol treatment for at least 4 weeks before the screening visit. Participants receiving the combination of sodium phenylbutyrate and taurursodiol are expected to remain on the approved standard schedule throughout the duration of the study.
- Participants with a body weight no less than 45 kg and body mass index no less than 18 kg/m2 at the screening visit
- Female participants with childbearing potential are eligible to participate if they are not pregnant or breastfeeding and agree to use adequate contraceptive method during study intervention period and for at least 32 days after the last dose of study drug.
- Male participants must agree to use highly effective contraceptive method during the study period and for at least 92 days following their last dose of the study drug. Male participants must not donate sperms for the duration of study and 92 days after last dose of study drug.
Exclusion Criteria:
- A history of seizure (History of febrile seizure during childhood is allowed).
- Having central IV lines, such as a peripherally inserted central catheter (PICC XE ' PICC ' \f Abbreviation \t 'peripherally inserted central catheter' ) or midline or portacath lines.
- With significant cognitive impairment, psychiatric disease, other neurodegenerative disorder (eg, 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.
- History of recent serious infection (eg, 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.
- With active herpes zoster infection within 2 months prior to the screening visit.
- A documented history of attempted suicide within 6 months prior to the screening visit, present with suicidal ideation of category 4 or 5 on the Columbia Suicide Severity Rating Scale (CSSRS) , or in the Investigator's judgment are at risk for a suicide attempt.
- 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.
- Participants who are pregnant or are currently breastfeeding.
- A known history of allergy to any ingredients of SAR443820.
- Currently or previously treated with any strong or moderate CYP3A4 inhibitors or strong CYP3A4 inducers listed in Appendix 10 of the protocol within the specified washout period before the screening visit.
- Received a live vaccine within 14 days before the screening visit.
- Participants with concurrent participation in any other interventional clinical study or who have received treatment with another investigational drug (eg sodium phenylbutyrate or taurursodiol ) within 4 weeks or 5 halflives of the investigational agent before the screening visit, whichever is longer.
- Participants who have received stem cell or gene therapy for ALS at any time in the past.
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3.0 × upper limit of normal (ULN)
- Bilirubin >1.5 × ULN unless the participant has documented Gilbert syndrome (isolated bilirubin >1.5 × ULN is acceptable if bilirubin is fractionated and direct bilirubin is <35%)
- Serum albumin <3.5 g/dL
- Estimated glomerular filtration rate <60 mL/min/1.73 m2 (Modification of Diet in Renal Disease [MDRD])
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05237284
| Contact: Trial Transparency email recommended (Toll free for US & Canada) | 800-633-1610 ext option 6 | Contact-US@sanofi.com |
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| Study Director: | Clinical Sciences & Operations | Sanofi |
| Responsible Party: | Sanofi |
| ClinicalTrials.gov Identifier: | NCT05237284 |
| Other Study ID Numbers: |
ACT16970 U1111-1263-5766 ( Registry Identifier: ICTRP ) 2021-004156-42 ( EudraCT Number ) |
| First Posted: | February 14, 2022 Key Record Dates |
| Last Update Posted: | May 3, 2023 |
| Last Verified: | May 2, 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
| Product Manufactured in and Exported from the U.S.: | No |
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Motor Neuron Disease Amyotrophic Lateral Sclerosis Sclerosis Pathologic Processes Neurodegenerative Diseases Nervous System Diseases |
Neuromuscular Diseases Spinal Cord Diseases Central Nervous System Diseases TDP-43 Proteinopathies Proteostasis Deficiencies Metabolic Diseases |