NIMBLE: A Study to Examine the Efficacy and Safety of Pozelimab and Cemdisiran Combination Therapy in Adult Patients With Symptomatic Generalized Myasthenia Gravis

Sponsor

Regeneron Pharmaceuticals (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05070858

Collaborator

(none)

235

Enrollment

Locations

Arms

64.5

Anticipated Duration (Months)

8.7

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary objective is:

To evaluate the effect of pozelimab + cemdisiran on daily functioning that is impacted by signs and symptoms in patients with symptomatic generalized myasthenia gravis (gMG)

The secondary objectives of the study are:

To evaluate the effect of pozelimab + cemdisiran (ie, combination) and cemdisiran monotherapy on:
Clinician-assessed signs of myasthenia gravis (MG) and muscle strength
Daily functioning that is impacted by signs and symptoms in patients with symptomatic gMG (cemdisiran monotherapy only).
Proportion of patients with improvements in daily function that is impacted by signs and symptoms of MG
Proportion of patients that have improvements in clinician-assessed signs of MG and muscle strength
Health related quality of life
Proportion of patients with minimal MG symptoms
Patient- and clinician-reported signs and symptoms of MG
To evaluate the safety and tolerability of pozelimab + cemdisiran and cemdisiran monotherapy
To assess the concentration of total pozelimab in serum
To assess the concentrations of cemdisiran and its metabolites in plasma
To assess the immunogenicity of pozelimab
To assess the concentration of total C5 in plasma
To assess the immunogenicity of cemdisiran
To study the effect of pozelimab + cemdisiran and cemdisiran monotherapy on complement activation

Condition or Disease	Intervention/Treatment	Phase
Generalized Myasthenia Gravis	Drug: Pozelimab + Cemdisiran Drug: Cemdisiran Other: Placebo Drug: Pozelimab	Phase 3

Detailed Description

DBTP- Double blind treatment plan (24 weeks) ETP - Extension treatment plan (28 weeks) OLTP- Open label treatment plan (68 weeks) Off-treatment follow up period (52 weeks)

Study Design

Study Type:

Interventional

Anticipated Enrollment :

235 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Efficacy and Safety of Pozelimab and Cemdisiran Combination Therapy in Patients With Symptomatic Generalized Myasthenia Gravis

Actual Study Start Date :

Dec 14, 2021

Anticipated Primary Completion Date :

Aug 14, 2024

Anticipated Study Completion Date :

May 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group 1 Placebo in DBTP; Re-randomized to Combination or Cemdisiran in ETP and OLTP	Drug: Pozelimab + Cemdisiran Subcutaneous administration as described in the protocol Drug: Cemdisiran SC administration as described in the protocol Other Names: ALN-CC5 Other: Placebo SC administration as described in the protocol
Experimental: Group 2 Combination regimen throughout the study	Drug: Pozelimab + Cemdisiran Subcutaneous administration as described in the protocol
Experimental: Group 3 Cemdisiran throughout the study	Drug: Cemdisiran SC administration as described in the protocol Other Names: ALN-CC5
Experimental: Group 4 Pozelimab monotherapy in DBTP followed by combination in ETP and OLTP	Drug: Pozelimab SC administration as described in the protocol Other Names: REGN3918

Outcome Measures

Primary Outcome Measures

Change in Myasthenia Gravis-Activities of Daily Living (MG-ADL) total score [From baseline to week 24]
The total MG-ADL score ranges from 0 to 24 points, with higher scores indicating greater functional impairment and disability

Secondary Outcome Measures

Change from baseline in Quantitative Myasthenia Gravis (QMG) score [Week 24]
QMG total scores range from 0 to 39, with higher scores representing greater impairment
Proportion of patients responding on the MG-ADL [From baseline to week 24]
≥3-point improvement
Proportion of patients responding on the QMG [From baseline to week 24]
≥5-point improvement
Proportion of patients with consistent response on the MG-ADL [From baseline to week 24]
At least a 2-point MG-ADL improvement on 2 or more consecutive assessments spanning 4 or more weeks during the DBTP
Proportion of patients with minimal symptom expression (MSE) [Week 24]
Score of 0 to 1 on the MG-ADL
Change from baseline in the Myasthenia Gravis Composite (MGC) total score [Week 24]
MGC score ranges from 0 to 50, with higher score indicating higher impairment
Change from baseline in Myasthenia Gravis Quality of Life (MG QOL15r) total score [Week 24]
Total score ranges from 0 to 30 points; a higher score represents greater impairment
Proportion of patients with improvement point thresholds on MG-ADL [From baseline to week 24]
≥2, 4, 5, 6, 7, 8, 9, or 10
Proportion of patients with improvement point thresholds on QMG [From baseline to week 24]
≥3, 4, 6, 7, 8, 9, or 10
Incidence and severity of treatment-related adverse events (TEAEs) in patients treated with pozelimab + cemdisiran or placebo [Through week 24]
Incidence and severity of serious adverse events (SAEs) in patients treated with pozelimab + cemdisiran or placebo [Through week 24]
Incidence and severity of adverse events of special interest (AESIs) in patients treated with pozelimab + cemdisiran or placebo [Through week 24]
Concentrations of total pozelimab in serum [Through study duration, approximate 172 weeks]
Concentrations of cemdisiran and its metabolites in plasma [Through study duration, approximate 172 weeks]
Incidence of treatment-emergent anti-drug antibodies (ADAs) to pozelimab over time [Through study duration, approximately 172 weeks]
Incidence of treatment-emergent ADAs to cemdisiran over time [Through study duration, approximate 172 weeks]
Change in CH50 over time [Through study duration, approximately 172 weeks]
Percent change in CH50 over time [Through study duration, approximately 172 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key Inclusion Criteria:

Male or female patients ≥18 years of age at screening (or ≥ legal age of adulthood based on local regulations, whichever is older)
Patient with documented diagnosis of myasthenia gravis (MG) based on medical history and supported by previous evaluations as described in the protocol
Documented prior history of positive serologic test or a positive result during screening of anti-acetylcholine receptor (AChR) antibodies or anti-LRP4 antibodies.
Myasthenia Gravis Foundation of America (MGFA) Clinical Classification Class II to IVa at screening
Myasthenia Gravis-Activities of Daily Living (MG-ADL) score ≥6 at screening. Ocular items should not contribute more than 50% of MG-ADL total score
Currently receiving an acetylcholinesterase inhibitor or documented reason for not using acetylcholinesterase inhibitor therapy per investigator 7. Currently receiving an immunosuppressive therapy (IST) for MG, or documented reason why the patient is not taking an IST per investigator
If currently receiving an IST, not anticipated to have IST dosage changed before randomization or during double-blind treatment period (DBTP).

Key Exclusion Criteria:

Patients with antibody profile that is only positive for muscle specific tyrosine kinase (MuSK) (MuSK positivity is based on a documented prior history of positive serologic test for antibodies to MuSK or a positive result during screening
History of thymectomy within 12 months prior to screening or planned during the study
History of malignant thymoma (patients with stage 1 may be enrolled), or history of cancer within the past 5 years, except for adequately treated basal cell skin cancer, squamous cell skin cancer, or in situ cervical cancer
Myasthenic crisis or Myasthenia Gravis Foundation of America (MGFA) Class V within 1 month of screening
No documented meningococcal vaccination within 5 years prior to screening visit unless vaccination will be administered during the screening period and prior to initiation of study treatment
Known contraindication to meningococcal vaccines (group ACWY conjugate and group B vaccines) as described in the protocol
Patients who require antibiotics for meningococcal prophylaxis and have a contraindication, warning, or precaution precluding the use of penicillin class and penicillin-alternative antibiotics planned to be used for prophylaxis, or a history of intolerance leading to the discontinuation of these antibiotics
Positive hepatitis B surface antigen or hepatitis C virus ribonucleic acid (RNA) during screening. NOTE: Cases with unclear interpretation should be discussed with the medical monitor
History of HIV infection or a positive test at screening per local requirements

NOTE: Other protocol-defined Inclusion/ Exclusion Criteria apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California, Irvine	Irvine	California	United States	92868
2	University of Southern California	Los Angeles	California	United States	90033
3	Colorado Springs Neurological Associates	Colorado Springs	Colorado	United States	80907-5307
4	SFM Clinical Research, LLC	Boca Raton	Florida	United States	33487-5712
5	Collier Neurologic Specialists LLC	Naples	Florida	United States	34105-8523
6	Neurological Services of Orlando	Orlando	Florida	United States	32806-6264
7	Medsol Clinical Research Center Inc	Port Charlotte	Florida	United States	33952
8	Northwestern University	Chicago	Illinois	United States	60611
9	NorthShore University Health System	Evanston	Illinois	United States	60201-3137
10	Prairie Education and Research Cooperative	O'Fallon	Illinois	United States	62269
11	Northwest Neurology Ltd. - Clinedge - PPDS	Rolling Meadows	Illinois	United States	60008-3154
12	University Of Cincinnati Gardner Neuroscience institute	Cincinnati	Ohio	United States	45219
13	Austin Neuromuscular Center	Austin	Texas	United States	78759
14	Nerve and Muscle Center of Texas	Houston	Texas	United States	77030
15	St Vincents Hospital Melbourne	Fitzroy	Victoria	Australia	3065
16	UZ Antwerpen	Edegem	Antwerpen	Belgium	2650
17	AZ Sint-Lucas	Gent	Oost-Vlaanderen	Belgium	9000
18	Universita' Degli Studi La Sapienza	Roma	Lazio	Italy	00185
19	Azienda Ospedaliera Sant'andrea	Roma	Lazio	Italy	00189
20	Fondazione IRCCS Di Rilievo Nazionale Istituto Nazionale Neurologico Carlo Besta	Milano	Lombardia	Italy	20133
21	Samsung Medical Center - PPDS	Seoul		Korea, Republic of	03722
22	Centrum Neurologii Klinicznej, Krakowska Akademia Neurologii	Kraków	Malopolskie	Poland	31-505
23	Gdanski Uniwersytet Medyczny	Gdansk	Pomorskie	Poland	80-952
24	Hospital Universitario La Paz - PPDS	Madrid		Spain	28046
25	China Medical University Hospital	Taichung		Taiwan	404
26	National Cheng Kung University Hospital	Tainan City		Taiwan	701
27	Shin Kong Wu Ho Su Memorial Hospital	Taipei		Taiwan	111

Sponsors and Collaborators

Regeneron Pharmaceuticals

Investigators

Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Regeneron Pharmaceuticals

ClinicalTrials.gov Identifier:

NCT05070858

Other Study ID Numbers:

R3918-MG-2018
2020-003272-41

First Posted:

Oct 7, 2021

Last Update Posted:

Aug 16, 2022

Last Verified:

Aug 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Myasthenia Gravis

Muscle Weakness

Study Results

No Results Posted as of Aug 16, 2022