An Extension study of the Long-Term Safety, Tolerability, and Efficacy of DNL310 in Participants With Mucopolysaccharidosis Type II (MPS II) From Study DNLI-E-0002 or Study DNLI-E-0007

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Denali Therapeutics Inc.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

12 Dec 2023 → ongoing

Decision date (initial)

2023-11-06

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Denali Therapeutics Inc.

External identifiers

EU CT number

2023-503837-23-00

ClinicalTrials.gov

NCT06075537

ISRCTN

ISRCTN11652897

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

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

To assess the long-term safety and tolerability of DNL310 in patients with MPS II

Secondary objectives 9

1. 1.To evaluate the long term CNS activity of DNL310 as measured by the cerebrospinal fluid (CSF) concentration of heparan sulfate (HS)
2. 2. To evaluate the long-term clinical CNS efficacy of DNL310 on adaptive behavior as assessed by the Vineland-3 scale
3. 3.To evaluate the long term clinical CNS efficacy of DNL310 on adaptive behavior as assessed by the Vineland-3 Adaptive Behavior Scales, Third Edition (Vineland 3), Adaptive Behavior Composite (ABC)
4. 4.To evaluate the long term clinical CNS efficacy of DNL310 on neurocognitive development, as assessed by the Bayley Scales of Infant and Toddler Development, Third Edition (BSID III), cognitive domain
5. 5. To evaluate the long-term efficacy of DNL310 on neuronal injury in participants with nMPS II
6. 6.To evaluate the long term clinical efficacy of DNL310 on physical endurance as measured by the Six Minute Walk Test (6MWT)
7. 7.To evaluate the onset and durability of peripheral efficacy of DNL310, as measured by the urine concentration of total GAGs by mass spectrometry–based detection
8. 8.To evaluate the long term efficacy of DNL310 on liver volume and spleen volume as measured by magnetic resonance imaging (MRI)
9. 9.To evaluate the parent’s/caregiver’s assessment of long term efficacy of DNL310 as measured by the Parent/Caregiver Global Impression of Change (CaGI-C)

Conditions and MedDRA coding

Mucopolysaccharidosis Type II [MPS II]

Study design 1 period

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, European Medicines Agency, Medicines And Healthcare Products Regulatory Agency

EMA paediatric investigation plan (PIP)

EMEA-002845-PIP01-20

Plan to share IPD

No

IPD plan description

There is no plan for sharing of IPD at this time. This is consistent with what has been stated on ClinicalTrials.gov.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. • For participants from Study DNLI-E-0002 only: Completed at least through the Week 49 visit in Study DNLI-E-0002 and did not discontinue study intervention early unless the participant discontinued the study with the purpose of rolling over to Study DNLI-E-0008. • For participants from Study DNLI-E-0007 only: Completed the treatment period of 96 weeks in Cohort A for nMPS II participants and 48 weeks in Cohort B for nnMPS II participants.

Exclusion criteria 1

1. • Unstable or poorly controlled medical condition(s) or significant medical or psychological comorbidity or comorbidities that in the opinion of the investigator, would interfere with safe participation in the trial or interpretation of study assessments. • For participants who have completed E-0007 study in the open-label elaprase treatment arm.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 1. Incidence and intensity of treatment emergent adverse events (TEAEs) throughout the treatment period [Time Frame: 5 years] 2. Incidence and intensity of infusion related reactions (IRRs) throughout the treatment period [Time Frame: 5 years]

Secondary endpoints 10

1. 1.Percent change from baseline in CSF HS concentration [Time Frame: 240 weeks]
2. 2. Change from baseline in the Vineland-3 [Time Frame: 240 weeks]
3. 3.Change from baseline in the Vineland-3 ABC [Time Frame: 240 weeks]
4. 4.Change from baseline in the BSID III cognitive raw score [Time Frame: 240 weeks]
5. 5. Percent change from baseline in serum NfL [Time Frame: 240 weeks]
6. 6.Change from baseline in distance walked (meters) in the 6MWT [Time Frame: 240 weeks]
7. 7.Percent change from baseline in the sum of urine HS and dermatan sulfate concentrations [Time Frame: 240 weeks]
8. 8.Liver volume within the normal range (normal vs abnormal) as measured by MRI [Time Frame: 240 weeks]
9. 9.Spleen volume within the normal range (normal vs abnormal) as measured by MRI [Time Frame: 240 weeks]
10. 10.Improvement in CaGI C Overall MPS II (defined as much improved or a little improved) [Time Frame: 240 weeks]

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Denali Therapeutics Inc.

Sponsor organisation

Denali Therapeutics Inc.

Address

161 Oyster Point Boulevard

City

South San Francisco

Postcode

94080-2042

Country

United States

Scientific contact point

Organisation

Denali Therapeutics Inc.

Contact name

Jose Alcantara Rodriguez

Public contact point

Organisation

Denali Therapeutics Inc.

Contact name

Jose Alcantara Rodriguez

Third parties 16

Locations

8 EU/EEA countries · 12 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 109 files

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

Application history

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