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SMARD1Phase 1/2NCT05152823

Gene Therapy for IGHMBP2-Related Diseases

A Phase 1/2 study testing Gene Therapy in people with SMARD1 and CMT2S, run by Megan Waldrop at 1 site in United States.

Enrolling by invitation

Enrolling by invitation. The study team selects and invites participants, usually from an existing group of patients.

Sites and contacts
Official record
Search all trials

Trial summary

Open-label, single intrathecal injection study of a AAV9 vector carrying the IGHMBP2 gene for IGHMBP2-related diseases. Read more about this study

Who is it for?
Ages 2 months to 14 years
Conditions the study is for
SMARD1, CMT2S
What is being tested?
Gene Therapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
1 siteUnited States
Study dates
4 Nov 2021to Jul 2030
Phase
Phase 1/2
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 2 months to 14 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • Confirmation of two pathogenic variants in the IGHMBP2 gene from a CLIA-certified lab
  • Pre-ambulant (not yet walking and less than 18 months) or ambulant (as defined by the ability to walk 10 meters without assistance) or non-ambulant (inability to walk more than 10 meters unassisted)
  • Ability to cooperate with functional assessments as per PI's discretion

Who cannot join

  • Prior participation in a gene or cell therapy program for any kind.
  • Immunizations of any kind in the month prior to the study.
  • Active infection based on clinical observations
  • Serological evidence of HIV infection, or Hepatitis B or C infection
  • Diagnosis of (or ongoing treatment for) an autoimmune disease
  • Persistent leukopenia or leukocytosis (WBC ≤ 3.5 10^3/μL or ≥ 20.0 10^3/μL) or an absolute neutrophil count < 1.5 10^3/μL
Show all 14Show fewer
  • Abnormal liver function as indicated by an elevated GGT (>2X normal if no other laboratory abnormalities), bilirubin and/or abnormal PT/INR
  • Concomitant illness or requirement for chronic drug treatment that in the opinion of the PI creates unnecessary risks for gene transfer
  • AAV9 binding antibody titers > 1:50 as determined by ELISA immunoassay performed by Athena Diagnostics
  • Abnormal laboratory values in the clinically significant range, based upon normal values in the Nationwide Children's Hospital Laboratory
  • Diagnosis of any other systemic illness that increases the risk of gene transfer per the PI's opinion; Has a medical condition or extenuating circumstance that, in the opinion of the PI, might compromise the subject's ability to comply with the protocol required testing or procedures or compromise the subject's well-being, safety, or clinical interpretability
  • Any requirement for immune modulatory therapy and for which it would be unsafe for the subject to undergo an appropriate wash out period
  • Contraindication for intrathecal injection
  • A positive JCV antibody test of >0.40

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

United States1 site

  • Nationwide Children's Hospital

    Columbus, Ohio, 43205

Other trials in United States

About this study

Official title: Phase I/IIa Intrathecal Gene Delivery Clinical Trial for IGHMBP2-Related Diseases

Open-label, single intrathecal injection study of a AAV9 vector carrying the IGHMBP2 gene for IGHMBP2-related diseases.

Conditions
SMARD1, CMT2S
Being tested
Gene Therapy
Keywords
IGHMBP2
Medical subject headings
Spinal muscular atrophy with respiratory distress 1

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Gene TherapyBiological

    AAV9 carrying the IGHMBP2 gene.

Study groups in NCT05152823
Study groupRoleWhat they receive
Single Intrathecal DeliveryExperimentalNot described
Receives: Biological: Gene Therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Monitoring for the development of unacceptable toxicity.

    Unacceptable toxicity is defined as the occurrence of two or more unexpected Grade III or higher treatment-related toxicities, as defined by CTCAE 5.0.

    Measured: 3 years

Secondary outcomes (4)

  1. For pre-ambulant participants, ages less than 18 months, change in the Neuromuscular Gross Motor Outcome (GRO) from baseline

    Measured: Days 90 and 180, Months 12, 18, 24 and 36

  2. For ambulant participants, change in the 100-meter timed test from baseline

    Measured: Days 90 and 180, Months 12, 18, 24 and 36

  3. For non-ambulant participants, ages 18 months to 6 years, change in the Neuromuscular Gross Motor Outcome (GRO) from baseline

    Measured: Days 90 and 180, Months 12, 18, 24 and 36

  4. For non-ambulant participants, ages greater than 6 years, change in the revised upper limb module for SMA (RULM) from baseline

    Measured: Days 90 and 180, Months 12, 18, 24 and 36

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Dec 2021
  2. Study start4 Nov 2021
  3. Primary completionJul 2028 (estimated)
  4. Study completionJul 2030 (estimated)

Resources

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
10 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05152823
Sponsor's protocol ID
STUDY00002143
Status last verified
Sep 2025
First submitted
25 Nov 2021
Last updated
30 Sep 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Grohmann K, Schuelke M, Diers A, Hoffmann K, Lucke B, Adams C, Bertini E, Leonhardt-Horti H, Muntoni F, Ouvrier R, Pfeufer A, Rossi R, Van Maldergem L, Wilmshurst JM, Wienker TF, Sendtner M, Rudnik-Schoneborn S, Zerres K, Hubner C. Mutations in the gene encoding immunoglobulin mu-binding protein 2 cause spinal muscular atrophy with respiratory distress type 1. Nat Genet. 2001 Sep;29(1):75-7. doi: 10.1038/ng703.

    PubMed 11528396

  • Saladini M, Nizzardo M, Govoni A, Taiana M, Bresolin N, Comi GP, Corti S. Spinal muscular atrophy with respiratory distress type 1: Clinical phenotypes, molecular pathogenesis and therapeutic insights. J Cell Mol Med. 2020 Jan;24(2):1169-1178. doi: 10.1111/jcmm.14874. Epub 2019 Dec 4.

    PubMed 31802621

  • Guenther UP, Handoko L, Varon R, Stephani U, Tsao CY, Mendell JR, Lutzkendorf S, Hubner C, von Au K, Jablonka S, Dittmar G, Heinemann U, Schuetz A, Schuelke M. Clinical variability in distal spinal muscular atrophy type 1 (DSMA1): determination of steady-state IGHMBP2 protein levels in five patients with infantile and juvenile disease. J Mol Med (Berl). 2009 Jan;87(1):31-41. doi: 10.1007/s00109-008-0402-7. Epub 2008 Sep 18.

    PubMed 18802676

  • Viguier A, Lauwers-Cances V, Cintas P, Manel V, Peudenier S, Desguerre I, Quijano-Roy S, Vanhulle C, Fradin M, Isapof A, Jokic M, Mathieu-Dramard M, Dieterich K, Petit F, Magdelaine C, Giuliano F, Gras D, Haye D, Nizon M, Magen M, Bieth E, Cances C. Spinal muscular atrophy with respiratory distress type 1: A multicenter retrospective study. Neuromuscul Disord. 2019 Feb;29(2):114-126. doi: 10.1016/j.nmd.2018.10.002. Epub 2018 Oct 31.

    PubMed 30598237

  • Tomaselli PJ, Horga A, Rossor AM, Jaunmuktane Z, Cortese A, Blake JC, Zarate-Lopez N, Houlden H, Reilly MM. IGHMBP2 mutation associated with organ-specific autonomic dysfunction. Neuromuscul Disord. 2018 Dec;28(12):1012-1015. doi: 10.1016/j.nmd.2018.08.010. Epub 2018 Aug 29.

    PubMed 30385095

  • Eckart M, Guenther UP, Idkowiak J, Varon R, Grolle B, Boffi P, Van Maldergem L, Hubner C, Schuelke M, von Au K. The natural course of infantile spinal muscular atrophy with respiratory distress type 1 (SMARD1). Pediatrics. 2012 Jan;129(1):e148-56. doi: 10.1542/peds.2011-0544. Epub 2011 Dec 12.

    PubMed 22157136

  • Cottenie E, Kochanski A, Jordanova A, Bansagi B, Zimon M, Horga A, Jaunmuktane Z, Saveri P, Rasic VM, Baets J, Bartsakoulia M, Ploski R, Teterycz P, Nikolic M, Quinlivan R, Laura M, Sweeney MG, Taroni F, Lunn MP, Moroni I, Gonzalez M, Hanna MG, Bettencourt C, Chabrol E, Franke A, von Au K, Schilhabel M, Kabzinska D, Hausmanowa-Petrusewicz I, Brandner S, Lim SC, Song H, Choi BO, Horvath R, Chung KW, Zuchner S, Pareyson D, Harms M, Reilly MM, Houlden H. Truncating and missense mutations in IGHMBP2 cause Charcot-Marie Tooth disease type 2. Am J Hum Genet. 2014 Nov 6;95(5):590-601. doi: 10.1016/j.ajhg.2014.10.002. Epub 2014 Oct 30.

    PubMed 25439726

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Gene Therapy in people with SMARD1 and CMT2S, run by Megan Waldrop at 1 site in United States.

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 3 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: enrolling by invitation, as of the sponsor's last update on 30 Sep 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 United States. 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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?

Monitoring for the development of unacceptable toxicity. (time frame: 3 years). 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 NCT05152823, which also lists 7 linked publications.

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 30 Sep 2025.

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