E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10070668 |
E.1.2 | Term | Huntington's disease |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the safety and tolerability of long-term exposure to WVE-120101 in patients with early manifest Huntington’s disease (HD) |
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E.2.2 | Secondary objectives of the trial |
To evaluate the clinical and pharmacodynamic (PD) effects of WVE-120101 in patients with early manifest HD |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patient has documented ability to understand the written study informed consent forms (ICFs) at the time of screening and has provided signed written informed consent prior to any study procedures. 2. Patient successfully completed their Day 168 or 196 visit (depending upon dosing cohort and requiremens in a given country) of the Phase 1b/2a study with WVE-120101, WVE-HDSNP1001. 3. In the opinion of the Investigator, the patient is able to tolerate all study procedures, is willing to comply with all other protocol requirements, and tolerated study drug in the parent study. 4. Patient is willing to practice highly effective contraception for the duration of the study if the patient or their partner are of childbearing potential. Non-childbearing potential and highly effective methods of contraception are defined in the protocol.
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E.4 | Principal exclusion criteria |
1. Clinically significant medical finding on the physical examination other than HD that, in the judgment of the Investigator, will make the patient unsuitable for participation in and/or completion of the study procedures. 2. Received an investigational drug other than WVE-120101, including an investigational oligonucleotide, within the past 1 year or 5 half-lives of the drug, whichever is longer. 3. Implantable central nervous system (CNS) device that may interfere with ability to administer study drug via lumbar puncture or undergo brain magnetic resonance imaging (MRI) scan. 4. Diagnostic and Statistical Manual of Mental Disorders 5th Edition (DSM-5) diagnosis at the Screening Visit of active alcohol, cannabinoid, or other substance use disorder (except nicotine). 5. Positive for opioids (unprescribed), cocaine, amphetamines, methadone, barbiturates, methamphetamine, or phencyclidine at the Screening Visit. 6. Pregnant (as determined by a serum pregnancy test) or breast feeding at the Screening Visit, or plans to become pregnant during the course of the study. 7. Clinically significant laboratory abnormality at Screening, including, but not limited to: a. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) values at Screening or Baseline >3 times the upper limit of normal (ULN). b. Renal insufficiency, defined as either serum creatinine >1.8 mg/dL or creatinine clearance <40 mL/min. 8. Clinically significant abnormality at Screening electrocardiogram (ECG), including but not limited to a confirmed QT interval corrected for heart rate (QTc) ≥450 msec for males or ≥470 msec for females. 9. Clinically significant cardiovascular, endocrine, hepatic, renal, pulmonary, gastrointestinal, neurologic, malignant, metabolic, psychiatric, or other condition that, in the opinion of the Investigator, precludes the patient’s safe participation in the study or would interfere with the study assessments. 10. Bone, spine, bleeding, or other disorder that exposes the patient to risk of injury or unsuccessful lumbar puncture. 11. Inability to undergo brain MRI (with or without sedation). 12. In the opinion of the Investigator, deemed to be at significant risk for suicidal behavior. 13. Involved directly or indirectly in the conduct and administration of this study as an Investigator, subinvestigator, study coordinator, or other study staff member, or the patient is a first-degree family member, significant other, or relative residing with one of the above persons involved directly or indirectly in the study. 14. Anticipates using antiplatelet or anticoagulant therapy during the course of the study. Patients who received antiplatelet or anticoagulant therapy must complete one of the following washout periods before the Screening Visit: a. A 7-day washout period for antiplatelet therapy, b. A 1-day washout period for anticoagulants (except warfarin), or c. A 5-day washout period for warfarin. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The number of patients with adverse events (AEs), severity of AEs, number of patients with serious AEs (SAEs), clinically significant changes in laboratory values, and the number of patients who withdraw due to AEs |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Every 4 weeks from week 1 to week 97. |
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E.5.2 | Secondary end point(s) |
Clinical Effects Endpoint(s): • Change from baseline in the Total Functional Capacity (TFC), administered as part of the Unified Huntington’s Disease Rating Scale (UHDRS) • Change from baseline in the motor, cognitive, independence, and functional assessments administered as part of the UHDRS • Change from baseline in the composite UHDRS (cUHDRS) • Change from baseline in the Short Problem Behaviors Assessment (PBA-s)
Pharmacodynamic Endpoints: • Change from baseline in the concentration of mutant huntingtin (mHTT) protein in CSF • Changes from baseline MRI of the brain • Change from baseline in exploratory biomarkers, including but not limited to neurofilament light (NFL)
PK Endpoints: • PK parameters of WVE-120101 in plasma • WVE-120101 and WVE-120101-related metabolite excretions in urine • Concentration of WVE-120101 in CSF |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Every 12 weeks from week 1 to week 97. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Canada |
Denmark |
France |
Germany |
Poland |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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LPLV (including follow-up visit) |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 8 |