A study to test Taldefgropeb Alfa in patients with Spinal Muscular Atrophy.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Biohaven Pharmaceuticals Inc.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

19 Jan 2023 → ongoing

Decision date (initial)

2024-07-16

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2024-511852-42-00

EudraCT number

2022-000193-25

ClinicalTrials.gov

NCT05337553

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To evaluate the efficacy of taldefgrobep alfa in participants who are already taking a stable regimen of nusinersen and/or risdiplam and/or have a history of onasemnogene abeparvovec-xioi, compared to placebo, measured by change in the 32 item Motor Function Measure (MFM-32) total score between Baseline and Week 48.

Secondary objectives 4

1. To compare the efficacy of taldefgrobep alfa to placebo using the Revised Upper Limb Module (RULM).
2. To compare the efficacy of taldefgrobep alfa to placebo using the Revised Hammersmith Scale (RHS).
3. To assess the safety and tolerability of taldefgrobep alfa including change from baseline in lean body mass and bone mineral density on DXA scan at Week 48, Tanner staging for puberty monitoring, new or worsening lab abnormalities, injection acceptability assessments, treatment-related adverse events (AEs), serious AEs, and AEs leading to discontinuation.
4. To assess pharmacokinetic (PK) parameters of taldefgrobep as estimated with population PK modeling.

Conditions and MedDRA coding

Spinal Muscular Atrophy

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Spinal Muscular Atrophy confirmed by genetic diagnosis of 5q-autosomal recessive SMA as well as SMN2 copy number
2. Ambulant or Non-ambulant
3. Treated with an SMA disease-modifying therapy and anticipated to remain on that same treatment regimen dose throughout the trial including nusinersen, risdiplam and/or history of onasemnogene abeparvovec

Exclusion criteria 5

1. Cannot have previously taken anti-myostatin therapies
2. Must weigh at least 15 kg
3. Respiratory insufficiency, defined by the medical necessity for invasive or non-invasive ventilation for daytime treatment while awake (use overnight or during daytime naps is acceptable).
4. History of Spinal Fusion within 6 months of Screening. MAGEC rod non-surgical adjustments are allowed during the study
5. Presence of an implanted shunt for the drainage of CSF or an implanted central nervous system (CNS) catheter

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline in the MFM-32 at Week 48

Secondary endpoints 4

1. Change from baseline in the RULM at Week 48
2. Change from baseline in the RHS at Week 48
3. Safety and tolerability assessments including change in lean body mass and bone mineral density on DXA scan from baseline at Week 48 and Tanner staging for puberty monitoring, monitoring of injection acceptability assessments, and frequency of unique subjects with: new or worsening lab abnormalities, treatment related adverse events, serious adverse events, and adverse events leading to discontinuation.
4. Trough plasma concentrations of taldefgrobep alfa and pharmacokinetic parameters estimated with population PK modeling

Investigational products

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

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Biohaven Pharmaceuticals Inc.

Sponsor organisation

Biohaven Pharmaceuticals Inc.

Address

215 Church Street

City

New Haven

Postcode

06510-1803

Country

United States

Scientific contact point

Organisation

Biohaven Pharmaceuticals Inc.

Contact name

Lia Donahue

Public contact point

Organisation

Biohaven Pharmaceuticals Inc.

Contact name

Chief Compliance Officer

Third parties 14

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Serious breaches 1 · Art. 52 CTR

Results and documents

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

Documents 333 files

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

Application history

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