Spastic Paraplegia Type 50Phase 1NCT06069687
Administration of MELPIDA to Determine the Safety and Efficacy for Patients With Spastic Paraplegia Type 50
A Phase 1 study testing MELPIDA in people with Spastic Paraplegia Type 50, run by The Hospital for Sick Children at 1 site in Canada.
Trial summary
This will be a first-in-human Phase I, open-label, single dose clinical study of MELPIDA administered intrathecally (IT) through a lumbar puncture (LP) to a single subject with confirmed pathogenic mutations in the Adaptor Related Protein Complex 4 Subunit Mu 1 (AP4M1) gene. Read more about this study
- Who is it for?
- Ages 0 to 4 years, men only
- Conditions the study is for
- Spastic Paraplegia Type 50
- What is being tested?
- MELPIDA
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteCanada
- Study dates
- 11 Mar 2022to Mar 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 0 to 4 years
- Men only
- No healthy volunteers
- Child
Who may be able to join
- Age < 5 years old
- Confirmed diagnosis of SPG50 disease by:
- Genomic DNA mutation analysis demonstrating homozygous or compound heterozygous, pathogenic and/or potentially pathogenic variants in the AP4M1 gene
- Clinical history or examination features consistent with SPG50 and that include neurologic dysfunction
- Parent/legal guardian willing to provide written informed consent for their child prior to participation in the study
- Subject able to comply with all protocol requirements and procedures
Who cannot join
- Inability to participate in study procedures (as determined by the site investigator)
- Presence of a concomitant medical condition that precludes lumbar puncture (LP) or use of anesthetics
- History of bleeding disorder or any other medical condition or circumstance in which lumbar puncture is contraindicated according to local institutional policy
- Inability to be safely sedated in the opinion of the clinical anesthesiologist
- Active infection, at the time of dosing, based on clinical observations
- Concomitant illness or requirement for chronic drug treatment that in the opinion of the PI creates unnecessary risks for gene transfer
Show all 14Show fewer
- Inability of the patient to undergo MRI according to local institutional policy
- Inability of the patient to undergo any other procedure required in this study
- The presence of significant non-SPG50 related central nervous system (CNS) impairment or behavioral disturbances that would confound the scientific rigor or interpretation of results of the study
- Have received an investigational drug within 30 days prior to screening or plan to receive an investigational drug (other than gene therapy) during the study.
- Enrollment and participation in another interventional clinical trial
- Contraindication to MELPIDA or any of its ingredients
- Contraindication to any of the immune suppression medications used in this study
- Clinically significant abnormal laboratory values (GGT, ALT, and AST, or total bilirubin > 3 × Upper Limit of Normal (ULN), creatinine ≥ 1.5 mg/dL, hemoglobin [Hgb] < 6 or > 20 g/dL; white blood cell (WBC) > 20,000 per cmm) prior to gene replacement therapy. Patients with an elevated bilirubin level that is unequivocally the result of neonatal jaundice shall not be excluded
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 1 Open-label Intrathecal Administration of MELPIDA to Determine the Safety and Efficacy for Patients With Spastic Paraplegia Type 50 (SPG50) Caused by a Mutation in the AP4M1 Gene
This will be a first-in-human Phase I, open-label, single dose clinical study of MELPIDA administered intrathecally (IT) through a lumbar puncture (LP) to a single subject with confirmed pathogenic mutations in the Adaptor Related Protein Complex 4 Subunit Mu 1 (AP4M1) gene. The primary outcome will be the determination of the safety and tolerability of MELPIDA in patients with SPG50, based on development of toxicity.
The secondary outcome will be a preliminary exploration of efficacy of the treatment.
Read more
MELPIDA, is a recombinant serotype 9 adeno-associated virus (AAV) encoding a codon-optimized human AP4M1 transgene and will be administer to the patient via a single intrathecal infusion of 10 mL at 1E14 vg/mL for a total dose of 1E15 vg.
The total study duration is 5 years post dosing and the participant will be tested at screening/baseline (-28 to -7 days), return for dosing, and then follow-up visits post-dosing on Days 7 (+/-2), 30 (+/-2), 60 (+/-2), 90 (+/-14), 180 (+/-14), 270 (+/-14), 360 (+/-14), 540 (+/-14), and 720 (+/-14) days, then annually for the last 3 years.
- Conditions
- Spastic Paraplegia Type 50
- Being tested
- MELPIDA
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MELPIDABiological
A single intrathecal infusion of 10 mL at 1E14 vg/mL for a total dose of 1E15 vg
| Study group | Role | What they receive |
|---|---|---|
| MELPIDA | Experimental | A single intrathecal infusion of 10 mL at 1E14 vg/mL for a total dose of 1E15 vg (open-label) Receives: Biological: MELPIDA |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of unanticipated anticipated treatment-related toxicities, Grade 3 or higher
collection of occurrence and severity of serious adverse events. Incidence of serious adverse events and adverse events throughout the study, as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Higher grade values indicated greater severity. Grade 1 - Grade 5.
Measured: through study completion, an average of 5 years
Change from baseline in nerve conduction velocity
Nerve conduction studies will be used to determine nerve conduction velocity. Nerve conduction studies involve providing a small electrical stimulus to either a motor or sensor nerve and then measuring the resulting action potential at distal point of that nerve (for sensory nerve studies) or at the muscle that the nerve innervates (motor nerve studies). Velocity of conduction (measured between the two points and represented in m/s) will be obtained. The value is compared to standard reference values for age.
Measured: Screening, Day 21, and Month 3, 6, 12, 24, 36, 48 and 60
Determination of liver safety
Changes in Liver Ultrasound findings from baseline. Incidence of serious adverse events and adverse events throughout the study, as assessed by CTCAE v5.0
Measured: Screening, Month 6, 12, 24, 36, 48 and 60
Determination of liver safety
Liver laboratory test: alanine transaminase (ALT) in U/L
Measured: Screening, Day -1, 2, 7, 14, 21 and 28, and Month 3, 6, 9, 12, 18, 24, 36, 48 and 60
Determination of liver safety
Liver laboratory test: aspartate aminotransferase (AST) in U/L
Measured: Screening, Day -1, 2, 7, 14, 21 and 28, and Month 3, 6, 9, 12, 18, 24, 36, 48 and 60
determination of liver safety
Liver laboratory test: Total bilirubins in umol/L
Measured: Screening, Day -1, 2, 7, 14, 21 and 28, and Month 3, 6, 9, 12, 18, 24, 36, 48 and 60
Determination of liver safety
Liver laboratory test: direct bilirubins in umol/L
Measured: Screening, Day -1, 2, 7, 14, 21 and 28, and Month 3, 6, 9, 12, 18, 24, 36, 48 and 60
Determination of liver safety
Liver laboratory test: alkaline phosphatase (ALP) in U/L
Measured: Screening, Day -1, 2, 7, 14, 21 and 28, and Month 3, 6, 9, 12, 18, 24, 36, 48 and 60
Determination of liver safety
Liver laboratory test: gamma-glutamyl transferase (GGT) in U/L
Measured: Screening, Day -1, 2, 7, 14, 21 and 28, and Month 3, 6, 9, 12, 18, 24, 36, 48 and 60
Change from baseline in nerve conduction amplitude
Nerve conduction study will be done to assess nerve conduction amplitude. Nerve conduction studies involve providing a small electrical stimulus to either a motor or sensor nerve and then measuring the resulting action potential at distal point of that nerve (for sensory nerve studies) or at the muscle that the nerve innervates (motor nerve studies). Amplitude of the action potential (measured at the distal site and represented in uV for sensory amplitudes and mV for motor amplitudes) will be obtained. The value is compared to standard reference values for age.
Measured: Screening, Day 21, and Month 3, 6, 12, 24, 36, 48 and 60
Secondary outcomes (2)
Stability or improvement in spasticity
Modified Ashworth scale (0-4). 0: no increase in muscle tone; 1: slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion when the affected part(s) is moved in flexion or extension; 1+: slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the range of motion; 2: more marked increase in muscle tone through most of the range of motion, but affected part(s) easily moved; 3: considerable increase in muscle tone, passive movement difficult; 4: affected part(s) rigid in flexion or extension. Values reported separately for right and left upper and lower limbs.
Measured: Screening, Day -1, and Month 3, 6, 9, 12, 18, 24, 36, 48 and 60.
Stability or improvement in spasticity
Tardieu scale (0-5). 0: no resistance throughout passive movement; 1: slight resistance throughout with no clear catch at a precise angle; 2: clear catch at a precise angle, followed by release; 3: fatiguable clonus (<10 seconds) occurring at a precise angle; 4: unfatiguable clonus (>10 seconds) occurring at a precise angle; 5: joint immobile. Values reported separately for right and left upper and lower limbs.
Measured: Screening, Day -1, and Month 3, 6, 9, 12, 18, 24, 36, 48 and 60.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Oct 2023
- Study start11 Mar 2022
- Primary completionMar 2027 (estimated)
- Study completionMar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Spastic Paraplegia Type 50Studies of the same condition, open and under way.
- More trials run by The Hospital for Sick ChildrenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Hospital for Sick Children
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Gregory Costain, The Hospital for Sick Children
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06069687
- Sponsor's protocol ID
- 1000079110
- Status last verified
- May 2025
- First submitted
- 17 Aug 2023
- Last updated
- 14 May 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Dowling JJ, Pirovolakis T, Devakandan K, Stosic A, Pidsadny M, Nigro E, Sahin M, Ebrahimi-Fakhari D, Messahel S, Varadarajan G, Greenberg BM, Chen X, Minassian BA, Cohn R, Bonnemann CG, Gray SJ. AAV gene therapy for hereditary spastic paraplegia type 50: a phase 1 trial in a single patient. Nat Med. 2024 Jul;30(7):1882-1887. doi: 10.1038/s41591-024-03078-4. Epub 2024 Jun 28.
PubMed 38942994
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Open-label Intrathecal Administration of MELPIDA to Determine the Safety and Efficacy for Patients With Spastic Paraplegia Type 50 (SPG50) Caused by a Mutation in the AP4M1 Gene
- ClinicalTrials.gov ID
- NCT06069687
- Acronym / sponsor ID
- 1000079110
- Conditions
- Spastic Paraplegia Type 50
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 1 participants (actual)
- Lead sponsor
- The Hospital for Sick ChildrenUniversity, hospital or other
- Study start
- 11 Mar 2022 (actual)
- Primary completion
- Mar 2027 (estimated)
- Study completion
- Mar 2027 (estimated)
- First posted
- 6 Oct 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This will be a first-in-human Phase I, open-label, single dose clinical study of MELPIDA administered intrathecally (IT) through a lumbar puncture (LP) to a single subject with confirmed pathogenic mutations in the Adaptor Related Protein Complex 4 Subunit Mu 1 (AP4M1) gene. The primary outcome will be the determination of the safety and tolerability of MELPIDA in patients with SPG50, based on development of toxicity.
The secondary outcome will be a preliminary exploration of efficacy of the treatment.
MELPIDA, is a recombinant serotype 9 adeno-associated virus (AAV) encoding a codon-optimized human AP4M1 transgene and will be administer to the patient via a single intrathecal infusion of 10 mL at 1E14 vg/mL for a total dose of 1E15 vg.
The total study duration is 5 years post dosing and the participant will be tested at screening/baseline (-28 to -7 days), return for dosing, and then follow-up visits post-dosing on Days 7 (+/-2), 30 (+/-2), 60 (+/-2), 90 (+/-14), 180 (+/-14), 270 (+/-14), 360 (+/-14), 540 (+/-14), and 720 (+/-14) days, then annually for the last 3 years.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| MELPIDA | Experimental | Biological: MELPIDAA single intrathecal infusion of 10 mL at 1E14 vg/mL for a total dose of 1E15 vg (open-label) |
Who may qualify
- Ages
- 0 to 4 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- Age < 5 years old
- Confirmed diagnosis of SPG50 disease by:
- Genomic DNA mutation analysis demonstrating homozygous or compound heterozygous, pathogenic and/or potentially pathogenic variants in the AP4M1 gene
- Clinical history or examination features consistent with SPG50 and that include neurologic dysfunction
- Parent/legal guardian willing to provide written informed consent for their child prior to participation in the study
Key exclusion criteria (14 listed)
- Inability to participate in study procedures (as determined by the site investigator)
- Presence of a concomitant medical condition that precludes lumbar puncture (LP) or use of anesthetics
- History of bleeding disorder or any other medical condition or circumstance in which lumbar puncture is contraindicated according to local institutional policy
- Inability to be safely sedated in the opinion of the clinical anesthesiologist
- Active infection, at the time of dosing, based on clinical observations
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MELPIDAA single intrathecal infusion of 10 mL at 1E14 vg/mL for a total dose of 1E15 vg | Biological | MELPIDA |
Primary outcome
Incidence of unanticipated anticipated treatment-related toxicities, Grade 3 or higher
Time frame: through study completion, an average of 5 years
collection of occurrence and severity of serious adverse events. Incidence of serious adverse events and adverse events throughout the study, as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Higher grade values indicated greater severity. Grade 1 - Grade 5.
Change from baseline in nerve conduction velocity
Time frame: Screening, Day 21, and Month 3, 6, 12, 24, 36, 48 and 60
Nerve conduction studies will be used to determine nerve conduction velocity. Nerve conduction studies involve providing a small electrical stimulus to either a motor or sensor nerve and then measuring the resulting action potential at distal point of that nerve (for sensory nerve studies) or at the muscle that the nerve innervates (motor nerve studies). Velocity of conduction (measured between the two points and represented in m/s) will be obtained. The value is compared to standard reference values for age.
Determination of liver safety
Time frame: Screening, Month 6, 12, 24, 36, 48 and 60
Changes in Liver Ultrasound findings from baseline. Incidence of serious adverse events and adverse events throughout the study, as assessed by CTCAE v5.0
Determination of liver safety
Time frame: Screening, Day -1, 2, 7, 14, 21 and 28, and Month 3, 6, 9, 12, 18, 24, 36, 48 and 60
Liver laboratory test: alanine transaminase (ALT) in U/L
Determination of liver safety
Time frame: Screening, Day -1, 2, 7, 14, 21 and 28, and Month 3, 6, 9, 12, 18, 24, 36, 48 and 60
Liver laboratory test: aspartate aminotransferase (AST) in U/L
determination of liver safety
Time frame: Screening, Day -1, 2, 7, 14, 21 and 28, and Month 3, 6, 9, 12, 18, 24, 36, 48 and 60
Liver laboratory test: Total bilirubins in umol/L
Determination of liver safety
Time frame: Screening, Day -1, 2, 7, 14, 21 and 28, and Month 3, 6, 9, 12, 18, 24, 36, 48 and 60
Liver laboratory test: direct bilirubins in umol/L
Determination of liver safety
Time frame: Screening, Day -1, 2, 7, 14, 21 and 28, and Month 3, 6, 9, 12, 18, 24, 36, 48 and 60
Liver laboratory test: alkaline phosphatase (ALP) in U/L
Determination of liver safety
Time frame: Screening, Day -1, 2, 7, 14, 21 and 28, and Month 3, 6, 9, 12, 18, 24, 36, 48 and 60
Liver laboratory test: gamma-glutamyl transferase (GGT) in U/L
Change from baseline in nerve conduction amplitude
Time frame: Screening, Day 21, and Month 3, 6, 12, 24, 36, 48 and 60
Nerve conduction study will be done to assess nerve conduction amplitude. Nerve conduction studies involve providing a small electrical stimulus to either a motor or sensor nerve and then measuring the resulting action potential at distal point of that nerve (for sensory nerve studies) or at the muscle that the nerve innervates (motor nerve studies). Amplitude of the action potential (measured at the distal site and represented in uV for sensory amplitudes and mV for motor amplitudes) will be obtained. The value is compared to standard reference values for age.
2 secondary outcomes
Stability or improvement in spasticity
Time frame: Screening, Day -1, and Month 3, 6, 9, 12, 18, 24, 36, 48 and 60.
Stability or improvement in spasticity
Time frame: Screening, Day -1, and Month 3, 6, 9, 12, 18, 24, 36, 48 and 60.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2025.
- Derived from this study: PubMed 38942994Dowling JJ, Pirovolakis T, Devakandan K, Stosic A, Pidsadny M, Nigro E, Sahin M, Ebrahimi-Fakhari D, Messahel S, Varadarajan G, Greenberg BM, Chen X, Minassian BA, Cohn R, Bonnemann CG, Gray SJ. AAV gene therapy for hereditary spastic paraplegia type 50: a phase 1 trial in a single patient. Nat Med. 2024 Jul;30(7):1882-1887. doi: 10.1038/s41591-024-03078-4. Epub 2024 Jun 28.
- Individual participant dataSharing planned: No
Related trials for Spastic Paraplegia Type 50
RecruitingPhase 1/2
Melpida: Recombinant Adeno-associated Virus (Serotype 9) Encoding a Codon Optimized Human AP4M1 Transgene (hAP4M1opt)
Spasticity, Muscle, Microcephaly
RecruitingPhase 3
Phase 3 Efficacy Study With Concurrent Control of IT MELPIDA in SPG50.Concurrent Controls.
Hereditary Spastic Paraplegia Type 50
Not yet recruitingPhase 1/2
Safety and Efficacy of AAV9/AP4B1 (BFB-101) For Patients With AP4B1-related Hereditary Spastic Paraplegia Type 47 (SPG47)
HSP, Hereditary Spastic Paraplegia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MELPIDA in people with Spastic Paraplegia Type 50, run by The Hospital for Sick Children at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 14 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of unanticipated anticipated treatment-related toxicities, Grade 3 or higher (time frame: through study completion, an average of 5 years). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06069687, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 May 2025.