Trial Outcomes & Findings for A 12 Week Randomized Open Label Parallel Group Multicenter Study to Evaluate Bioequivalence of 20 mg Subcutaneous Ofatumumab Injected by Pre-filled Syringe or Autoinjector in Adult RMS Patients (NCT NCT03560739)

Last Updated: 2021-10-08

Results Overview

Bioequivalence of AUCtau ) will be measured over the time period of Week 8 to Week 12 dosing interval comparing the pre-filled syringe (PFS) and autoinjector (AI) devices both administered to the abdomen. Bioequivalence established if both measures meet the corresponding criterion specified by the reference-scaled average bioequivalence (RSABE) approach

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

284 participants

Primary outcome timeframe

Week 8 to Week 12 dosing interval

Results posted on

2021-10-08

Participant Flow

344 participants were screened

Participant milestones

Participant milestones
Measure	OMB 20mg AI Abdomen Ofatumumab 20 mg subcutaneous (s.c.) injection with autoinjector (AI) administrated on abdomen	OMB 20mg PFS Abdomen Ofatumumab 20 mg subcutaneous (s.c.) injection with pre-filled syringes (PFS) administrated on abdomen	OMB 20mg AI Thigh Ofatumumab 20 mg subcutaneous (s.c.) injection with autoinjector (AI) administrated on thigh	OMB 20mg PFS Thigh Ofatumumab 20 mg subcutaneous (s.c.) injection with pre-filled syringes (PFS) administrated on thigh
Overall Study STARTED	128	130	13	13
Overall Study COMPLETED	128	129	13	13
Overall Study NOT COMPLETED	0	1	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	OMB 20mg AI Abdomen Ofatumumab 20 mg subcutaneous (s.c.) injection with autoinjector (AI) administrated on abdomen	OMB 20mg PFS Abdomen Ofatumumab 20 mg subcutaneous (s.c.) injection with pre-filled syringes (PFS) administrated on abdomen	OMB 20mg AI Thigh Ofatumumab 20 mg subcutaneous (s.c.) injection with autoinjector (AI) administrated on thigh	OMB 20mg PFS Thigh Ofatumumab 20 mg subcutaneous (s.c.) injection with pre-filled syringes (PFS) administrated on thigh
Overall Study Adverse Event	0	1	0	0

Baseline Characteristics

A 12 Week Randomized Open Label Parallel Group Multicenter Study to Evaluate Bioequivalence of 20 mg Subcutaneous Ofatumumab Injected by Pre-filled Syringe or Autoinjector in Adult RMS Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	OMB 20mg AI Abdomen n=128 Participants Ofatumumab 20 mg subcutaneous (s.c.) injection with autoinjector (AI) administrated on abdomen	OMB 20mg PFS Abdomen n=130 Participants Ofatumumab 20 mg subcutaneous (s.c.) injection with pre-filled syringes (PFS) administrated on abdomen	OMB 20mg AI Thigh n=13 Participants Ofatumumab 20 mg subcutaneous (s.c.) injection with autoinjector (AI) administrated on thigh	OMB 20mg PFS Thigh n=13 Participants Ofatumumab 20 mg subcutaneous (s.c.) injection with pre-filled syringes (PFS) administrated on thigh	Total n=284 Participants Total of all reporting groups
Age, Customized 18 to 30 years	32 participants n=5 Participants	29 participants n=7 Participants	5 participants n=5 Participants	2 participants n=4 Participants	68 participants n=21 Participants
Age, Customized 31 to 40 years	42 participants n=5 Participants	53 participants n=7 Participants	3 participants n=5 Participants	10 participants n=4 Participants	108 participants n=21 Participants
Age, Customized 41 to 55 years	54 participants n=5 Participants	48 participants n=7 Participants	5 participants n=5 Participants	1 participants n=4 Participants	108 participants n=21 Participants
Sex: Female, Male Female	92 Participants n=5 Participants	90 Participants n=7 Participants	9 Participants n=5 Participants	8 Participants n=4 Participants	199 Participants n=21 Participants
Sex: Female, Male Male	36 Participants n=5 Participants	40 Participants n=7 Participants	4 Participants n=5 Participants	5 Participants n=4 Participants	85 Participants n=21 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	1 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants	1 participants n=21 Participants
Race/Ethnicity, Customized Black or African American	2 participants n=5 Participants	4 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants	6 participants n=21 Participants
Race/Ethnicity, Customized White	125 participants n=5 Participants	125 participants n=7 Participants	13 participants n=5 Participants	12 participants n=4 Participants	275 participants n=21 Participants
Race/Ethnicity, Customized Mixed	0 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants	2 participants n=21 Participants

PRIMARY outcome

Timeframe: Week 8 to Week 12 dosing interval

Population: Bio-equivalence analysis set

Outcome measures

Outcome measures
Measure	OMB 20mg AI Abdomen n=128 Participants Ofatumumab 20 mg subcutaneous (s.c.) injection with autoinjector (AI) administrated on abdomen	OMB 20mg PFS Abdomen n=128 Participants Ofatumumab 20 mg subcutaneous (s.c.) injection with pre-filled syringes (PFS) administrated on abdomen	OMB 20mg AI Thigh Ofatumumab 20 mg subcutaneous (s.c.) injection with autoinjector (AI) administrated on thigh	OMB 20mg PFS Thigh Ofatumumab 20 mg subcutaneous (s.c.) injection with pre-filled syringes (PFS) administrated on thigh
Bioequivalence of 20 mg Ofatumumab Injected by Pre-filled Syringe (PFS) vs Autoinjector (AI) to Abdomen as Measured by AUCtau	487.7 h×µg/mL Geometric Coefficient of Variation 103.5	474.1 h×µg/mL Geometric Coefficient of Variation 79.7	—	—

PRIMARY outcome

Timeframe: Week 8 to Week 12 dosing interval

Population: Bioequivalence analysis set

Bioequivalence of Cmax will be measured over the time period of Week 8 to Week 12 dosing interval comparing the pre-filled syringe (PFS) and autoinjector (AI) devices both administered to the abdomen. Bioequivalence established if both measures meet the corresponding criterion specified by the reference-scaled average bioequivalence (RSABE) approach

Outcome measures

Outcome measures
Measure	OMB 20mg AI Abdomen n=128 Participants Ofatumumab 20 mg subcutaneous (s.c.) injection with autoinjector (AI) administrated on abdomen	OMB 20mg PFS Abdomen n=128 Participants Ofatumumab 20 mg subcutaneous (s.c.) injection with pre-filled syringes (PFS) administrated on abdomen	OMB 20mg AI Thigh Ofatumumab 20 mg subcutaneous (s.c.) injection with autoinjector (AI) administrated on thigh	OMB 20mg PFS Thigh Ofatumumab 20 mg subcutaneous (s.c.) injection with pre-filled syringes (PFS) administrated on thigh
Bioequivalence of 20 mg Ofatumumab Injected by Pre-filled Syringe (PFS) vs Autoinjector (AI) to Abdomen as Measured by Cmax	1.409 µg/mL Geometric Coefficient of Variation 89.2	1.409 µg/mL Geometric Coefficient of Variation 67.9	—	—

SECONDARY outcome

Timeframe: Week 8 to Week 12 dosing interval

Population: PK analysis set

Pharmacokinetics following subcutaneous administration of ofatumumab to either the abdominal region or the thigh as measured by the area under the concentration-time curve over the Week 8 - Week 12 dosing interval (AUCtau)

Outcome measures

Outcome measures
Measure	OMB 20mg AI Abdomen n=128 Participants Ofatumumab 20 mg subcutaneous (s.c.) injection with autoinjector (AI) administrated on abdomen	OMB 20mg PFS Abdomen n=128 Participants Ofatumumab 20 mg subcutaneous (s.c.) injection with pre-filled syringes (PFS) administrated on abdomen	OMB 20mg AI Thigh n=13 Participants Ofatumumab 20 mg subcutaneous (s.c.) injection with autoinjector (AI) administrated on thigh	OMB 20mg PFS Thigh n=13 Participants Ofatumumab 20 mg subcutaneous (s.c.) injection with pre-filled syringes (PFS) administrated on thigh
Pharmacokinetics of the Study Drug as Measured by AUCtau for PFS and AI Devices When Administered to Abdomen or Thigh	487.7 h×µg/mL Geometric Coefficient of Variation 103.5	474.1 h×µg/mL Geometric Coefficient of Variation 79.7	476.0 h×µg/mL Geometric Coefficient of Variation 73.1	544.1 h×µg/mL Geometric Coefficient of Variation 93.8

SECONDARY outcome

Timeframe: Week 8 to Week 12 dosing interval

Population: PK analysis set

Pharmacokinetics following subcutaneous administration of ofatumumab to either the abdominal region or the thigh as measured by the maximum concentration (Cmax)

Outcome measures

Outcome measures
Measure	OMB 20mg AI Abdomen n=128 Participants Ofatumumab 20 mg subcutaneous (s.c.) injection with autoinjector (AI) administrated on abdomen	OMB 20mg PFS Abdomen n=128 Participants Ofatumumab 20 mg subcutaneous (s.c.) injection with pre-filled syringes (PFS) administrated on abdomen	OMB 20mg AI Thigh n=13 Participants Ofatumumab 20 mg subcutaneous (s.c.) injection with autoinjector (AI) administrated on thigh	OMB 20mg PFS Thigh n=13 Participants Ofatumumab 20 mg subcutaneous (s.c.) injection with pre-filled syringes (PFS) administrated on thigh
Pharmacokinetics of the Study Drug as Measured by Cmax for PFS and AI Devices When Administered to Abdomen or Thigh	1.409 µg/mL Geometric Coefficient of Variation 89.2	1.409 µg/mL Geometric Coefficient of Variation 67.9	1.563 µg/mL Geometric Coefficient of Variation 71.3	1.635 µg/mL Geometric Coefficient of Variation 50.7

SECONDARY outcome

Timeframe: Days 4, 7, 14, 28, 42, 56, 57, 59, 63, 70, 77, 84

Population: PK analysis set

Plasma concentrations following subcutaneous administration of ofatumumab via PFS or AI to either the abdominal region or the thigh

Outcome measures

Outcome measures
Measure	OMB 20mg AI Abdomen n=128 Participants Ofatumumab 20 mg subcutaneous (s.c.) injection with autoinjector (AI) administrated on abdomen	OMB 20mg PFS Abdomen n=130 Participants Ofatumumab 20 mg subcutaneous (s.c.) injection with pre-filled syringes (PFS) administrated on abdomen	OMB 20mg AI Thigh n=13 Participants Ofatumumab 20 mg subcutaneous (s.c.) injection with autoinjector (AI) administrated on thigh	OMB 20mg PFS Thigh n=13 Participants Ofatumumab 20 mg subcutaneous (s.c.) injection with pre-filled syringes (PFS) administrated on thigh
Plasma Concentrations of the Study Drug for PFS and AI Devices When Administered to Abdomen or Thigh EOS Week 12 n=126, 118,12,13	0.20290 µg/mL Geometric Coefficient of Variation 113.812416	0.17862 µg/mL Geometric Coefficient of Variation 102.507484	0.17361 µg/mL Geometric Coefficient of Variation 63.899086	0.27276 µg/mL Geometric Coefficient of Variation 98.256573
Plasma Concentrations of the Study Drug for PFS and AI Devices When Administered to Abdomen or Thigh Day 4 n=128,127,13,13	0.43076 µg/mL Geometric Coefficient of Variation 147.591319	0.40075 µg/mL Geometric Coefficient of Variation 119.330376	0.86747 µg/mL Geometric Coefficient of Variation 24.481350	0.55704 µg/mL Geometric Coefficient of Variation 105.432315
Plasma Concentrations of the Study Drug for PFS and AI Devices When Administered to Abdomen or Thigh Day 7 n=128, 130,13,13	0.33544 µg/mL Geometric Coefficient of Variation 133.205087	0.30511 µg/mL Geometric Coefficient of Variation 119.511321	0.36750 µg/mL Geometric Coefficient of Variation 94.007762	0.29662 µg/mL Geometric Coefficient of Variation 119.353006
Plasma Concentrations of the Study Drug for PFS and AI Devices When Administered to Abdomen or Thigh Day 14 n=128, 130,12,11	1.07408 µg/mL Geometric Coefficient of Variation 105.566707	0.96359 µg/mL Geometric Coefficient of Variation 105.735963	0.89788 µg/mL Geometric Coefficient of Variation 125.726458	1.30586 µg/mL Geometric Coefficient of Variation 83.153962
Plasma Concentrations of the Study Drug for PFS and AI Devices When Administered to Abdomen or Thigh Day 28 Week 4 n=127, 130,13,13	0.95571 µg/mL Geometric Coefficient of Variation 113.510035	0.95774 µg/mL Geometric Coefficient of Variation 117.852822	1.11008 µg/mL Geometric Coefficient of Variation 66.780045	1.41434 µg/mL Geometric Coefficient of Variation 117.959678
Plasma Concentrations of the Study Drug for PFS and AI Devices When Administered to Abdomen or Thigh Day 42 Week 6 n=128, 130,13,13	0.97327 µg/mL Geometric Coefficient of Variation 125.421064	1.12006 µg/mL Geometric Coefficient of Variation 113.137164	1.12006 µg/mL Geometric Coefficient of Variation 86.390639	1.18239 µg/mL Geometric Coefficient of Variation 133.082660
Plasma Concentrations of the Study Drug for PFS and AI Devices When Administered to Abdomen or Thigh Day 56 Week 8 n=128, 130,13,13	0.28358 µg/mL Geometric Coefficient of Variation 142.760137	0.24644 µg/mL Geometric Coefficient of Variation 133.056913	0.23874 µg/mL Geometric Coefficient of Variation 98.041287	0.45529 µg/mL Geometric Coefficient of Variation 143.614763
Plasma Concentrations of the Study Drug for PFS and AI Devices When Administered to Abdomen or Thigh Day 57 Week 8 n=127, 127,12,13	0.89424 µg/mL Geometric Coefficient of Variation 121.357310	0.80986 µg/mL Geometric Coefficient of Variation 107.929658	0.96356 µg/mL Geometric Coefficient of Variation 122.222991	1.04905 µg/mL Geometric Coefficient of Variation 54.771002
Plasma Concentrations of the Study Drug for PFS and AI Devices When Administered to Abdomen or Thigh Day 59 Week 8 n=127, 127,13,13	1.24143 µg/mL Geometric Coefficient of Variation 103.274314	1.23458 µg/mL Geometric Coefficient of Variation 81.737063	1.34837 µg/mL Geometric Coefficient of Variation 82.596695	1.52705 µg/mL Geometric Coefficient of Variation 52.253239
Plasma Concentrations of the Study Drug for PFS and AI Devices When Administered to Abdomen or Thigh Day 63 Week 9 n=126, 128,13,13	1.27031 µg/mL Geometric Coefficient of Variation 84.610014	1.23163 µg/mL Geometric Coefficient of Variation 77.294222	1.28263 µg/mL Geometric Coefficient of Variation 67.076249	1.43075 µg/mL Geometric Coefficient of Variation 66.345270
Plasma Concentrations of the Study Drug for PFS and AI Devices When Administered to Abdomen or Thigh Day 70 Week 10 n=128, 127,13,13	0.78732 µg/mL Geometric Coefficient of Variation 97.440131	0.74111 µg/mL Geometric Coefficient of Variation 82.870974	0.67151 µg/mL Geometric Coefficient of Variation 82.769087	0.95821 µg/mL Geometric Coefficient of Variation 83.645358
Plasma Concentrations of the Study Drug for PFS and AI Devices When Administered to Abdomen or Thigh Day 77 Week 11 n=127, 127,13,13	0.40249 µg/mL Geometric Coefficient of Variation 109.581877	0.33720 µg/mL Geometric Coefficient of Variation 114.373887	0.40173 µg/mL Geometric Coefficient of Variation 52.479338	0.54085 µg/mL Geometric Coefficient of Variation 97.862609
Plasma Concentrations of the Study Drug for PFS and AI Devices When Administered to Abdomen or Thigh Early Exit n=0,1,0,0	—	0.1870 µg/mL	—	—

SECONDARY outcome

Timeframe: Baseline, Week 4, 8, 12 and Overall

Population: Safety set

Anti-drug antibodies (ADA) were assessed to evaluate the immunogenicity potential of ofatumumab. Samples for ADA assessment were taken prior to dosing at the visit. Samples were analyzed as per laboratory's SOPs by a Meso Scale Discovery (MSD) electrochemiluminescense assay. All samples confirmed to be positive for the presence of anti-ofatumumab antibodies were assessed to evaluate their ability to neutralize the ofatumumab biologic effect.

Outcome measures

Outcome measures
Measure	OMB 20mg AI Abdomen n=128 Participants Ofatumumab 20 mg subcutaneous (s.c.) injection with autoinjector (AI) administrated on abdomen	OMB 20mg PFS Abdomen n=130 Participants Ofatumumab 20 mg subcutaneous (s.c.) injection with pre-filled syringes (PFS) administrated on abdomen	OMB 20mg AI Thigh n=13 Participants Ofatumumab 20 mg subcutaneous (s.c.) injection with autoinjector (AI) administrated on thigh	OMB 20mg PFS Thigh n=13 Participants Ofatumumab 20 mg subcutaneous (s.c.) injection with pre-filled syringes (PFS) administrated on thigh
Percentage of Patients With Anti-ofatumumab Antibodies Baseline n= 128,130,13,13	0.8 percentage of participants	3.1 percentage of participants	0.0 percentage of participants	7.7 percentage of participants
Percentage of Patients With Anti-ofatumumab Antibodies Week 4 n= 128,130,13,13	0.8 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Patients With Anti-ofatumumab Antibodies Week 8 n= 124,126,13,13	0.0 percentage of participants	0.8 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Patients With Anti-ofatumumab Antibodies Week 12 n= 125,121, 12,13	0.8 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Patients With Anti-ofatumumab Antibodies Overall n= 128,130,13,13	0.8 percentage of participants	3.8 percentage of participants	0.0 percentage of participants	7.7 percentage of participants

Adverse Events

OMB 20mg AI (ABD)

Serious events: 2 serious events

Other events: 61 other events

Deaths: 0 deaths

OMB 20mg PFS Abdomen

Serious events: 4 serious events

Other events: 53 other events

Deaths: 0 deaths

OMB 20mg AI (THI)

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

OMB 20mg PFS (THI)

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	OMB 20mg AI (ABD) n=128 participants at risk Ofatumumab 20 mg subcutaneous (sc.) injection with autoinjector (AI) administrated on abdomen	OMB 20mg PFS Abdomen n=130 participants at risk Ofatumumab 20 mg subcutaneous (s.c.) injection with pre-filled syringes (PFS) administrated on abdomen	OMB 20mg AI (THI) n=13 participants at risk Ofatumumab 20 mg subcutaneous (sc.) injection with autoinjector (AI) administrated on thigh	OMB 20mg PFS (THI) n=13 participants at risk Ofatumumab 20 mg subcutaneous (sc.) injection with pre-filled syringes (PFS) administrated on thigh
Ear and labyrinth disorders Vertigo	0.00% 0/128 • Adverse events were reported from first dose of study treatment until last administration of study treatment plus 100 days post treatment, up to maximum duration of 226 days	0.77% 1/130 • Adverse events were reported from first dose of study treatment until last administration of study treatment plus 100 days post treatment, up to maximum duration of 226 days	0.00% 0/13 • Adverse events were reported from first dose of study treatment until last administration of study treatment plus 100 days post treatment, up to maximum duration of 226 days	0.00% 0/13 • Adverse events were reported from first dose of study treatment until last administration of study treatment plus 100 days post treatment, up to maximum duration of 226 days
Gastrointestinal disorders Gastrointestinal motility disorder	0.78% 1/128 • Adverse events were reported from first dose of study treatment until last administration of study treatment plus 100 days post treatment, up to maximum duration of 226 days	0.00% 0/130 • Adverse events were reported from first dose of study treatment until last administration of study treatment plus 100 days post treatment, up to maximum duration of 226 days	0.00% 0/13 • Adverse events were reported from first dose of study treatment until last administration of study treatment plus 100 days post treatment, up to maximum duration of 226 days	0.00% 0/13 • Adverse events were reported from first dose of study treatment until last administration of study treatment plus 100 days post treatment, up to maximum duration of 226 days
Infections and infestations Appendicitis	0.00% 0/128 • Adverse events were reported from first dose of study treatment until last administration of study treatment plus 100 days post treatment, up to maximum duration of 226 days	0.77% 1/130 • Adverse events were reported from first dose of study treatment until last administration of study treatment plus 100 days post treatment, up to maximum duration of 226 days	0.00% 0/13 • Adverse events were reported from first dose of study treatment until last administration of study treatment plus 100 days post treatment, up to maximum duration of 226 days	0.00% 0/13 • Adverse events were reported from first dose of study treatment until last administration of study treatment plus 100 days post treatment, up to maximum duration of 226 days
Infections and infestations Pneumonia	0.00% 0/128 • Adverse events were reported from first dose of study treatment until last administration of study treatment plus 100 days post treatment, up to maximum duration of 226 days	0.77% 1/130 • Adverse events were reported from first dose of study treatment until last administration of study treatment plus 100 days post treatment, up to maximum duration of 226 days	0.00% 0/13 • Adverse events were reported from first dose of study treatment until last administration of study treatment plus 100 days post treatment, up to maximum duration of 226 days	0.00% 0/13 • Adverse events were reported from first dose of study treatment until last administration of study treatment plus 100 days post treatment, up to maximum duration of 226 days
Injury, poisoning and procedural complications Burns second degree	0.78% 1/128 • Adverse events were reported from first dose of study treatment until last administration of study treatment plus 100 days post treatment, up to maximum duration of 226 days	0.00% 0/130 • Adverse events were reported from first dose of study treatment until last administration of study treatment plus 100 days post treatment, up to maximum duration of 226 days	0.00% 0/13 • Adverse events were reported from first dose of study treatment until last administration of study treatment plus 100 days post treatment, up to maximum duration of 226 days	0.00% 0/13 • Adverse events were reported from first dose of study treatment until last administration of study treatment plus 100 days post treatment, up to maximum duration of 226 days
Reproductive system and breast disorders Menometrorrhagia	0.00% 0/128 • Adverse events were reported from first dose of study treatment until last administration of study treatment plus 100 days post treatment, up to maximum duration of 226 days	0.77% 1/130 • Adverse events were reported from first dose of study treatment until last administration of study treatment plus 100 days post treatment, up to maximum duration of 226 days	0.00% 0/13 • Adverse events were reported from first dose of study treatment until last administration of study treatment plus 100 days post treatment, up to maximum duration of 226 days	0.00% 0/13 • Adverse events were reported from first dose of study treatment until last administration of study treatment plus 100 days post treatment, up to maximum duration of 226 days

Other adverse events

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER