Evaluation of Long-Term Safety and Efficacy of Apitegromab in Patients with Spinal Muscular Atrophy (a genetic condition that causes muscle weakness and atrophy [when muscles get smaller]) Who Have Completed Previous Trials of Apitegromab.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Scholar Rock Inc.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Trial duration

28 Jun 2023 → ongoing

Decision date (initial)

2024-04-11

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Scholar Rock, Inc.

External identifiers

EU CT number

2024-511654-42-00

EudraCT number

2022-001771-14

ClinicalTrials.gov

NCT05626855

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Safety, Pharmacodynamic, Therapy, Pharmacokinetic, Efficacy

Evaluate the long-term safety and tolerability of apitegromab in patients with Type 2 and Type 3 SMA.

Secondary objectives 1

1. Evaluate the long-term efficacy of apitegromab by assessing changes in motor function outcome measures at prespecified time points. Further evaluate the immunogenicity of apitegromab

Conditions and MedDRA coding

Spinal Muscular Atrophy (SMA)

Study design 2 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-002951-PIP02-21

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Informed consent document signed by the patient if the patient is legally an adult. If the patient is legally a minor, informed consent document signed by the patient's parent or legal guardian and patient's oral or written assent obtained, if applicable and in accordance with the regulatory and legal requirements of the participating location.
2. Patients who have completed the Phase 2 TOPAZ (Study SRK-015-002) trial or the Phase 3 SAPPHIRE (Study SRK-015-003) trial.
3. Estimated life expectancy >2 years from Baseline (Day 1).
4. Able to receive study drug infusions and provide blood samples through the use of a peripheral IV or a long-term IV access device that the patient has placed for reasons independent from the trial (i.e., for background medical care and not for the purpose of receiving apitegromab in the trial), throughout the trial.
5. Able to adhere to the requirements of the protocol.
6. Females of childbearing potential must have a negative pregnancy test at Baseline and agree to use at least 1 acceptable method of contraception throughout the trial and for 20 weeks after the last dose of apitegromab. Female patients who are expected to have reached reproductive maturity by the end of the trial must agree to adhere to trial-specific contraception requirements.

Exclusion criteria 9

1. El paciente suspendió permanentemente el tratamiento del estudio durante el ensayo preliminar (es decir, TOPAZ o SAPPHIRE)
2. Nutritional status that was not stable over the past 6 months and is not anticipated to be stable throughout the trial or medical necessity for a gastric/nasogastric feeding tube, where the majority of feeds are given by this route, as assessed by the investigator.
3. Patient is currently enrolled in any investigational drug trial other than TOPAZ or SAPPHIRE.
4. Prior history of severe hypersensitivity reaction or intolerance to SMN-targeted therapies.
5. Prior history of severe hypersensitivity reaction or intolerance to apitegromab.
6. Use of chronic daytime noninvasive ventilatory support for >16 hours daily in the 2 weeks before dosing, or anticipated to regularly receive such daytime ventilator support chronically throughout the trial.
7. Any acute or comorbid condition interfering with the well-being of the patient at the patient's last visit in TOPAZ or SAPPHIRE, including active systemic infection, the need for acute treatment, or inpatient observation due to any reason.
8. Pregnant or breastfeeding.
9. Any other condition or clinically significant laboratory result or ECG value that, in the opinion of the Investigator, may compromise safety or compliance, would preclude the patient from successful completion of the trial, or interfere with the interpretation of the results.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Incidence of treatment-emergent adverse event (TEAEs) and serious adverse event (SAEs) by severity

Secondary endpoints 4

1. HFMSE total score at prespecified time points (excludes TOPAZ Cohort 1 patients)
2. RULM total score at prespecified time points (excludes TOPAZ Cohort 1 patients)
3. Number of WHO motor development milestones attained at prespecified time points (excludes TOPAZ Cohort 1 patients)
4. RHS total score and results for 6-Minute Walk Test, 30-Second Sit-to-Stand, 10-Meter Walk/Run (from the RHS), and timed rise from floor (from the RHS) at prespecified time points (TOPAZ Cohort 1 patients only)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Scholar Rock Inc.

Sponsor organisation

Scholar Rock Inc.

Address

301 Binney Street

City

Cambridge

Postcode

02142-1030

Country

United States

Scientific contact point

Organisation

Scholar Rock Inc.

Contact name

Richard Riese

Public contact point

Organisation

Scholar Rock Inc.

Contact name

Richard Riese

Third parties 6

Locations

7 EU/EEA countries · 21 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 85 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

9 submissions — initial application plus substantial / non-substantial modifications