Overview
Sponsor-declared trial summary
Phase
Phase I and Phase II (Integrated) - First administration to humans
Status
Ongoing, recruiting
Participants planned
12
Countries
1
Sites
1
Duchenne muscular dystrophy
Phase 1: Evaluate the safety and tolerability of SQY51 in DMD (Duchenne Muscular Dystrophy) patients. Phase 2a: Evaluate the safety and tolerance of SQY51 in DMD patients following 49-weeks multiple dosing. PART III - EXTENSION PHASE : Primary and secondary objectives and endpoints of the Extension Phase are identical …
Key facts
- Sponsor
- Sqy Therapeutics
- Participant type
- Pediatric, Patients
- Age range
- 0-17 years, 18-64 years
- Gender
- Male
- Therapeutic area
- Diseases [C] - Musculoskeletal Diseases [C05]
- Trial duration
- 5 Nov 2025 → ongoing
- Decision date (initial)
- 2022-11-21
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- Yes
- Vulnerable population
- Yes
- Funding sources
- SQY Therapeutics
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Pharmacokinetic, Safety, Pharmacodynamic
Phase 1: Evaluate the safety and tolerability of SQY51 in DMD (Duchenne Muscular Dystrophy) patients.
Phase 2a: Evaluate the safety and tolerance of SQY51 in DMD patients following 49-weeks multiple dosing.
PART III - EXTENSION PHASE : Primary and secondary objectives and endpoints of the Extension Phase are identical of the Phase 2a, with the exception that another muscle biopsy will not be performed.
Secondary objectives 6
- For phase 1 study: Characterize the PK profile of SQY51 and its main metabolites in serum and urine
- For phase 1 study: Determine the effect of SQY51 on specific serum biomarkers
- For phase 2a study: Determine the biodistribution of SQY51 and its main metabolites in serum and urine as well as in skeletal muscle of muscle biopsy at end of Part II
- For phase 2a study: Determine the potential benefit of SQY51 on motor, respiratory and cardiac functions compared to baseline status as well as historical cohorts
- For phase 2a study: Determine the effect of SQY51 on: - dystrophin rescue in muscle biopsy - muscle biomarkers compared to baseline status - quality of life compared to baseline status
- PART III - EXTENSION PHASE : Primary and secondary objectives and endpoints of the Extension Phase are identical of the Phase 2a, with the exception that another muscle biopsy will not be performed.
Conditions and MedDRA coding
Duchenne muscular dystrophy
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.0 | PT | 10013801 | Duchenne muscular dystrophy | 100000004850 |
Study design 3 periods
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Phase 1 All included patients will receive SQY51 intravenously administered once a week in ascending doses (2, 4, 6, 10, 16 and 25 mg/kg).
|
Not Applicable | None | ||
| 2 | Phase 2a Phase 2a includes eight blocks of 2-week treatment with the study drug, each block interspaced by a period of minimum 4 weeks without treatment.
Patients will be allocated to one of three cohorts:
The first cohort, consisting of 4 to maximal 6 patients, will receive a dose of 10 mg/kg/adm or the maximal dose <10 mg/kg that was determined safe during phase 1.
In the second cohort, 3-4 patients will receive 16 mg/kg/adm.
In the third cohort, 3-4 patients will be administered 25 mg/kg/adm.
Cohorts will be constructed as homogenously as possibly with available patients (e.g., or dose ≤ to the dose inducing Cmax and AUC values corresponding to NHP at the NOAEL dose).
|
Not Applicable | None | ||
| 3 | Part III At the end of the phase 2a, patients will either enter an extension phase and continue to be dosed with SQY51, or being long-term followed at regular intervals
|
Not Applicable | None |
Regulatory references
- Scientific advice from competent authorities
- European Medicines Agency
- Plan to share IPD
- No
| EU CT number | Title | Sponsor |
|---|---|---|
| 2022-500703-49-00 | Phase 1/2a, Monocentric, Open Label Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of SQY51 in Paediatric and Adult Patients with a Genetically Confirmed Diagnosis of Duchenne Muscular Dystrophy, including a i) 13-week Phase 1 Multiple Dose Escalation Phase, and a ii) 32-week Phase 2a | Sqy Therapeutics |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 13
- Boys ≥6 years of age and ≥16 kg body weight.
- Being affiliated with a Social Security.
- Informed consent form signed by the patient or, if minor, by the legal guardian(s).
- For phase 2a study: Must have completed Phase 1 of the study.
- Ambulatory or non-ambulatory status, described as Ambulatory stage: Able to rise from the floor and able to walk 10 m without assistance (inclusion of at least 4 patients). Early non-ambulatory stage: Unable to walk 10 m without assistance, including human assistance. Loss of ambulation (LoA) ≤ 5 years preceding enrolment (inclusion of maximal 8 patients). Late non-ambulatory stage: LoA > 5 years preceding enrolment (inclusion of maximal 3 patients).
- Patients and, if minor, their legal guardians who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
- Diagnosed with DMD, genotypically confirmed with DMD mutations amenable to exon-51 skipping.
- Stable hepatic and renal function: • GGT <1.5×ULN, AST <25×ULN, ALT <15×ULN • Total bilirubin <1.5×ULN. • Alkaline phosphatase ≤1.5×ULN. • Estimated glomerular filtration rate ≥90 mL/min/1.73m2. • Proteinuria and microalbuminuria ≤ULN.
- Echocardiography left ventricular ejection fraction (LVEF) at screening ≥40%.
- Concomitant regular treatment with corticosteroids (Prednisone or Deflazacort on daily, alternative or intermittent dosing) for at least three months prior enrolment. Corticosteroid treatment is expected to remain stable during the study, however, can be dose/drug adapted according to weight change of patients.
- If clinically indicated, approved concomitant treatment within standards of care guidelines for DMD, such as antihypertensive, vasodilators, lipid-lowering, thyroid replacement, vitamins, mineral substitution, gastric protectors, nutritional supplements. Patients on the therapies are eligible only if they are on a stable dose for at least one month prior to enrolment until completion of part 2. These treatments can be initiated or adapted as clinically indicated throughout the study.
- Non-invasive mechanical nocturnal ventilation is permissive if <16 h/day.
- For the extension phase : Patients must have completed Phase 2a of the study.
Exclusion criteria 10
- Patient with any serious medical/surgical or psychiatric condition/illness/history that in the opinion of the investigator would jeopardize patient’s safety or would interfere with the study assessments/results, including insufficient obligatory vaccination against infectious diseases as recommended by national guidelines, medical history of infection with Hepatitis B,C and HIV
- Patient with a history of significant allergic reactions and with any known allergies to products likely to be used in the study (e.g., antiseptics, anaesthetics), known hypersensitivity to any of the ingredients, or excipients of the study drug.
- Patient who participated in other investigational study within the last three months, including those with investigational drugs that aim at restoring dystrophin expression such as other antisense oligomers.
- Patient that received gene therapy.
- Patient with intellectual disability or behavioral problem such that they cannot comply with the study procedure.
- Patient with advanced cardiomyopathy and LVEF <40%. Patients with dysrhythmias and being treated for dysrhythmias. Patients with nontreated tachycardia.
- Patient for whom major orthopedic surgery is planned during the phase 1 of the study (little invasive procedures such as tenotomy are permissible during phase 2, any procedure is permissible during the extension phase).
- Tracheostomized patients and dependent on invasive mechanical ventilation. Non-invasive mechanical ventilation ≥ 16 h/day. Medical history with more than two respiratory decompensations requiring hospitalization during the previous year. No respiratory decompensation in the four months preceding enrolment.
- Patients on medications that can restore dystrophin expression, tamoxifen and other drugs without indication for DMD or pediatric population.
- Abnormal laboratory values in the clinically significant range
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 2
- Type, frequency, severity, timing and relationship to SQY51 of: Adverse events (AEs), discontinuations due to AEs, serious AEs (SAEs).
- PART III - EXTENSION PHASE : Primary and secondary objectives and endpoints of the Extension Phase are identical of the Phase 2a, with the exception that another muscle biopsy will not be performed.
Secondary endpoints 10
- Phase 2 : Motor function: - Motor Function Measure (MFM) score for ambulant and non-ambulant patients. - Performance Upper Limb (PUL) scale for ambulant and non-ambulant patients. - 6-minute walk test for ambulant patients. - 1-minute walk test (included in the 6-minute walk test) for ambulant patients. - 10-meter run/walk time for ambulant patients. - Rise from the floor for ambulant patients.
- Phase 2: Respiratory function: -Vital capacity, forced vital capacity, inspiratory capacity, and expiratory residual volume, functional residual capacity, residual volume, total lung capacity, all absolute values as well as percent predicted, as well as forced expiratory flow during 1 s, peak expiratory flow, peak cough flow, Tiffeneau index. -Maximal inspiratory and expiratory pressures, and sniff nasal inspiratory pressure all absolute values as well as % predicted. - Twitch mouth pressure
- Phase 2 : Cardiac function : - echocardiography (LVEDD, LVESD, LVSWT, LVPWT, GLS, LVEFMS, LVMI, mitral inflow velocities, DT, E/é, LAVI, TAPSE, RV s', sPAP) - cardiac MRI (LVEDD, RVEDD, LVESD, RVESD, LVEF, RVEF, LGE, GCS, GRS, LVEDV, LVESV, systolic ejection volume, TAPSE, native T1, T2, ECV).
- Phase 2 : Muscle strength: Measurements of pinch, maximal isometric grip strength using MyoGrip as well as strength of elbow flexion and extension, and knee flexion and extension using hand-held dynamometry.
- Phase 2 : Quality of Life Endpoints/Self-Assessment: Pediatric Quality of Life Inventory (PedsQL) – DMD module
- Phase 2 : Serum biomarker analysis: Muscle necrosis biomarkers (CPK and Myomesine-3).
- Phase 2 : Muscle biomarkers: - Levels of DMD exon-51 transcripts, dystrophin protein, histopathology of muscle biopsy. Lean cross-sectional areas (lCS), fat fraction (FF) and water T2 using quantitative MRI of forearm and lower leg (all patients).
- Phase 1: Levels of SQY51, its main metabolites in serum and urine, and AUC calculation.
- Phase 2: Levels of SQY51 and main metabolites in serum, urine and muscle biopsy sample
- PART III - EXTENSION PHASE : Primary and secondary objectives and endpoints of the Extension Phase are identical of the Phase 2a, with the exception that another muscle biopsy will not be performed.
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Sqy Therapeutics
- Sponsor organisation
- Sqy Therapeutics
- Address
- 50 Allee De Chaponval
- City
- Noisy Le Roi
- Postcode
- 78590
- Country
- France
Scientific contact point
- Organisation
- Sqy Therapeutics
- Contact name
- Scientific advisor
Public contact point
- Organisation
- Sqy Therapeutics
- Contact name
- Clinical Operations Director - Pharmaceuticals
Third parties 2
| Organisation | City, country | Duties |
|---|---|---|
| Biotrial ORG-100006463
|
Rennes, France | On site monitoring, Code 10, Code 11, Code 12, Code 5, Data management, E-data capture, Code 8 |
| Unite Paramedicale Ambulatoire De Recherche Clinique ORG-100050242
|
Paris, France | Other |
Locations
1 EU/EEA country · 1 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| France | Ongoing, recruiting | 12 | 1 |
| Rest of world | — | 0 | — |
Investigational sites
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| France | 2023-01-05 | 2023-04-26 |
Oversight and notifications
Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77
Temporary halts 2 · Art. 38 CTR
Temporary halt TH-17341
- Halt date
- 2024-03-15
- Member states concerned
- France
- Publication date
- 2024-03-15
- Reason
- Medicinal Product related
- Explanation
- Following an analysis of the batch records (carried out on 12/03/2024) of the finished product SQY51 used in the AVANCE 1 phase 1 clinical study (1st patient included in the study on 03/05/2023) and stability data, SQY Therapeutics discovered a non-compliance regarding the expiry dates of batch DPSQYM001 (packaged in 3 sub-batches).
Below is the information recorded in the batch certificates - investigational medicinal product for human use issued by COLCA /EUROMED PHARMA:
- Lot DPSQYM001A expiry date 06/2023, batch certificate signed by QP on 20/12/2022
- Lot DPSQYM001B expiry date 05/2024, batch certificate signed by QP on 14/09/2023
- Lot DPSQYM001C expiry date 05/2024, batch certificate signed by QP on 14/09/2023
SQY51 Finished Product Information:
- Absence of a technical batch for SQY51 performed prior to the start of the clinical study
- 1st batch of SQY 51 DPSQYM001 manufactured at GTP Bioways on 24/11/2021 then packaged and certified for the clinical study by EUROMED PHARMA (ex COLCA) on 20/12/2022 (batch DPSQYM001A), expiry date of certificate 06/2023
- Stabilization of the DPSQYM001 batch at AXOLABS in July 2022 according to the following scheme (Q0 "analytical" = 27/07/2022):
o Normal conditions / Storage in stability chamber at -20°C +/- 5°C / T0 + T3M + T6M + T9M + T12M + T18M + T24M
o Accelerated conditions / Storage in stability chamber at +5°C +/- 3°C / T0 + T2M + T4M + T6M + T9M + T12M + T18M + T24M
o Stress test / Storage in stability chamber at +40°C +/- 2°C / T0 + T1M
- Stability results known to date: stress test +40°C +/- 2°C up to T1M, accelerated conditions at +5°C +/- 3°C up to T12M, and normal conditions at -20°C +/- 5°C up to T12M. To date, no OOS has been detected at any of the check-ins.
- Extrapolation of stability data is not applicable for SQY51 because the product is stored at -20°C (in accordance with ICH Q1E – Evaluation of stability data)
In fact, you will find below the expiry dates that should have been entered on the different dates of issue of the certificates of the batch DPSQYM001 in view of the state of knowledge (stability results and exclusion of extrapolation):
- Expiry date 11/2022, on the date of signature of the batch certificate on 20/12/2022
- Expiry Date 07/2023, on the date of signature of the batch certificate on 14/09/2023
Please also note that this non-compliance cannot be considered a public health concern as no serious adverse reactions were reported in the Phase 1 study.
Following the observation of this non-compliance, SQY Therapeutics immediately requested that the DPSQYM001 batch be quarantined on 13/03/2024 within the pharmacy of the investigator site.
The last administration of this batch took place at the investigator site on 11/03/2024 as part of this AVANCE 1 - phase 1 study.
This Phase 1 study has not been yet finalized. Upcoming visits are described in Appendix 1 of the attached letter.
Currently, there is another batch of SQY51 finished product, never administered to humans, batch DPSQYM002 manufactured on 27/09/2022 with an expiry date of 05/2024 (batch certificate signed on 23/10/2023) : expiry date in line with the stability data known to date. The 18-month stability data is expected to be confirmed by 22/03/2024.
Part of this batch has been sent to the investigator site, but no administration will take place without the authorization of the ANSM.
SQY Therapeutics is aware of the seriousness of this non-compliance and inform you that a deviation has been put in place in order to implement emergency actions, a deviation involving the CRO BIOTRIAL, the investigator site and EUROMED PHARMA, all of whom have been informed of this notification. - Follow-up measures
- This same notification will be the subject of an email communication.
The actions SQY Therapeutics intends to implement are as follows:
- Suspension of the administration of SQY51 in the context of the AVANCE 1 – phase 1 clinical study pending feedback from the ANSM for the continuation of the study with the administration of batch DPSQYM002. 18-month stability data for batch DPSQYM002 is expected to be available by 22/03/2024.
- Continuation of analyses, recruitment and follow-up visits of the AVANCE 1 – Phase 1 clinical study, as mentioned in Appendix 1.
- Emergency analysis of the remaining vials of the batch DPSQYM001
- Communication with patients after approval by the ANSM
- Communication with the DSMB/steering committee after approval by the ANSM
- Communication with the hospital of the investigator site after approval by the ANSM - Benefit-risk balance changed
- No
- Treatment stopped
- Yes
Temporary halt TH-76448
- Halt date
- 2025-03-14
- Member states concerned
- France
- Publication date
- 2025-03-26
- Reason
- Safety related (clinical or pre-clinical results)
- Explanation
- The AVANCE1 phase 1/2a trial has temporarily paused injections as a precaution to fully assess recent SUSARs in three patients (one with potential treatment-related proteinuria, one with a Grade 4 Cerebral Venous Thrombosis, and one with Polycythemia).
This decision, made with the Steering Committee on March 14, 2025, necessitates a thorough protocol review to refine treatment suspension/discontinuation criteria. While these events haven't changed the benefit/risk ratio, they were unexpected for the SQY51.
Please refer to the attached Cover letter for a detailed overview.
Attached are CIOMS forms for patients 01-015 and 01-008 and 01-002.
Data collection will continue despite the injection pause, and advancing biopsies for near-completion patients is proposed. - Follow-up measures
- A DSMB meeting was held on March 21st to discuss these events and potential measures, meeting minutes are ongoing.
A letter was addressed to the Principal Investigator on the 19th March 2025 for this temporary halt (please see attached). All patients were informed of these injections temporary halt by the Principal Investigator.
Encouragingly, early pharmacodynamic data shows reduced DMD-associated serum biomarkers, and the first completed patient's muscle biopsy revealed dystrophin restoration and stable ambulatory function. Ex-vivo studies support these findings, indicating SQY51's potential to normalize key muscle-related pathways. The observed polycythemia might even suggest a beneficial normalization of dystrophic musculature. Consequently, adjustments to SQY51 dosage, injection frequency, and treatment criteria are being considered, alongside intensified biomarker monitoring.
An urgent meeting with the Agency is requested to discuss this data, protocol adjustments, and the continuation of treatment for favorable responders.
Finally, an extension is requested for the substantial protocol amendment submission deadline (currently April 14thfollowing DSUR RFIs).
A USM is submitted in parallel of this notification - Benefit-risk balance changed
- No
- Treatment stopped
- Yes
Urgent safety measures 2 · Art. 54 CTR
Urgent safety measure US-51783
- Event date
- 2024-10-04
- Submission date
- 2024-10-15
- In response to
- OTHER
- Member states affected
- France
- Event description
- As indicated in e-mails sent to ANSM on 07/10/2024 and 14/10/2024, analysis of the areas under the curve (AUC) of patients who completed Part I, suggests the possibility of overexposure to the investigational medicinal product, SQY51, in the heaviest patients, due to the method used to calculate the dose administered: mg/kg. As such, this is a potential risk of overexposure to the investigational medicinal product detected on 30/09/2024.
On the same day, members of the Data and Safety Monitoring Board (DSMB) and experts from the Comité de Pilotage, including a methodologist and a pharmacokineticist, met to discuss the reassignment of patients to the cohorts, based on analyses of the pharmacokinetic (PK) data evaluated in Part I of the study.
On the basis of these observations, which are also provided for in the protocol, it appears essential to consider blood volume and individual AUC as key criteria to be taken into account before patients are reassigned to the three cohorts in Part II. - Measures taken
- In the absence of a major adverse event, and in order to eliminate any risk of overexposure in the heaviest patients, even if the risk has not been confirmed, it is necessary to readjust the reassignment of patients in a safe manner. The experts on the steering committee therefore suggest the following allocation:
- Cohort 10 mg/kg : 6 participants (including 4 of the heaviest) ;
- Cohort 16 mg/kg: 3 participants;
- Cohort 25 mg/kg: 3 participants.
DSMB members approved this reassignment. This urgent safety measure will be endorsed by a substantial modification for authorization.
Urgent safety measure US-76442
- Event date
- 2025-03-18
- Submission date
- 2025-03-26
- In response to
- OTHER
- Member states affected
- France
- Event description
- The AVANCE1 phase 1/2a trial has temporarily paused injections as a precaution to fully assess recent SUSARs in three patients (one with potential treatment-related proteinuria, one with a Grade 4 Cerebral Venous Thrombosis, and one with Polycythemia).
This decision, made with the Steering Committee on March 14, 2025, necessitates a thorough protocol review to refine treatment suspension/discontinuation criteria. While these events haven't changed the benefit/risk ratio, they were unexpected for the SQY51.
Please refer to the attached Cover letter for a detailed overview.
Attached are CIOMS forms for patients 01-015 and 01-008 and a SAE narrative for the patient 01-002 (CIOMS will be available by 26-MAR-2025).
Data collection will continue despite the injection pause, and advancing biopsies for near-completion patients is proposed. - Measures taken
- Data collection will continue despite the injection pause, and advancing biopsies for near-completion patients is proposed.
A DSMB meeting was held on March 21st to discuss these events and potential measures, meeting minutes are ongoing.
A letter was addressed to the Principal Investigator on the 19th March 2025 for this temporary halt (please see attached). All patients were informed of these injections temporary halt by the Principal Investigator.
Encouragingly, early pharmacodynamic data shows reduced DMD-associated serum biomarkers, and the first completed patient's muscle biopsy revealed dystrophin restoration and stable ambulatory function. Ex-vivo studies support these findings, indicating SQY51's potential to normalize key muscle-related pathways. The observed polycythemia might even suggest a beneficial normalization of dystrophic musculature. Consequently, adjustments to SQY51 dosage, injection frequency, and treatment criteria are being considered, alongside intensified biomarker monitoring.
An urgent meeting with the Agency is requested to discuss this data, protocol adjustments, and the continuation of treatment for favorable responders.
Finally, an extension is requested for the substantial protocol amendment submission deadline (currently April 14thfollowing DSUR RFIs).
A temporary halt is submitted in parallel of this notification. - Justification
- CTIS bug
Application history
9 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2022-08-12 | France | Acceptable 2022-11-15
|
2022-11-21 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2023-02-15 | France | Acceptable 2023-03-31
|
2023-04-11 |
| 3 | SUBSTANTIAL MODIFICATION | SM-2 | 2023-12-06 | France | Acceptable 2024-03-18
|
2024-03-25 |
| 4 | SUBSTANTIAL MODIFICATION | SM-3 | 2024-05-22 | France | Acceptable 2024-07-04
|
2024-07-04 |
| 5 | SUBSTANTIAL MODIFICATION | SM-4 | 2024-10-22 | France | Acceptable 2024-11-15
|
2024-11-15 |
| 6 | SUBSTANTIAL MODIFICATION | SM-5 | 2024-12-11 | France | Acceptable 2024-12-23
|
2024-12-23 |
| 7 | SUBSTANTIAL MODIFICATION | SM-6 | 2025-07-16 | France | Acceptable 2025-09-16
|
2025-09-16 |
| 8 | SUBSTANTIAL MODIFICATION | SM-7 | 2025-09-19 | France | Acceptable | 2025-10-22 |
| 9 | SUBSTANTIAL MODIFICATION | SM-8 | 2026-01-28 | France | Acceptable | 2026-02-27 |